Showing papers on "HER2/neu published in 2020"

Treatment Strategies and Survival Outcomes in Breast Cancer.

Abstract: Treatment strategies for breast cancer are wide-ranging and often based on a multi-modality approach, depending on the stage and biology of the tumour and the acceptance and tolerance of the patient [...].

Investigation of the combination of anti-PD-L1 mAb with HER2/neu-loaded dendritic cells and QS-21 saponin adjuvant: effect against HER2 positive breast cancer in mice

Abstract: Human epidermal growth factor receptor 2 (HER2) is overexpressed in a subset of cancers including 25% of breast cancers. Since combination therapy consisting of multiple therapeutic approaches is c...

Immunohistochemical Expression of BRCA1 Protein, ER, PR and Her2/neu in Breast Cancer: A Clinicopathological Study.

Abstract: Breast cancer is a heterogeneous hormone-dependent disease. Potential prognosis depends on the clinicopathological evaluation and assessment of other prognostic indicators. The detection of the oestrogen Receptor (ER), Progesterone Receptor (PR), Human epidermal growth factor receptor 2 (Her2/neu) and BRCA1 oncoprotein is pivotal for prognostic evaluation and to choose the appropriate post-surgical adjuvant therapy beside selecting the proper candidate for genetic counselling. Objectives To detect the immunoexpression of the BRCA1 oncoprotein in mammary invasive ducal carcinoma and its association with the prognostic markers (ER, PR and Her2/neu hormonal receptors) and other clinicopathological parameters to improve the patients' treatment plans. Methods A cross-sectional study design including 83 paraffin blocks and histological slides collected from Al-Jumhoori Medical City Teaching Hospital Laboratory in Mosul and the Central Public Health Laboratory in Baghdad between the 1st of January 2010 to the 13th of March 2012 for patients diagnosed with primary invasive ductal breast carcinomas. Immunohistochemistry (IHC) using monoclonal antibodies against ER, PR, Her2/neu receptors and BRCA1 protein was performed via the fully automated immunostaining instrument 'Ventana Benchmark'. Results BRCA1 protein immunoexpression was detected in 20.5% of cases. It was significantly high with increasing tumour grade and stage. Although there was a trend of BRCA1 negativity toward negative ER, PR and Her2 receptors, no significant associations were observed with any of these parameters and the patients' age. Conclusion Altered BRCA1 expression is significantly associated with advanced tumour grade and stage. High number of cases with negative BRCA1 expression showed negative ER, PR and Her2/neu expression.

Preparation of nanoliposomes containing HER2/neu (P5+435) peptide and evaluation of their immune responses and anti-tumoral effects as a prophylactic vaccine against breast cancer.

Abstract: HER2/neu is an immunogenic protein inducing both humoral and cell-mediated immune responses. The antigen-specific cytotoxic T lymphocytes (CTLs) are the main effector immune cells in the anti-tumor immunity. To induce an effective CTL specific response against P5+435 single peptide derived from rat HER2/neu oncogene, we used a liposome delivery vehicle. In vivo enhancement of liposome stability and intracytoplasmic delivery of peptides are the main strategies which elevate the liposome-mediated drug delivery. Liposomes containing high transition temperature phospholipids, such as DSPC, are stable with prolonged in vivo circulation and more accessibility to the immune system. Incorporation of DOPE phospholipid results in the effective delivery of peptide into the cytoplasm via the endocytotic pathway. To this end, the P5+435 peptide was linked to Maleimide-PEG2000-DSPE and coupled on the surface of nanoliposomes containing DSPC: DSPG: Cholesterol with/without DOPE. We observed that mice vaccinated with Lip-DOPE-P5+435 formulation had the highest number of IFN-γ- producing CTLs with the highest cytotoxic activity that consequently led to significantly smallest tumor size and prolonged survival rate in the TUBO mice model. In conclusion, our study indicated that the liposomal form of P5+435 peptide containing DOPE can be regarded as a promising prophylactic anti-cancer vaccine to generate potent antigen-specific immunity.

Progression-Free Survival and Overall Survival in Patients with Advanced HER2-Positive Breast Cancer Treated with Trastuzumab Emtansine (T-DM1) after Previous Treatment with Pertuzumab.

