Showing papers on "Large cell published in 2003"

Lung cancer screening with CT: Mayo Clinic experience

Abstract: PURPOSE: To evaluate a large cohort of patients at high risk for lung cancer by using screening with low-dose spiral computed tomography (CT) of the chest. MATERIALS AND METHODS: A prospective cohort study was performed with 1,520 individuals aged 50 years or older who had smoked 20 pack-years or more. Participants underwent three annual low-dose CT examinations of the chest and upper abdomen. Characteristics of pulmonary nodules and additional findings were tabulated and analyzed. RESULTS: Two years after baseline CT scanning, 2,832 uncalcified pulmonary nodules were identified in 1,049 participants (69%). Forty cases of lung cancer were diagnosed: 26 at baseline (prevalence) CT examinations and 10 at subsequent annual (incidence) CT examinations. CT alone depicted 36 cases; sputum cytologic examination alone, two. There were two interval cancers. Cell types were as follows: squamous cell tumor, seven; adenocarcinoma or bronchioloalveolar carcinoma, 24; large cell tumor, two; non–small cell tumor, three;...

Senile EBV+ B-cell lymphoproliferative disorders: a clinicopathologic study of 22 patients.

Abstract: Twenty-two Epstein-Barr virus-associated B-cell lymphoproliferative disorders (LPDs) without predisposing immunodeficiencies were evaluated clinically and pathologically. All patients were Japanese and negative for anti-human immunodeficiency virus antibody. They were all more than 60 years old with a median age of 75.5 years. Eighteen (82%) patients showed extranodal involvement. Biopsied specimens contained variable numbers of centroblasts, immunoblasts, and Reed-Sternberg-like giant cells often with necrosis and an angiocentric pattern. The 13 cases showing polymorphous composition and inflammatory background were categorized as polymorphic LPD subtype. The other nine cases contained diffuse proliferative lesions of large lymphoid cells and were categorized as large cell lymphoma subtype. Tumor cells expressed CD20 and/or CD79a, and in situ hybridization showed them to be associated with Epstein-Barr virus. LMP1 was detected in all cases and EBNA2 in seven. Eighteen patients initially received combination chemotherapy, and 12 achieved complete remission. However, six patients were refractory to chemotherapy and four patients with complete remission later relapsed. Eight of the 18 patients who received chemotherapy showed an aggressive disease course within a year after the diagnosis. There was a significant difference in prognosis between the group with polymorphic LPDs and the one with large cell lymphomas (p = 0.003). Although the disease profile of the 22 cases was analogous to that of immunodeficiency-associated B-cell LPDs, none of the patients showed evidence of underlying immunodeficiency-related diseases. These findings suggest that Epstein-Barr virus-associated LPD without immunodeficiency mainly occurs in elderly patients. Further investigations are needed to clarify the pathogenesis of this disease and to determine the optimal treatment strategy.

Identification of Hodgkin and Reed-Sternberg cell-specific genes by gene expression profiling

Abstract: Hodgkin lymphoma (HL) is a malignancy of unknown pathogenesis. The malignant Hodgkin and Reed/Sternberg (HRS) cells derive from germinal center B cells (or rarely, T cells) but have a heterogeneous and largely uncharacterized phenotype. Using microarrays, we compared the gene expression profile of four HL cell lines with profiles of the main B cell subsets and B cell non-HLs to find out whether HRS cells, despite their described heterogeneity, show a distinct gene expression, to study their relationship to other normal and malignant B cells, and to identify genes aberrantly or overexpressed by HRS cells. The HL lines indeed clustered as a distinct entity, irrespective of their B or T cell derivation, and their gene expression was most similar to that of EBV-transformed B cells and cell lines derived from diffuse large cell lymphomas showing features of in vitro‐activated B cells. Twenty-seven genes, most of which were previously unknown to be expressed by HRS cells, showed aberrant expression specifically in these cells, e.g., the transcription factors GATA-3, ABF1, EAR3, and Nrf3. For five genes, expression in primary HRS cells was confirmed. The newly identified HL-specific genes may play important roles in the pathogenesis of HL, potentially represent novel diagnostic markers, and can be considered for therapeutic targeting.

