Showing papers on "HER2/neu published in 2006"

Akt is frequently activated in HER2/neu-positive breast cancers and associated with poor prognosis among hormone-treated patients

Abstract: Akt/PKB is a serine/threonine kinase that plays an important role in survival when cells are exposed to different apoptotic stimuli. Aberrant activation of Akt/PKB in breast carcinoma is associated with poor prognosis and resistance to endocrine therapy and chemotherapy. The Akt signaling pathway currently attracts considerable attention as a new target for effective therapeutic strategies. We therefore investigated the relationship between activation of Akt and clinicopathologic variables including hormone receptor and HER2/neu status. Breast cancer tissues obtained from 252 patients were utilized for this study. We evaluated Akt activation by immunohistochemical assessment of the expression of phosphorylated Akt (pAkt) at Ser-473. Eighty-four cases (33.3%) were diagnosed as positive for pAkt expression. pAkt was significantly associated with HER2/neu overexpression (p < 0.0001). There was an inverse correlation between pAkt and PR expression (p = 0.0321); however, there was no association between pAkt and ER expression. Survival analysis showed that pAkt positivity was associated with poor disease-free survival in cases with postoperative hormone therapy; however, there was no association in cases without hormone therapy. Our results indicate that Akt activation induced poor prognosis in patients who received adjuvant hormone therapy. This finding suggests that inhibition of the Akt signaling pathway may increase the efficacy of hormone therapy and improve the prognosis of patients who receive adjuvant hormone therapy.

p130Cas as a New Regulator of Mammary Epithelial Cell Proliferation, Survival, and HER2-Neu Oncogene–Dependent Breast Tumorigenesis

Abstract: To investigate the mechanisms through which p130Cas adaptor protein is linked to tumorigenesis, we generated mouse mammary tumor virus (MMTV)-p130Cas mice overexpressing p130Cas in the mammary gland. MMTVp130Cas transgenic mice are characterized by extensive mammary epithelial hyperplasia during development and pregnancy and by delayed involution at the end of lactation. These phenotypes are associated with activation of Src kinase, extracellular signal-regulated kinase 1/2, mitogen-activated protein kinase, and Akt pathways, leading to an increased rate of proliferation and a decreased apoptosis. A double-transgenic line derived from crossing MMTV-p130Cas with MMTV-HER2-Neu mice expressing the activated form of the HER2-Neu oncogene develops multifocal mammary tumors with a significantly shorter latency than the HER2-Neu parental strain alone. Mammary epithelial cells isolated from tumors of double-transgenic mice display increased tyrosine phosphorylation, c-Src, and Akt activation compared with cells derived from HER2-Neu tumors. In addition, p130Cas down-regulation by RNA interference increases apoptosis in HER2-Neu-expressing cells, indicating that p130Cas regulates cell survival. Consistently with the double-transgenic mice model, p130Cas is overexpressed in a significant subset of human breast cancers and high levels of p130Cas in association with HER2 expression correlate with elevated proliferation. These findings provide evidences for a role of p130Cas as a positive regulator of both proliferation and survival in normal and transformed mammary epithelial cells. Its overexpression contributes to HER2-Neu-induced breast tumorigenesis, thus identifying this protein as a putative target for clinical therapy.

Evaluation of the HER2/neu-derived peptide GP2 for use in a peptide-based breast cancer vaccine trial.