Abstract: The approval of trastuzumab emtansine (T-DM1) was conducted without pertuzumab as previous therapy. Efficacy data on T-DM1 following pertuzumab treatment are therefore limited. This study explores this issue in a real-world setting. Within the prospective PRAEGNANT (Prospective Academic Translational Research Network for the Optimization of the Oncological Health Care Quality in the Advanced Setting) metastatic breast cancer registry (NCT02338167), patients in all therapy lines receiving any kind of treatment were eligible for inclusion. This report describes patient characteristics and progression-free survival (PFS) in human epidermal growth factor receptor 2 (HER2)-positive patients receiving T-DM1 after pertuzumab treatment. Seventy-six patients were identified, 39 of whom received T-DM1 as second-line therapy, 25 as third-line, and 12 as fourth-line therapy or higher. Pertuzumab was mostly administered as a first-line treatment (n = 61; 80.3%). The median PFS in all patients was 3.5 months (95% CI: 2.8-7.8); in second-line treatment, 7.7 months (95% CI: 2.8-11.0); in third-line, 3.4 months (95% CI: 2.3-not reached (NR)); and in fourth-line therapy or higher, 2.7 months (95% CI: 1.2-NR). T-DM1 was mainly administered second-line after pertuzumab, but also in more heavily pretreated patients. The PFS in higher therapy lines appears to be shorter than in second-line.

Human epidermal growth factor receptor 2 (Her2) testing for uterine serous carcinoma: Report of scenarios of unusual overexpression.

Abstract: The human epidermal growth factor receptor 2 (Her2) is tested in many human cancers, including breast, bladder, pancreatic, ovarian and stomach. The American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) have issued Clinical Practice Guidelines for reporting Her2 results for breast carcinomas ( Wolf et al., 2018 ). For the last 1–2 years Her2/neu is tested in endometrial serous carcinoma, especially in recurrent tumors or non-responsive tumors as an option for additional treatment. College of American Pathologists (CAP) offers a template for prognostic marker reporting results for specimens with endometrial carcinomas ( Fitzgibbons et al., 2019 ). Her2/neu testing by immunohistochemistry (IHC) mandates rigorous fixation time control, e.g., fixation time should fall within 6–72 h ( Recommendations for Her2 Testing in Breast Cancer, 2013 ). For that reason, in breast cancers, Her2/neu testing is done on initial core biopsy specimens. The test is however, repeated on excision specimen in high grade tumors where Her2/neu expression was initially negative on core biopsies. For endometrial serous carcinoma no guidelines have been set or proposed as of yet. The Gynecologic Oncologists request this test because of proven benefit of adding Trastuzumab ( Fader et al., 2018 ) and that is why it is important to documenting the findings in this report in the literature so that an informed request can be made by the treating oncologist when multiple tissue samples from the same patient are available for testing. Similarly pathologists also can decide which would be the best sample to test when no instruction is received. We report here three separate scenarios of uterine serous carcinomas in which the Her2/neu expressions were unique enough to justify documentation and therefore have implications for determining which specimen is ideal for the Her2 overexpression testing and likely to have highest possibility in identifying the Her2/neu overexpressed clone in the tumor which would expand the therapeutic options for the patients.

Quantitative real-time PCR assay with immunohistochemical evaluation of HER2/neu oncogene in breast cancer patients and its correlation with clinicopathological findings.

Abstract: Human epidermal growth factor receptor HER2/neu status is an important prognostic factor for breast cancer as it is crucial in stimulating growth and cellular motility. Overexpression of HER2/neu is observed in 10%-35% of the human breast cancer and is associated with prognosis and response to treatment. The magnitude of amplification must be determined to facilitate better prognosis and personalized therapy in the affected patient. This study aims to investigate the HER2/neu status in breast cancer by concurrent HER2/neu protein overexpression immunohistochemically with HER2/neu DNA amplification by quantitative real-time polymerase chain reaction (PCR), allowing accurate and precise quantification of HER2/neu amplification after a follow-up period. A total of 54 paired tissue samples from formalin-fixed paraffin-embedded (FFPE) breast cancer patients enrolled in this study were collected to evaluate tumor and normal tissues. Only cases with 80% and more tumor cells were included. For confirmation of immunohistochemistry (IHC) results, qPCR was used to determine the HER2/neu amplification. The association between clinicopathological variables like age, tumor size, histological grade, stage, lymph node status, hormone receptor status, family history, recurrence rate, and vital status was evaluated. We observed that 11/54 (20.4%) of the tumor tissues are positive for HER2/neu protein overexpression by IHC. A total of 8 out of these 11 cases (72.7%), which presented a score of 3+, showed gene amplification of HER2/neu. The concordance rate between IHC and qPCR was 94.4%. HER2/neu gene amplification was found to be significantly associated with recurrence, increased risk of death, and progesterone receptor status, supporting a negative prognostic role of HER2/neu in breast cancer survival. In conclusion, IHC can be used as an initial screening test to detect HER2/neu protein overexpression, and the use of qPCR can verify the IHC results and establish HER2/neu status in routine clinical practice.