Non-Small-Cell Lung Cancer Molecular Signatures Recapitulate Lung Developmental Pathways

Abstract: Current paradigms hold that lung carcinomas arise from pleuripotent stem cells capable of differentiation into one or several histological types. These paradigms suggest lung tumor cell ontogeny is determined by consequences of gene expression that recapitulate events important in embryonic lung development. Using oligonucleotide microarrays, we acquired gene profiles from 32 microdissected non-small-cell lung tumors. We determined the 100 top-ranked marker genes for adenocarcinoma, squamous cell, large cell, and carcinoid using nearest neighbor analysis. Results were validated by immunostaining for 11 selected proteins using a tissue microarray representing 80 tumors. Gene expression data of lung development were accessed from a publicly available dataset generated with the murine Mu11k genome microarray. Self-organized mapping identified two temporally distinct clusters of murine orthologues. Supervised clustering of lung development data showed large-cell carcinoma gene orthologues were in a cluster expressed in pseudoglandular and canalicular stages whereas adenocarcinoma homologues were predominantly in a cluster expressed later in the terminal sac and alveolar stages of murine lung development. Representative large-cell genes (E2F3, MYBL2, HDAC2, CDK4, PCNA) are expressed in the nucleus and are associated with cell cycle and proliferation. In contrast, adenocarcinoma genes are associated with lung-specific transcription pathways (SFTPB, TTF-1), cell adhesion, and signal transduction. In sum, non-small-cell lung tumors histology gene profiles suggest mechanisms relevant to ontogeny and clinical course. Adenocarcinoma genes are associated with differentiation and glandular formation whereas large-cell genes are associated with proliferation and differentiation arrest. The identification of developmentally regulated pathways active in tumorigenesis provides insights into lung carcinogenesis and suggests early steps may differ according to the eventual tumor morphology.

A training-testing approach to the molecular classification of resected non-small cell lung cancer.

Abstract: Purpose: RNA expression patterns associated with non-small cell lung cancer subclassification have been reported, but there are substantial differences in the key genes and clinical features of these subsets casting doubt on their biological significance. Experimental Design: In this study, we used a training-testing approach to test the reliability of cDNA microarray-based classifications of resected human non-small cell lung cancers (NSCLCs) analyzed by cDNA microarray. Results: Groups of genes were identified that were able to differentiate primary tumors from normal lung and lung metastases, as well as identify known histological subgroups of NSCLCs. Groups of genes were identified to discriminate sample clusters. A blinded confirmatory set of tumors was correctly classified by using these patterns. Some histologically diagnosed large cell tumors were clearly classified by expression profile analysis as being either adenocarcinoma or squamous cell carcinoma, indicating that this group of tumors may not be genetically homogeneous. High α-actinin-4 expression was identified as highly correlated with poor prognosis. Conclusions: These results demonstrate that gene expression profiling can identify molecular classes of resected NSCLCs that correctly classifies a blinded test cohort, and correlates with and supplements standard histological evaluation.

Effects of Carvacrol on a Human Non-Small Cell Lung Cancer (NSCLC) Cell Line, A549.

Abstract: Carvacrol, the predominant monoterpene in many essential oils of Labitae including Origanum, Satureja, Thymbra, Thymus, and Corydothymus has substantial antibacterial, anti fungal, antihelmintic, insecticial, analgesic and antioxidant activities. In this study a human non-small cell lung cancer (NSCLC) cell line, A549 was used. Approximately 75% of lung cancer is non-small cell carcinoma (NSCLC) which comprises several histologic types: squamous cell, adenocarcinoma and large cell carcinoma. It was reported that the proportion of lung tumors diagnosed as adenocarcinoma has increased. For this reason A549 cell line was chosen for this study.

Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new who classification

Abstract: Aim: To study the clinicopathological and immunohistochemical features of 143 cases of primary small and large intestinal non-Hodgkin's lymphoma (NHL) in Japanese patients who presented between 1981 and 2000. Methods and results: The new World Health Organization (WHO) classification was used to classify NHL. The patients included 109 males and 34 females, with an average age of 54.1 years. Tumour sites were as follows: ileocaecal (n = 51, 35.7%), ileum (n = 29, 20.3%), rectum (n = 13, 9.1%), and duodenum (n = 11, 7.7%). Macroscopically, 124 cases (86.7%) were classified as tumorous type, 12 (8.4%) as diffuse infiltration type (erosion, superficial ulceration), five (3.5%) as polyposis type, and only two cases (1.4%) as ulceration type. Immunohistochemically, 122 lesions (85.3%) were of B-cell phenotype and 21 lesions (14.7%) were of T-cell phenotype. According to the WHO classification, of the B-cell lymphomas, 84 cases (68.9%) were large cell, 16 (13.1%) were Burkitt, 10 (8.2%) were marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (MALT), and seven (5.7%) were mantle cell tumours. Among the T-cell lymphomas, 15 (71.4%) were of unspecified type, two (9.5%) were natural killer type, two were anaplastic large-cell lymphomas, one was lymphoblastic, and one was an adult T-cell leukaemia lymphoma. The survival rate for T-cell lymphomas was poorer than for B-cell lymphomas. Among the B-cell lymphomas, mantle cell lymphoma tended to have a poorer prognosis, whereas MALT lymphomas had a better prognosis than other B-cell tumour types. Conclusions: Our retrospective study of patients with primary malignant lymphomas in the small and large intestines has illustrated the clinical features and outcomes of patients with this disease.

Large cell neuroendocrine carcinoma of the uterine cervix: a clinicopathological study of six cases.

Abstract: Six cases of cervical large cell neuroendocrine carcinomas (LCNEC) were found among 972 patients (0.6%) with invasive cervical carcinoma. The patients, who were from 27 to 51 (mean 38) years of age, presented with vaginal bleeding or an abnormal Papanicolaou smear. Five tumors were stage Ib and one was IIa. All patients underwent radical hysterectomy and received adjuvant chemotherapy and pelvic radiotherapy. Four patients died of tumor 6 to 19 months (mean 14 months) postoperatively. On histologic examination, the tumor cells were arranged in an organoid growth pattern and were larger than those of typical small cell carcinoma. Glandular differentiation was present in one case. Mitotic figures ranged from 15 to 45 (mean 29) per 10 high-power fields. Prominent vascular invasion and necrosis was seen in all of the tumors. Each tumor was immunoreactive for chromogranin A and/or synaptophysin. The results of this study confirm the aggressive nature of cervical LCNECs. The recognition of LCNECs is necessary to establish the most effective treatment for these aggressive tumors.

Familial risk of cancer by site and histopathology.

Abstract: Familial risks for histopathology-specific cancers have not been determined. We used the nationwide Swedish Family-Cancer Database on 10.2 million individuals and 1 million tumors to calculate standardized incidence ratios (SIRs) for familial cancers of specific histology and morphology among 0- to 66-year-old offspring. We used histology codes for both offspring and parents, but because of the limited number of cases, the morphology-specific classification could be used only for offspring by all site-specific cancers in parents, resulting in inflated risk estimates. A number of novel findings emerged in the histopathology-specific analysis of familial risks, in addition to some known associations. Overall, specific histology showed an SIR of 2.07 for all cancers compared to an SIR of 2.00 for any histology. However, the small effect was due to breast and prostate cancers, which showed a negligible effect of specific histology. Familial risks of over 4.0 were found for serous papillary cystadenocarcinoma of the ovary, papillary thyroid cancer and low-grade astrocytoma. Familial risks of over 3.0 were found for signet-ring gastric cancer, various forms of ovarian cancer and squamous cell skin cancer. Also noteworthy were familial risks of hepatocellular carcinoma (2.48), pancreatic adenocarcinoma (1.92), large cell carcinoma and adenocarcinoma of the lung (2.29 and 2.18, respectively) and clear cell carcinoma of the kidney (2.73). Many of the findings were novel and could be revealed only by applying codes for specific histopathology. These data call for a closer description of familial aggregations and probing for the underlying genetic mechanisms.