Abstract: BACKGROUND E75 and GP2 are human leukocyte antigen (HLA)-A2-restricted immunogenic peptides derived from the HER2/neu protein. In a E75 peptide-based vaccine trial, preexisting immunity and epitope spreading to GP2 was detected. The purpose of this study was to further investigate GP2 for potential use in vaccination strategies. Importantly, a naturally occurring polymorphism (I V at position 2, 2VGP2) associated with increased breast cancer risk was addressed. METHODS Prevaccination peripheral blood samples (PBMC) from HLA-A2 breast cancer patients and CD8+ T cells from HLA-A2 healthy donors were stimulated with autologous dendritic cells (DC) pulsed with GP2 and tested in standard cytotoxicity assays with HER2/neu+ tumor cells or GP2- or 2VGP2-loaded T2 targets. Additional cytotoxicity experiments used effectors stimulated with DC pulsed with E75, GP2, or the combination of E75+GP2. RESULTS GP2-stimulated prevaccination PBMC from 28 patients demonstrated killing of MCF-7, SKOV3-A2, and the HLA-A2− control target SKOV3 of 28.8 ± 3.7% (P<.01), 29.5 ± 4.0% (P<.01), and 16.9 ± 2.7%, respectively. When compared with E75, GP2-stimulated CD8+ T cells lysed HER2/neu+ targets at 43.8 ± 5.2% versus 44.2 ± 5.7% for E75 (P = .87). When combined, an additive effect was noted with 58.6 ± 5.4% lysis (P = .05). GP2-stimulated CD8+ T cells specifically recognized both GP2-loaded (19.6 ± 5.7%) and 2VGP2-loaded T2 targets (17.7 ± 5.2%). CONCLUSIONS GP2 is a clinically relevant HER2/neu-derived peptide with immunogenicity comparable to that of E75. Importantly, GP2-specific effectors recognize 2VGP2-expressing targets; therefore, a GP2 vaccine should be effective in patients carrying this polymorphism. GP2 may be most beneficial used in a multiepitope vaccine. Cancer 2006. Published 2006 by the American Cancer Society.

Investigating the Combination of Trastuzumab and HER2/neu Peptide Vaccines for the Treatment of Breast Cancer

Abstract: Background Trastuzumab, an anti-HER2/neu monoclonal antibody, is thought to promote HER2/neu receptor internalization and/or turnover. This study was designed to investigate the kinetics of trastuzumab treatment on tumor cells with varying levels of HER2/neu expression and to determine the effect of trastuzumab on HER2/neu-specific cytotoxic T lymphocyte–mediated lysis.

Human T Cells Armed with Her2/neu Bispecific Antibodies Divide, Are Cytotoxic, and Secrete Cytokines with Repeated Stimulation

Abstract: Purpose: Cancer immunotherapy has been limited by anergy of patient T cells, inadequate numbers of precursor tumor-specific CTL, and difficulty in producing therapeutic doses of CTL. To overcome these limitations, bispecific antibodies have been used to create artificial antibody receptors that direct polyclonal activated T cells (ATC) to target tumor antigens. Studies reported herein were designed to characterize bispecific antibody–armed ATC functions during multiple rounds of targeted cell stimulation. Experimental Design: ATCs were generated from human peripheral blood mononuclear cells (PBMC) by culture with anti-CD3 and interleukin 2 for 14 days and armed with anti-CD3 × anti-Her2 bispecific antibody (Her2Bi). In vitro , Her2Bi-armed ATC were examined for a range of functions after repeated stimulation with the Her2/ neu -expressing breast cancer cell line SK-BR-3. PBMC isolated from cancer patients treated with Her2Bi-armed ATC were tested ex vivo for cytotoxicity against SK-BR-3. Results: In vitro , armed ATC divided, maintained surface Her2Bi, and expressed a range of activities for extended periods of time. Perforin-mediated cytotoxic activity by armed ATC continued for at least 336 hours, and cytokines and chemokines (i.e., IFN-γ and regulated on activation, normal T-cell expressed and secreted protein [RANTES]) were secreted during successive rounds of stimulation. Furthermore, PBMC isolated from patients over their courses of immunotherapy exhibited significant cytolytic activity against SK-BR-3 as a function of Her2Bi-armed ATC infusions. Conclusions: These studies show that armed ATC are specific, durable, and highly functional T-cell populations in vitro . These previously unappreciated broad and long-term functions of armed ATC are encouraging for their therapeutic use in treating cancer.

Phase II study of lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase 1 and 2 (Her2/Neu) in patients (pts) with advanced biliary tree cancer (BTC) or hepatocellular cancer (HCC). A California Consortium (CCC-P) Trial

Abstract: 4010 Background: Advanced BTC (gallbladder, bile duct) and HCC respond poorly to systemic chemotherapy. Lapatinib is an oral inhibitor of EGFR and Her/2-neu with evidence of activity in a number of...