The Effects of Low HER2/neu Expression on the Clinicopathological Characteristics of Triple-Negative Breast Cancer Patients.

Abstract: Background Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer (BC), and its diagnosis is associated with negative expression of hormone receptors and HER2/neu. It consists of 10-20% of all BCs diagnosed. Methods and materials This study focuses on three groups with different pathology: group one showed complete triple-negative HER2 expression with IHC of BC; groups two and three included patients with ER-, PR-, and HER21+, and ER-, PR-, and HER22+ with a negative FISH test. These three groups were compared from the point of prognosis, which consisted of tumor size, patients' age, lymphatic, vascular and perineural invasion, organ metastasis, number of lymph nodes involvement, and the survival rate. Results A total of 459 TNBC patients were enrolled, of which 268 were placed in the HER20 group, 146 in the HER21+ group, and 45 in the HER22+ group. Distant metastasis and recurrence rate were more common in HER20 patients, but bone metastasis was more common in patients with low HER2 expression. All patients with HER20 had a smaller tumor size at the time of BC diagnosis in comparison to patients in the low HER2 expression group. Patients with HER22+ had less lymphatic and vascular invasion as well as axillary lymph nodes involvement, but larger tumor size at presentation, resulting in a lower rate of recurrence and higher overall survival. Conclusion The findings revealed that patients with HER22+ had better outcome in comparison to the patients with HER20 and HER21+. Furthermore, the results showed that many patients with HER22+ expression were not basal-like and had good prognosis amongst TNBC patients.

HER2/neu Oncogene and Sensitivity to the DNA-Interactive Drug Doxorubicin

Abstract: Breast tumor cells overexpressing the proto-oncogene HER2/neu are known to be less responsive to certain DNA-binding chemotherapeutic agents. The current study specifically investigates the correlation between chemosensitivity to the DNA-binding drug doxorubicin and cellular HER2/neu protein levels in a panel of eight breast cancer cell lines (HS-578, BT-474, MDA-MB-453, MDA-MB-231, MDA-MB-175, MCF-7, ZR-75-1 and T47D). The IC50 (the drug concentration required to inhibit cell growth by 50%) values for the cell lines were determined by the sulforhodamine B assay. IC50 values were correlated with HER2/neu protein levels determined by Western blotting. An almost linear relationship between IC50 and HER2/neu protein level for seven cell lines (p = 0.02, r2 = 0.680) was found, with protein levels increasing as resistance increased. The findings suggest that overexpression of HER2/neu correlates with increased resistance to doxorubicin in seven of eight breast cancer cell lines studied. The observation that, in one cell line (MDA-MB-175), doxorubicin IC50 did not correlate with HER2/neu levels, suggests that in these cells, an as-of-yet unidentified factor contributes to resistance. If the observed correlation, which was present in seven of eight cell lines, is confirmed in a larger sample size, increased HER2/neu levels may be implemented as a predictor of breast tumor sensitivity to doxorubicin.

Clinicopathological significance of immunohistochemical expression of Filamin A in breast cancer.

Abstract: BACKGROUND: Filamin A is an actin-crosslinking protein expressed in many malignancies, although its prognostic and therapeutic role in breast cancer is not studied. There is enigma regarding its dual role in cancer, the tumor-progressing or tumor-suppressing effects depending on the site to which it localizes in the cell. The current study aimed to detect Filamin A expression in breast cancer and its association with other biomarkers and other clinicopathological parameters and established risk factors in breast cancer so that it can be a potential site for targeted therapy. MATERIALS AND METHODS: One hundred female patients of histologically proven breast cancer who presented to our hospital over a 2-year period were included in the study. None of the patients received prior radiotherapy, chemotherapy, or immunotherapy. Patients with recurrent breast cancer are not included in the study. All study cases are subjected to immunohistochemistry for estrogen receptor, progesterone receptor, Her2 neu, and ki-67 from core biopsy tissue of cases diagnosed as breast carcinoma. Tissue sections were subjected to immunohistochemistry with anti-Filamin A. RESULTS: Filamin A is expressed in 69% of cases of invasive breast cancer in our study. There was no statistically significant relationship of Filamin A immunoexpression with histological grade, age, parity, oral contraceptive use, smokeless tobacco use, TNM staging, clinical staging, clinical prognostic staging, and also ER, PR, Her2 neu, and ki-67 status (P > 0.05). Thus, it appears to be an independent biomarker in breast carcinoma. Filamin A was expressed only in the cytoplasm in all our study cases. Filamin A expression can be observed in adjacent normal breast tissue and benign fibroadenoma tissues also, but the pattern of expression is mainly membranous with cytoplasmic positivity. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. CONCLUSION: No significant correlation could be found between Filamin A expression and clinicopathological parameters in our study. The cytoplasmic expression is seen in malignant cells as well as normal breast and benign tumor sections implicating the dual role of Filamin A in breast cancer. Filamin A immunoexpression should be further correlated with metastasis-free survival period of breast cancer patients

Selection of HER2/NEU negative tumor cells as a mechanism of resistance to trastuzumab in uterine serous carcinoma.