Immunophenotypic analysis of anaplastic large cell lymphoma by flow cytometry.

Abstract: We studied the antigen expression profiles of 19 anaplastic large cell lymphoma (ALCL) cases by multiparameter flow cytometry The neoplastic cells expressed CD45, HLA-DR, and CD30 in all cases At least 1 T cell-associated antigen was expressed in each case (CD2, 12/17 [71%]; CD4, 12/19 [63%]; CD3, 6/19 [32%]; CD7, 6/19 [32%]; CD5, 5/19 [26%]; CD8, 4/19 [21%]) CD25 was expressed in 14 (88%) of 16 cases CD13 was expressed unexpectedly in 8 (47%) of 17 cases One CD13+ ALCL also was positive for CD33 and 2 others for CD15, CD19, CD20, CD22, CD14, and CD36 were not expressed Anaplastic lymphoma kinase protein was detected in about 33% (3/9) of ALCLs examined by flow cytometric immunophenotyping (FCI); expression was validated by immunohistochemical analysis Of 19 ALCL cases, 12 were diagnosed solely based on FCI findings in conjunction with morphologic evaluation of body fluid (1 case), fine-needle aspirate (3 cases), or excisional biopsy specimen (8 cases) The diagnoses of the remaining 7 cases were suggested strongly by FCI and confirmed by immunohistochemical analysis FCI is useful to aid in diagnosis of ALCL, particularly along with fine-needle aspiration evaluation ALCL with aberrant expression of myeloid antigens should not be mistaken for extramedullary myeloid tumor

ALK-positive anaplastic large cell lymphoma with leukemic peripheral blood involvement is a clinicopathologic entity with an unfavorable prognosis. Report of three cases and review of the literature.

Abstract: Leukemic peripheral blood involvement in anaplastic large cell lymphoma (ALCL) is uncommon. We describe 3 children with such manifestations and review the features of 9 pediatric and adult patients previously described in the literature. Leukemic involvement in ALCL may occur at the time of initial diagnosis or develop during the course of disease. It most often is associated with the small cell histologic features and the t(2;5)(p23;q35). Clinical features commonly include significant respiratory distress, diffuse lung infiltrates or pleural effusions, and hepatosplenomegaly. Most cases have an aberrant T-cell immunophenotype with frequent expression of myeloid antigens, most often CD11b or CD13. Ten of the 12 cases reviewed had a poor response to therapy or early relapse. Thus, while anaplastic lymphoma kinase-positive ALCL and young patient age generally are associated with a favorable prognosis, leukemic involvement seems to identify a high-risk malignant neoplasm that requires more aggressive therapy, including hematopoietic stem cell transplantation.

Incidence of potential glycosylation sites in immunoglobulin variable regions distinguishes between subsets of Burkitt's lymphoma and mucosa-associated lymphoid tissue lymphoma

Abstract: Recently, a high incidence of novel N-glycosylation sites introduced by somatic mutation was observed in the immunoglobulin variable region genes of follicular lymphoma. As these are positively selected and are uncommon in normal B cells, they may have a role in tumour growth and behaviour. Sites are not characteristic of chronic lymphocytic leukaemia or myeloma, but are detectable in approximately 50% of diffuse large cell lymphomas. Another feature of the variable region genes of certain lymphomas is ongoing somatic mutation. To determine whether glycosylation is associated with this phenomenon, we analysed variable region gene sequences of Burkitt's lymphoma (BL) and mucosa-associated lymphoid tissue (MALT) lymphoma. Novel sites were common in endemic BL (82%) and in 4/5 patients with Iranian BL. However, sporadic BL had a lower incidence (43%). Patients with MALT lymphoma had a low frequency (9%) of novel sites, comparable to normal B cells. These findings distinguish glycosylation sites from ongoing mutation and may reflect different environmental influences on these tumours.