A Herpes Simplex Virus Recombinant That Exhibits a Single-Chain Antibody to HER2/neu Enters Cells through the Mammary Tumor Receptor, Independently of the gD Receptors

Abstract: The human epidermal growth factor receptor 2/neuregulin (HER2/neu) receptor is overexpressed in highly malignant mammary and ovarian tumors and correlates with a poor prognosis. It is a target for therapy; humanized monoclonal antibodies to HER2 have led to increased survival of patients with HER2/neu-positive breast cancer. As a first step in the design of an oncolytic herpes simplex virus able to selectively infect HER2/neu-positive cells, we constructed two recombinants, R-LM11 and R-LM11L, that carry a single-chain antibody (scFv) against HER2 inserted at residue 24 of gD. The inserts were 247 or 256 amino acids long, and the size of the gD ectodomain was almost doubled by the insertion. We report the following. R-LM11 and R-LM11L infected derivatives of receptor-negative J or CHO cells that expressed HER2/neu as the sole receptor. Entry was dependent on HER2/neu, since it was inhibited in a dose-dependent manner by monoclonal antibodies to HER2/neu and by a soluble form of the receptor. The scFv insertion in gD disrupted the ability of the virus to enter cells through HVEM but maintained the ability to enter through nectin1. This report provides proof of principle that gD can tolerate fusion to a heterologous protein almost as large as the gD ectodomain itself without loss of profusion activity. Because the number of scFv's to a variety of receptors is continually increasing, this report makes possible the specific targeting of herpes simplex virus to a large collection of cell surface molecules for both oncolytic activity and visualization of tumor cells.

HER2/neu expression and gene alterations in pancreatic ductal adenocarcinoma: a comparative immunohistochemistry and chromogenic in situ hybridization study based on tissue microarrays and computerized image analysis

Abstract: Context HER2/neu overexpression is observed in many cancers including pancreatic ductal adenocarcinoma Although immunohistochemistry remains the basic method for evaluating HER2/neu protein expression, significant information regarding gene status cannot be assessed Design Using tissue microarray technology, fifty histologically confirmed pancreatic ductal adenocarcinomas were cored twice and re-embedded in one paraffin block Immunohistochemistry (clone TAB 250) and chromogenic (HER2/neu amplification Spot Light kit) in situ hybridization protocols were performed The immunostained slides were evaluated by conventional eye microscopy and digital image analysis The chi square test and the kappa statistic were applied by running the SPSS package Main outcome measures :The levels of staining intensity were estimated by the performance of a semi automated image analysis system Results HER2/neu gene amplification was detected in 8/50 cases (16%) Chromosome 17 aneuploidy was detected in 19 cases (38%) Significant improvement in interobserver agreement (kappa=076 vs 094) was achieved correlating the immunohistochemical results obtained by conventional eye and digital microscopy, especially in the cases of overexpression (2+, 3+) Finally, 29 (58%), 11 (22%), 6 (12%) and 4 (8%) cases were characterized as 0, 1+, 2+ and 3+, respectively HER2/neu protein expression was significantly associated with grade (P=0019), but not with stage (P=0466) in addition, chromosome 17 and gene status were not correlated with stage and grade Conclusion Our results indicate that a subset of pancreatic ductal adenocarcinomas is characterized by HER2/neu gene amplification In contrast to breast cancer, protein overexpression does not predict this specific gene deregulation mechanism This event may reflect the different biological role of the molecule in those two solid tumours, affecting the response to novel targeted agents, such as monoclonal anti-HER2/neu antibodies Furthermore, evaluation of HER2/neu protein expression based on digital image analysis and not only on conventional eye microscopy improves the accuracy and reliability of immunohistochemical estimation, although that does not demonstrate clinical significance and prognostic value in pancreatic ductal adenocarcinoma

Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine.