Abstract: Background Uterine serous carcinoma (USC) is an aggressive variant of endometrial cancer overexpressing HER2/neu in about 30% of cases. Trastuzumab, a humanized monoclonal antibody targeting Her2/Neu, in combination with carboplatin/paclitaxel, is considered the preferred regimen for the treatment of advanced or recurrent HER2/Neu+ USC per NCCN guidelines. Case We describe two USC patients with overexpression of HER2/neu at 2+/3+ level by immunohistochemistry and c-erbB2 gene amplification by fluorescence in situ hybridization (FISH) assay that, after an initial clinical response to trastuzumab, developed resistance/progression. Post-treatment biopsy (collected at the time of clinical progression on trastuzumab) demonstrated loss of HER2/neu overexpression in the recurrent/progressing tumor cells in both patients. Conclusion Selection of HER2/NEU negative tumor cells may represent a major mechanism of resistance to trastuzumab in USC patients.

HER2/neu expression in gastric carcinoma and its association with Helicobacter pylori infection and other clinicopathological parameters

Abstract: Background: Gastric cancer is the 5th most common malignancy and 3rd leading cause of cancer death worldwide. Most cases are diagnosed in advanced stages making treatment difficult. International regulatory agencies have recently approved trastuzumab therapy in locally advanced and metastatic gastric adenocarcinomas expressing HER2. Aims: To find HER2/neu expression in adenocarcinoma of stomach and correlate with clinicopathological features and study H.pylori positivity in HER2 positive cases. Settings and Design: The ambispective, observational study was conducted in the department of Pathology (July 2017 to June 2019). Materials and Methods: Seventy eight cases of gastric adenocarcinoma were studied, both endoscopy guided biopsy or gastrectomy. Expression of HER2/neu and detection of Helicobacter pylori was done using immunohistochemistry. HER2 expression was correlated with clinicopathological parameters and H.pylori infection. Statistical Analysis used: Fisher’s exact test, chi square test and p value Results: HER2/neu was positive in 26.92% of cases, 16.67% were equivocal and 56.41% were negative. 55.13% of intestinal type were HER2 positive. Grade 1 tumor showed more HER2 positivity (42.31%). HER2 positivity was independent of other parameters like age, sex and location of tumor. H.pylori was positive in 24.36% of HER2/neu positive cases. Conclusions: HER2 positivity correlated with Lauren’s intestinal type and grade 1 of tumor.HER2 is an independent biomarker regardless of other clinicopathological features. Though few Her2 positive cases showed H. pylori positivity, more larger studies are required to establish statistically significant association between HER2 positivity and H.pylori infection. Keywords: Gastric cancer, Helicobacter pylori, HER2/neu.

AE36 HER2/neu-derived Peptide Linked to Positively Charged Liposomes with CpG-ODN as an Effective Therapeutic and Prophylactic Vaccine for Breast Cancer

Abstract: In the present day and age, cancer is still a life-limiting factor whose one of the therapeutic strategies is immunotherapy with vaccines. This research aims to prepare and characterize nanoliposomal vaccine formulation attached to HER2/neu-derived peptide (AE36) with or without CpG-ODN, and to evaluate its immunological responses to the therapy using BALB/c mice with HER2 overexpressing breast cancer. Methods: AE36 was conjugated to the liposomes containing DOTAP, DOPE and Cholesterol. Such formulations are able to produce CD8+ and CD4+ responses and induce synthesis of cytokines detectable via Enzyme-linked immunosorbent assay kits, cytotoxicity testing and intracellular cytokine staining combined with flow cytometry. Therapeutic and prophylactic effectiveness were evaluated through the formulation in samples. The highest effectiveness was found in DDC-peptide + CpG-ODN in both prophylactic and therapeutic studies, which decreased the size of tumors significantly and increased time of survival. These nanoliposomes linked to AE36 could be regarded as an appropriate candidate for the treatment and also for prophylaxis of HER2+ breast cancer; however further studies are needed.