Mitochondrial DNA mutation correlates with stage progression and prognosis in non-small cell lung cancer.

Abstract: The optimal management of patients with non-small cell lung cancer (NSCLC) depends onthe accuracy of appropriate staging strategies. Thebest approach for clinical staging, especially theevaluation of lymph node metastasis, continuesto confound clinicians. A specific, less-invasivemethod to support preoperative stage evaluation isrequired. Recently, Fliss et al. [2000] reported a highfrequency of mitochondria DNA (mtDNA) mutationin NSCLC. MtDNA is preferentially modified bymany carcinogens and is repaired less efficientlycompared with that of nuclear DNA [Khrapko et al.,1997]. We speculated an association between mtDNAmutation and NSCLC exists and, therefore, se-quenced the mtDNA of tumor cells from NSCLCpatients.This study was reviewed and approved by theKagoshima University Faculty of Medicine Committeeon Human Research.We prospectively investigated 202 NSCLC patients(adenocarcinoma, 106; squamous cell carcinoma,86; bronchoalveolar carcinoma, 4; large cell carcino-ma, 6), including 119 men and 83 women whosemean age was 63.2

Chromosomal instability detected by fluorescence in situ hybridization in surgical specimens of non-small cell lung cancer is associated with poor survival.

Abstract: Purpose: Chromosomal instability (CIN) in non-small cell lung cancer (NSCLC) has yet to be well studied. We examined the relationship between CIN detected by fluorescence in situ hybridization and survival in patients with NSCLC. Experimental Design: Touch preparations from 50 surgical specimens of NSCLC were studied. Tumors included 34 adenocarcinomas, 15 squamous cell carcinomas, and 1 large cell carcinoma. The pathologic stage was IA in 14, IB in 17, IIB in 8, IIIA in 9, and IIIB in 2 cases. Enumeration of chromosomes 3, 10, 11, and 17 was used to determine which tumors carried CIN. The association between CIN and survival was also analyzed. Results: Disomy was most common, but tetrasomy and trisomy of the examined chromosomes were seen frequently. Fourteen tumors (28%) showed heterogeneity of all four chromosomes examined and were judged to be carrying CIN. Both univariate and multivariate analyses revealed that two factors, lymph node metastasis and CIN, were significant poor prognostic factors. Conclusions: CIN in NSCLC detected by fluorescence in situ hybridization is an independent factor predicting a poor prognosis.

Real-Time Reverse Transcription-PCR Detects KS1/4 mRNA in Mediastinal Lymph Nodes from Patients with Non-Small Cell Lung Cancer

Abstract: Non-small cell lung cancer (NSCLC) is the most common cancer-related cause of death for both men and women in the US. Standard therapies for patients with NSCLC include surgery, chemotherapy, and radiation therapy, and the stage of disease dictates choice of therapy. The current staging system for lung cancer uses the American Joint Committee on Cancer TNM system, and its goal is to classify patients into groups based on the extent of disease. This system relies heavily on the pathologic evaluation of the primary tumor (T), regional nodes (N), and distant metastases (M). Patients in whom mediastinal lymph nodes (MLNs) are involved (N2 or N3) are classified with stage III disease (1) and are generally considered inoperable. The recent identification of genes overexpressed in lung cancer (2)(3)(4) combined with advances in real-time reverse transcription-PCR (RT-PCR) provide the opportunity to establish sensitive and specific ways to analyze MLNs. In addition, molecular biology approaches using real-time RT-PCR are well suited to the analysis of lymph node tissue procured through minimally invasive procedures such as endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). This technique enables reliable biopsy of MLNs without the need for general anesthesia or surgery (5). Given the advantages of EUS-FNA, we investigated the possibility that metastatic disease could be reliably detected in MLNs of NSCLC patients by real-time RT-PCR. To define the ability of real-time RT-PCR to detect metastatic NSCLC in MLNs, we procured by EUS-FNA nine MLNs containing metastatic NSCLC (five adenocarcinomas, one large cell carcinoma, one squamous cell carcinoma, and two uncharacterized carcinomas). For negative controls, we collected 30 cervical lymph nodes obtained by surgical resection. Protocols for tissue procurement and patient consent governing all aspects of this study were reviewed and approved by the Medical University of South Carolina Institutional Review Board. For EUS-FNA, a …