Abstract: We are conducting clinical trials in breast cancer (BrCa) patients to test the HER2/neu peptide vaccine (E75). We have investigated the impact of this vaccine on circulating levels of regulatory T cells (Treg) and the resulting effects on antitumor responses. Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2+ patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry. Cytotoxic activity against HER2/neu + tumors was measured by 51Cr-release. Serum from BrCa patients and normal subjects were analyzed for TGF-β levels. BrCa patients have a greater percentage of circulating Treg (CD4+CD25+, 4.45% versus 2.96%; p = 0.007) than normal subjects. HLA-A2+ BrCa patients had more Treg compared to the HLA-A2– BrCa patients (CD4+CD25+, 5.63% versus 3.28%; p = 0.001). E75 vaccination increased circulating activated CD4+ T cells post-vaccination (CD4+CD69+, 1.23 versus 3.81%; p = 0.03). However, Treg were significantly reduced after vaccination (CD4+CD25+, 5.31–1.81%; p < 0.0001). Furthermore, activated Treg also decreased (CD4+CD25+CD69+, 0.23% versus 0.08%; p = 0.06). Importantly, post-vaccination decreases in Treg were temporally associated with increased E75 vaccine-specific CD8+ T cells and corresponding HER2/neu + tumor cytotoxicity. Serum TGF-β levels were significantly elevated in BrCa patients compared to normals (3548 pg/ml versus 1007 pg/ml; p = 0.007). Four of seven vaccinated patients showed decreased serum TGF-β levels post-vaccination. Treg, are increased in BrCa patients along with serum levels of TGF-β. E75 vaccination resulted in CD4+ recruitment but was associated with a significant decrease in circulating Treg and TGF-β levels in the majority of the vaccinated patients. Successful cancer vaccination strategies may require the alteration of complex immune interactions.

Expression and possible prognostic role of MAGE-A4, NY-ESO-1, and HER-2 antigens in women with relapsing invasive ductal breast cancer: retrospective immunohistochemical study.

Abstract: Breast cancer is the most common malignancy in women (1). Its clinical course may vary from indolent and slowly progressive to rapidly metastatic disease. Identification of prognostic and predictive factors that reflect the biology of breast cancer is important for the assessment of prognosis and selection of patients who may benefit from adjuvant and/or systemic therapy. The important aspects of prognostic factors suitable for clinical use are their availability, reproducibility, and cost. In routine clinical practice, treatment decisions and selection of treatment modalities for each individual patient are based on the standard prognostic factors, such as age (1,2), menopausal status (3), tumor size (1-4), tumor grade (3-5), steroid-hormone receptor status (1-5), and nodal metastases (1-5). Variability in clinical course of breast cancer is partly related to tumor cell growth rate and other features, such as invasiveness or metastatic potential. Research in molecular biology has identified genes and their products involved in or associated with the malignant cell transformation and behavior. Moreover, expression of some of these molecules, such as p53 (1,6,7), Ki-67 (7,8), nm23 (1,7), catepsin D (1,7), Ep-CAM (9,10), HER-2 (1,2,6), and urokinase-type plasminogen activator and its inhibitor (1,11), is associated with the patient’s prognosis. As it seems that many genes and molecules might be involved in malignant transformation and cell behavior, other additional molecules may also be tested as potential prognostic factors. The cancer/testis (C/T) genes encode tumor-associated antigens (TAA) found in various tumors of different histological origin, but not in normal tissues other than testis (12,13). Their physiological function is unknown. Peptides derived from these antigens could be used as targets in active immunotherapy. Analysis of the expression of these genes or their products in malignancies could also be of potential diagnostic and/or prognostic relevance (14,15). Therefore, we performed a retrospective analysis of immunohistochemical expression of C/T antigens MAGE-A4 and NY-ESO 1 in women with invasive breast cancer. We also analyzed the expression of HER-2 antigen, because it has a prognostic and predictive role (1,16).