A Prospective Study on Level of Concordance Between Core Needle Biopsy and Surgical Specimen for Assessing Oestrogen Receptor, Progesterone Receptor, and Her2/Neu Receptor Status in Carcinoma Breast and Its Implications on Treatment Decisions.

Abstract: A prospective study on the level of concordance between core needle biopsy specimen (CNB) and surgical specimen (SS) assesses the oestrogen receptor (ER), progesterone receptor (PR) and Her2/Neu receptor status in Carcinoma breast and its implications on treatment decisions Ninety consecutive treatment naive operable breast cancer patients treated between September 2015 and April 2017 were included in our prospective study All patients underwent core needle biopsy prior to definitive surgery Immunohistochemistry (IHC) studies for ER, PR, and Her2/Neu receptor assay were done in both the CNB specimen and SS The concordances between CNB specimen and SS for ER, PR, and Her2/Neu receptor were 92%, 88%, and 78% respectively In our study, overall discordance for ER, PR, and Her2/Neu status based on IHC tests on CNB specimen and its corresponding SS was 41% (37 out of total 90 patients), which was mostly for Her2/Neu (20 patients) Altogether, there was a change in treatment decision based on IHC test results of CNB specimen for 14 out of 37 discordant tests, translating to 15% of the overall study group Four patients received adjuvant hormonal therapy, and 10 patients got adjuvant Traztuzumab added to their protocol There is almost perfect to substantial concordance between CNB specimen and SS of IHC tests for ER and PR status However, the concordance for Her2/Neu receptor is only moderate Her2/Neu receptor assay by IHC is more sensitive in CNB specimen than in SS

Predictor of trastuzumab-induced cardiotoxicity in breast cancer (BC) patients: HER2/neu 655 polymorphisms, biochemical and clinical features.

Abstract: 1033Background: The introduction of trastuzumab in the treatment scheme of the HER2 BC patients has improved the evolution of the disease. Nevertheless, some of this patients develop cardiotoxicity...

Pertuzumab-associated diarrhea in HER2/neu-positive breast cancer patients: A comparison of trials to actual practice:

Abstract: BackgroundAlthough landmark trials in the metastatic (CLEOPATRA) and neo-adjuvant (NeoSphere; TRYPHAENA) settings identified all-grade diarrhea as a pertuzumab-associated adverse event, it was not ...

Frequency of overexpression of Her2/neu in colorectal adenocarcinomas– A hospital based cross-sectional study

Abstract: Introduction: Colorectal malignancies stand out to be one of the chief causes of morbidity and mortality in the world. Although the total incidence of colorectal malignancy in India n population has marginally increased, it is now a common cause of cancer mortality among Indians. The oncogene HER2/neu belongs to the tyrosine kinase receptor family. The favorable outcome of HER2/neu in management of breast carcinoma patients has direct ed to evaluation of gene amplification protein overexpression, and anti-tumor activity of Herceptin in various tumor types one amongst which is colorectal carcinomas. The objective of the study was to evaluate the frequency of overexpression of HER2/neu in colorectal adenocarcinomas (CRC) and its association with various histomorphological and clinicopathological parameters. Materials and Methods: A total of 52 cases of colorectal adenocarcinomas including colonoscopic biopsies & resected specimens were studied. Paraffin embedded sections were stained with Hematoxylin & Eosin and histological and clinicopathological parameters were assessed. In IHC, antigens were retrieved by Heat Induced Epitope Retrieval method and HER2/ neu status was determined using a semiquantitative scoring system. The scores were then correlated with histological grade, type and clinicopathological parameters. Results: The HER2/neu overexpression was noted in 53.8% of our cases and was seen to be commonly expressed by moderately differentiated tumours and conventional/ NOS histological type. There was a statistically significant correlation observed between HER2/neu status and tumour grade (p= 0.001), tumour type (p = 0.008). There was no significant correlation between age, gender or localisation or stage of tumour. Conclusion: Histological grade and histological type of CRC showed a significant correlation with HER2/neu overexpression, hence can be used as a predictive tool for determining the prognosis of the patients. Patients who overexpress HER2/neu could