Prevalence of hormone receptors and HER2/neu in breast cancer cases in Jordan

Abstract: The management and prognosis of breast cancer nowadays require the evaluation of Estrogen (ER), Progesterone Receptors (PR) and HER2/neu Ethnic variation in the expression of these receptors is well documented The aim of this study is to determine the prevalence of ER, PR and HER2/neu among Jordanian women with breast cancer of ductal and lobular types A retrospective analysis was performed on 267 cases of breast cancer referred for treatment at King Hussein Cancer Center, Jordan between the period of June 2003 and June 2004 Standard immune stains were used for evaluation of hormone receptors and HER2/neu In addition, evaluation of HER2/neu was done by FISH in selected cases Of these 267 cases, 240 (899%) were ductal carcinomas of various histological grades, 122 (508%) of which were ER-positive, 138 (575%) PRpositive and 42 (175%) HER2/neu-positive Twentytwo (82%) of all cases were lobular carcinomas, 15 (68%) of which were ER-positive, 20 (909%) PRpositive and 3 (136%) HER2/neu-positive Five (19%) of the total cases were of mixed lobular and ductal types, 4 (80%) of which were ER-positive, 3 (60%) PR-positive and none were positive for HER2/neu The prevalence of hormone receptor positivity in breast cancer of Jordanian women is lower than that of the western populations and close to other populations such as the Chinese and the minor ethnic groups of Northern America (African Americans)

A trimeric anti-HER2/neu ScFv and tumor necrosis factor-alpha fusion protein induces HER2/neu signaling and facilitates repair of injured epithelia.

Abstract: Tumor necrosis factor (TNF)-α genetically fused to the carboxyl terminus of a single-chain Fv (ScFv) antibody specific for the human HER2/ neu (anti-HER2/ neu ScFv-TNF-α) forms a homotrimeric structure that retains both TNF-α activity and the ability to bind HER2/ neu . In contrast to anti-HER2/ neu IgG3, anti-HER2/ neu ScFv-TNF-α induces potent HER2/ neu signaling, activating the downstream mitogen-activated protein kinase (MAPK) and Akt pathways in SKBR3 cells. Activation of MAPK and Akt by anti-HER2/ neu ScFv-TNF-α inhibited the apoptosis of SKBR3 cells induced by actinomycin D. Remarkably, anti-HER2/ neu ScFv-TNF-α facilitated the repair of injured epithelia. Accelerated wound healing required binding to HER2/ neu but not TNF-α activity since anti-HER2/ neu ScFv-TNF-α (S147Y), containing a mutant TNF-α with significantly decreased biological activity, demonstrated equivalent ability to facilitate wound healing and soluble HER2/ neu inhibited the effect. These results suggest that trimeric anti-HER2/ neu ScFv has the potential to facilitate wound healing. In addition, fusion with TNF-α provides a novel approach to producing polymeric antibodies.

Correlation between HER2/neu overexpression/amplification and clinicopathologic parameters in advanced gastric cancer (AGC) patients (pts): A prospective study

Abstract: 4089 Background: Trastuzumab is widely used in the treatment of HER2/neu overexpressing breast cancer pts and also exhibits activity in human gastric cancer cells that overexpress HER2/neu. We are ...

Cytokines fused to antibodies and their combinations as therapeutic agents against different peritoneal HER2/neu expressing tumors

Abstract: We have previously generated antihuman HER2/neu-humanized IgG3 fused to interleukin-2 (IL-2), IL-12, or granulocyte macrophage colony-stimulating factor (GM-CSF) [monofunctional fusion proteins (mono-AbFP)] or fused to IL-2 and IL-12 or IL-12 and GM-CSF [bifunctional fusion proteins (bi-AbFP)]. These AbFPs retained cytokine and antigen-binding activities. We have now further characterized the AbFPs and determined the heparin-binding activity of the fused cytokines, their ability to trigger IFN-gamma secretion and natural killer (NK) activation, and their direct antitumor efficacy. Flow cytometry revealed heparin-binding activity in the AbFPs containing IL-12 and IL-2, although this activity seems to be decreased in the bi-AbFPs. However, both bi-AbFPs retained the capacity to stimulate IL-12-dependent IFN-gamma secretion in the NK cell line KY-1, and IL-12/IL-2 bi-AbFP induced NK activity in splenocytes. The antitumor effectiveness of bi-AbFPs and mono-AbFP combinations was studied in mice challenged i.p. with three different human HER2/neu murine syngeneic models (D2F2/E2, CT26-HER2/neu, and MC38-HER2/neu). Although a significant variability in the profile of antitumor response was observed in the different tumor models, the combination of IL-12 and GM-CSF mono-AbFPs protected 100% of D2F2/E2-challenged and 75% of CT26-HER2/neu-challenged mice. In contrast, bi-AbFPs protected less than the combination of mono-AbFPs and, in some models, even less than mono-AbFPs alone. However, in all cases, most of long-term survivors showed protection after s.c. rechallenge with the tumors and later with the parental tumors not expressing HER2/neu. These results show that, although the pattern of protection is tumor model dependent, treatments with AbFPs can effectively generate high levels of protection against peritoneal tumors expressing HER2/neu, which may be relevant in patients with primary or metastatic peritoneal carcinomatosis that may be observed in ovarian, colon, stomach, bladder, lung, and breast cancers.

p53 and HER2/neu expression in relation to chemotherapy response in patients with non-small cell lung cancer

Abstract: The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.