Immunohistochemical Expression of Ki-67, p53 and HER2/neu in Meningiomas

Abstract: Introduction: Meningiomas are one of the most common primary intracranial tumours. Although most meningiomas are benign, the spectrum also includes atypical and malignant meningiomas. Clinical outcome of meningiomas is often difficult to predict. The stratification of risk on the basis of histomorphology alone remains problematic; thus additional biomarkers are needed. In this study biomarkers of prognostic and therapeutic interest like Ki-67, p53 and HER2/neu have been studied in correlation with clinicopathological parameters. Materials and methods: A retrospective study on histologically diagnosed meningiomas was undertaken. Slides were retrieved and reviewed. Clinical details were recorded from the files in the archives of the department. Immunohistochemical staining with markers Ki-67, p53 and HER2/neu were performed and the findings were interpreted. Results: The study included 17 cases with an age range of 16 to 73 years and a male: female ratio of 1.1:1.There were 11 cases (64.7%) of primary tumours and 6 cases (35.3%) were recurrent tumours. WHO Grade I meningiomas were maximum and accounted for 70.5% followed by grade II (17.5%) and grade III (12%) meningiomas. Ki-67 expression was seen in all cases with progressively increased expression in higher grades. p53 expression was observed in all the cases with higher levels (>10%) in Grade II and Grade III meningiomas compared to grade I meningiomas. The HER2/neu staining was negative in all cases studied. Conclusion: Grade I meningiomas appear to have low mitotic count on morphology but have higher proliferation rate on Ki-67 studies. Most of the recurrent tumours have higher p53 expression (>10%). Hence, adjuvant studies with biomarkers Ki-67 and p53 will be helpful in precise grading of meningiomas.

A study of histomorphology and immunohistochemical profile in breast cancer in a tertiary care hospital

Abstract: The most common cancer among women in the urban Indian population is breast cancer and it is second only to cancer of the cervix in the rural population. Breast cancer is no longer seen as a single disease but rather a multifaceted disease comprised of distinct biological subtypes with diverse natural history, presenting a varied spectrum of clinical, pathologic and molecular features with different prognostic and therapeutic implications. One important aspect of the role of Pathology in the evaluation of breast cancer is biomarker testing, specifically the accurate assessment of the Estrogen receptor (ER), progesterone receptor (PR), and Her2 neu status of a patient's breast cancer. Biomarkers can be prognostic, predictive, or both. Prognostic biomarkers are independent measures of prognosis such that the presence or absence of the biomarker is associated with a patient's overall clinical outcome.

WT1, Bcl-2, Ki-67 and Her2/Neu as diagnostic and prognostic immuno markers in ovarian serous and endometrioid carcinoma

Abstract: Background: Ovarian cancer is the fifth common cause of death due to cancer in women. It constitutes 3% of all cancers in females and 15-20% of genital malignancies. Most of the ovarian cancers are serous type followed by endometrioid type. Sometimes glands of these two carcinomas are indistinguishable histologically. It also becomes difficult to differentiate these two types when they are poorly differentiated. Aims: The aim of this study was to find out differences in immuno-markers expressions between serous and endometrioid carcinomas and association of their staining patterns with other clinico-pathological prognostic factors. Materials and Methods: Immunohistochemical staining for WT1, Bcl2, Ki67 (MIB1) and Her2/Neu were done in paraffin embedded tissues of histologically diagnosed total 38 cases (21 serous and 17 endometrioid) of ovarian carcinomas and staining patterns were correlated with other clinico-pathological prognostic factors. Results: Out of these 38 cases, 24 cases were in stage I/II (early stage) and 14 cases stage III/IV (advance stage). On the other hand, 16 cases were low grade, 12 cases intermediate grade and 10 cases high grade. Twenty out of 21 serous carcinomas were positive for WT1, whereas most of the endometrioid carcinomas were negative. Ki67 labeling index and Her2/Neu were higher in both higher grade and stages. On the contrary, intensity of Bcl2 staining was lower in higher grades and stages lesions.Conclusions: Use of WT1 may be useful in resolving diagnostic dilemma between serous and endometrioid carcinoma, especially in difficult cases. Ki67, Bcl2 and Her2/Neu may be used as prognostic markers.

Histopathological spectrum of lower Gastro-intestinal colonoscopic biopsy lesion with special reference to Her-2/neu expression in carcinoma colon

Abstract: Cancer associated with colon is one of the principal risk factors from decease in women and men. Although importance growing aspect of human epidermis receptor2 (Her2) as a therapeutic target is rising its role as a biomarker in the form of predicting indicator within colorectal Cancer (CRC)is still a mystery. Present research is undertaken for evaluating the Her2/neu description in Cancer of the colon. This research comprises 256patientswith spectrum of histopathological treatment ranging from colitis to colorectal carcinoma at our department between 2015- 2017. Her2/neu Immunohistochemistry was done in the colorectal carcinoma and scores based on Ruschoff et al. Her-2 testing in gastric cancer. Out of a total number of 256 cases enrolled in our study group, the majority belonged to the age group of 40-60 years, with M: F ratio being 1.4:1. The commonest site of the lesion occurred in the rectum (43.75%) followed by ascending colon and caecum (12.08%). Non neoplastic lesions constituted about two third of all cases, the commonest being inflammatory bowel disease(21.48%). In benign neoplastic lesions of tubular adenoma was the commonest type, and in malignant commonest type was colorectal adenocarcinoma NOS(64.44%) followed by mucinous adenocarcinoma (22.22%). Because of more prominent membranous staining observed in high grade colorectal cancers, Her2neu expression is found to be an important predictive marker of carcinoma colon, especially the adenocarcinoma, NOS. Like Breast carcinoma, target oriented therapy can be instituted especially in Her 2/neu positive high grade and metastatic tumors.

A Study Comparing Histopathological Grade of Breast Carcinoma with Her2/Neu Status in a Tertiary Care Hospital

Abstract: Introduction: Breast cancer is a leading cause of concern in today’s medical care and newer diagnostic tools like immunohistochemistry have been frequently implemented in diagnostic efforts in addition to the existing histopathological findings. It is important to see how these two diagnostic modalities show up as a whole and in relation to each other. Through this study, we make an effort to accomplish just the same. Aims and Objectives: To look at the observations and comparative findings of histopathological grade and immunohistochemical (HER2/neu) markers and find any correlation that may be of help to future studies. Materials and Methods: A sample of 50 patients with Invasive breast ca were observed and their histopathological grades (Nottingham scoring) were sent along with immunohistochemistry done (HER2/neu). Results and noted and tallied with each other. Results: It was observed that there were maximum cases of grade 2 followed by 3 and then 1. Also that there were more HER2/neu negative cases than positive. Also that the frequency of HER2/neu positivity was more in grade 1 yet quantity of cases of HER2/neu positivity turned out to be more in grade 2. Conclusion: It would be very helpful to keep a close eye on even lower grades of Breast carcinoma as they would have a high chance of HER2/neu positivity and thus poor prognosis.

Profile of HER2/neu, Estrogen Receptor and Heat Shock Protein 27 Expression in Early And Late Onset Indonesian Breast Cancer Patients

Abstract: Introduction: Early onset breast cancer (occuring under age 40) tend to exhibit a different, aggressive phenotype, and are usually associated with hereditary BRCA1 or BRCA2 mutations. We investigated the levels of Hsp27 and HER2/Neu, as well as ER positivity, in early onset breast cancer patients. Materials and methods: Eighteen paraffin blocks of tissues from patients diagnosed with invasive ductal carcinoma of no specific type (IDC-NST) regardless of grade or stage, age below 39 years (mean 34 years) who underwent surgery or surgical biopsy in Dr. Soetomo General Hospital, Surabaya, within the period of January 2014 - December 2014, were examined for Hsp27 expression, estrogen receptor status, and HER2/Neu amplification. The control group consisted of blocks from 112 patients diagnosed with IDC-NST aged older than 40 who underwent resection within the same period; all specimen in the control group is also stained for Hsp27 and tested for ER and HER2/Neu status. Results: Examined blocks gained from the younger patient pool typically has higher grade, were negative for estrogen receptor status and show less Hsp27 expression. Sixteen (88.9%) of early-onset patients has grade II or III cancer, with 55.55% presenting with grade III cancer. Meanwhile, 79 (70.53%) of late onset patient has grade II or III cancer, with 26.78% presenting with grade III cancer. Seventy-seven out of 112 (68.75%) patients aged 50 or older has positive ER status, while only 8 out of 18 (45.45%) of early-onset patients have positive ER status. All patients aged 50 years and below show Hsp27 score that is less than the median score, while from all patients aged 50 or above, 64 out of 96 (66.66%) samples exceed the median score. Meanwhile, HER2/Neu scoring distribution seem to be similar across age groups. Conclusion: Difference in estrogen receptor expression and Hsp27 levels show a significant difference between early-onset and late-onset breast cancer patients. Meanwhile, HER2/Neu amplicafication shows similarities between early-onset and late-onset patients.