Expression of wild-type estrogen receptor β protein in human breast cancer: Specific correlation with HER2/neu overexpression

Abstract: Expression of estrogen receptor beta (ERbeta) protein in human breast cancer and correlation with clinicopathological factors have been reported by many investigators, but many of them used ERbeta antibodies that react with both wild-type ERbeta (ERbetawt) and splicing variant isoform. Therefore, the frequency and correlation with clinicopathological factors of ERbetawt expression remain to be established. In the present study a monoclonal antibody EMR02, specific for ERbetawt, was used in formalin-fixed paraffin-embedded sections from 225 female primary breast cancer patients diagnosed as having invasive ductal carcinoma. Expression of ERalpha, progesterone receptor (PgR) and HER2/neu were also investigated by immunohistochemistry. For ERbetawt, ERalpha and PgR, positivity was defined as nuclear staining in >10% of the cancer cells. HER2/neu overexpression was defined as a Hercep test score 3+. Positivity for ERbetawt, ERalpha, PgR and HER2/neu overexpression was 55%, 74%, 61% and 25%, respectively. The expression of ERbetawt had a positive correlation with ERalpha (P=0.018) and PgR (P=0.02). There was significant positive correlation between ERbetawt expression and HER2/neu overexpression (P<0.0001). According to multivariate logistic regression analysis the most significant association was between ERbetawt expression and HER2/neu overexpression (P<0.0001). These results suggest that clinical significances of ERbetawt expression in human breast cancer patients may be more complex.

Glassy cell carcinoma of the cervix: cytologic features and expression of estrogen receptor, progesterone receptor and Her2/neu protein

Abstract: Objective To analyze the cytologic features, estrogen and progesterone receptors, and Her2/neu protein in glassy cell carcinoma (GCC) of the cervix. Study design Cases were analyzed using various parameters, including age at presentation, stage, treatment and clinical course. Between 1990 and 2003, patients with primary cervical carcinomas were treated and cytopathologic analyses performed. Tests for estrogen receptor (ER), progesterone receptor (PR) and Her2/neu protein were performed on paraffin sections. Results GCC of the cervix is composed of large cells with abundant chromatin, which gives them their characteristic glassy appearance. Eleven cases were identified as GCC. One case (9.1%) was correctly diagnosed from the cervicovaginal smear. Among the GCC cases, ER, PR and Her2/neu were positive in 2 (18.1%), 1 (9.1%) and 5 (45.4%) cases, respectively. Conclusion Cytology of GCC reveals characteristic features that differ from those of other carcinomas of the cervix. GCC has unique cytologic characteristics and causes diagnostic confusion, possibly leading to incorrect diagnoses. The reason for such low diagnostic precision in cytology might be due to the lack of differentiation and low frequency of this tumor. Our results, demonstrating Her2/ neu overexpression, may correlate with more aggressive behavior and a worse clinical outcome.

HER2/neu expression in relation to clinicopathologic features of breast cancer patients.

Abstract: : We have evaluated HER2/neu expression in 1,355 breast cancer patients recruited at the Breast Cancer Registry in Palermo between January 1999 and December 2004. In this retrospective study, HER2/neu expression was related to clinicopathologic features of the disease, including tumor size, nodal and menopausal status, estrogen and progesterone receptors. Statistical analysis on all 1,355 patients showed a significant correlation between HER2/neu and nodal status (P < 0.001), and a significant association between HER2/neu overexpression and estrogen and progesterone receptors status (P < 0.001). In 194 patients without metastasis, with an average follow-up ≥5 years, only HER2/neu 3+ and histopathologic grading G3 were significantly associated with overall survival.