Clinicopathological and immunohistological profile of infiltrating ductal carcinoma breast in a tertiary care centre of western UP- A study of 100 cases

Abstract: Introduction: Breast cancer is the most common cause of death of women worldwide and it is the most common malignancy in Indian females followed by carcinoma cervix. Diagnosis involves various modalities like clinical examination, radiological investigations, fine needle aspiration cytology (FNAC) and histopathological examination. Recently, immunohistochemistry (IHC), is becoming a standard methodology in pathology laboratories worldwide. IHC provides substantial information with regard to diagnosis, therapeutic prediction and prognosis of breast cancer. Therefore, hormonal studies evaluating the status of estrogen receptor (ER), progesterone receptor (PR) and Human epidermal growth factor-2 (Her2 neu) have become a part and parcel of the histopathology reporting. Materials and Methods: Present study included 100 cases of Infiltrating Ductal Carcinoma (IDC) breast diagnosed in mastectomy specimens received in department to Pathology, Rohilkhand Medical College and Hospital, Bareilly between July 2014 to June 2017. Other histological variants were excluded from the study. Various parameters including age, site, tumor size, lymph node metastasis, histopathological grading, hormone receptor status namely ER, PR and Her2 neu were studied. The histological grade was correlated with the hormone receptor status. Results: Majority patients belonged to the age group of 41-50 years (34%). Most of the carcinomas were of Bloom Richardson grade II (73%). In terms of the IHC profile, majority were ER/PR negative and Her2 neu positive (45%). Conclusion: Breast carcinoma should be studied in all respects in order to understand its behaviour. Additionally, immunohistopathological studies should be carried out in all cases in order to obtain predictive and prognostic information. Keywords: Breast Carcinoma, Grade, Hormone receptor, Bloom Richardson.

A study of Estrogen Receptor, Progestrone Receptor and hER2/NEU expressions in cases of breast cancer in a tertiary care hospital

Abstract: The study of Estrogen receptor, Progesterone receptor and HER-2/neu expressions in cases of ca breast was carried out over a period of 2 years at tertiary care hospital karad which included 101 breast cancer cases. Maximum numbers of patients (34.65%) were in the 41 – 50 years group. All patients were female. Family history was seen in 10 (9.90%) cases. Out of 101 cases equal cases were in the category of invasive breast carcinoma grade -II (46.42%) and grade- III (46.42%).While grade- I tumors comprised of 7.41% cases. Invasive breast carcinoma - no special type accounted for maximum cases (77.22%). Other histological types were medullary carcinoma (7.92%), mucinous carcinoma (2.97%). Out of 101 cases, 56.43% of breast cancer cases were positive for estrogen and progesterone receptors. Maximum number of HER-2/neu over expression 5/10 (50%) was seen in 41-50 years of age group.A positive correlation was found between ER and PR expression. Maximum number of triple negative cases were seen in medullary carcinoma (100%), metaplastic carcinoma (100%) followed by invasive breast carcinoma .Out of 101 cases of breast cancer, 42 cases (41.58%) showed axillary lymph node metastasis. Axillary metastasis was divided as 0 lymph node (no metastasis) - 58.41% cases, 1-3 lymph node metastasis – 21.78% and >3 lymph node metastasis – 19.80%. Tumor emboli were noted in 31.68% of cases. Estrogen and Progesterone receptor expression correlate well with the established prognostic markers like- age, type of tumor, histological grade, axillary lymph node metastasis and tumor emboli.

HER2/neu Expression in Gastrointestinal Carcinoma Among South Indians

Abstract: Background: HER2/neu oncogene overexpression and amplification in breast cancer is well known. Studies have proved its role in gastric cancer and its correlation with the prognosis. Very few studies are there in literature regarding HER2/neu expression in entire gastrointestinal carcinoma. Our study was aimed at HER2/neu expression in gastrointestinal tumors in South Indian Population. M ethods: We included all patients with gastrointestinal carcinoma who either underwent biopsy or surgical excision over the past five years. Slides were reviewed for confirmation of the diagnosis and immunohistochemistry was done using SP3 monoclonal anti-HER2 antibodies. Three independent observers did the scoring for HER2 positivity. Results: Among 35 cases of gastric cancer, only 2 (5.7%) females showed positivity for HER2 scoring and one (2.9%) female showed an equivocal result. All positive and equivocal cases in gastric cancer were intestinal type. Both the cases with HER2 positivity were poorly differentiated tumors. The one with equivocal was a moderately differentiated carcinoma. In colorectal cancer out of 19 cases, only one (5.3%) showed positivity for HER2 whereas in one there was an equivocal response. All the seven cases of small intestinal carcinoma showed negative results for HER2 expression. Conclusion: Overall, HER2/neu expression in gastrointestinal cancer was 4.9%. Female gender, intestinal- type and poorly differentiated cancer showed positivity in gastric cancer. Female gender, left side and low-grade tumor showed positivity in colorectal cancer. Further studies are required with a large sample size to correlate HER2 expression with clinicopathological parameters and its role in prognosis in gastrointestinal carcinomas in the Indian population.