Therapy of non-Hodgkin's lymphoma

Abstract: Non-Hodgkin's lymphomas are a heterogeneous group of malignancies of the lymphoid system. The exact etiology for most lymphomas has not been determined, but both viral and bacterial infections have been shown to be important etiologic factors. The WHO classification of hematopoietic and lymphoid tumours classifies lymphomas into B-cell and T-cell neoplasms. B-cell lymphomas account for more than 85% of all lymphomas. The Ann Arbor staging classification has been adopted by the AJCC and UICC as a standard for classifying extent of anatomic disease. The two most common histologic disease entities are follicular lymphomas and diffuse large B-cell lymphomas. The management of follicular lymphomas is used as a paradigm for the management of all indolent lymphomas. Radiation therapy is used for stage I and II disease, while alkylating agent chemotherapy, immunotherapy and radioimmunotherapy are most frequently used in stage III and IV disease that requires treatment. Most patients with follicular lymphoma enjoy prolonged survival, but at present there is no evidence that those with stage III and IV follicular lymphoma can be cured. Diffuse large B-cell lymphomas serve as a paradigm for treating aggressive lymphomas. Stage I and II diffuse large cell lymphomas are generally treated with combined modality therapy with doxorubicin-based chemotherapy followed by involved field radiation therapy, while those with stage III and IV disease are treated with chemotherapy alone. Patients who fail initial management are treated with further chemotherapy. High-dose chemotherapy with stem cell rescue has been shown to be particularly effective as salvage treatment for diffuse large cell lymphomas. The management of a heterogeneous group of primary extranodal lymphomas in general follows the above treatment principles, with additional treatment being required for those with a high risk of CNS failures, or involvement of contralateral paired organs. The management of MALT lymphomas, especially gastric MALT lymphoma, deserves special attention because of the high response rate to Helicobacter pylori eradication therapy.

Identification of a novel homeobox-containing gene, LAGY, which is downregulated in lung cancer.

Abstract: We have isolated a novel gene, lung cancer-associated gene Y (LAGY), by suppression subtractive hybridization. The nucleotide sequence of LAGY predicts a small protein of 73 amino acids containing a putative homeobox domain with a molecular mass of 8.1 kD. Multiple-tissue Northern blot analysis revealed that LAGY is present in human placenta, lung, brain, heart and skeletal muscle. Gene mapping locates LAGY on chromosome 4q11-13.1. The expression of LAGY mRNA was widely lost in 18 lung tumor cell lines comprising all major histological types, as shown by Northern blot analysis and semiquantitative reverse transcription-polymerase chain reaction. In an investigation of 72 primary lung tumors, this gene was significantly downregulated in tumors compared to 9 normal lung tissue samples. There was a significant reduction of LAGY expression in squamous cell carcinoma (SCC; n = 27) with increasing grade and stage. No expression was detectable in two high-grade SCCs or two small cell and large cell lung carcinomas (n = 4 for each). In adenocarcinoma (n = 37), expression was reduced; however, this did not reach statistical significance. Since homeodomain-containing genes are known to transcriptionally regulate key cellular processes and are associated with carcinogenesis, we suggest that LAGY might be linked to lung cancer development and progression.

Prognostic prediction of the immunohistochemical expression of p53 and p16 in resected non-small cell lung cancer

Abstract: Objective: p53 and p16(INK4) are the common and important tumor suppressor genes. Aberrant expression of p53 or p16 protein has been reported in various malignancies including lung cancer. Our aim was to investigate the association of p53 and p16 expression in resected non-small cell lung carcinoma (NSCLC) and evaluated their correlation with clinocopathologic features and survival. Methods: p16 and p53 expression were detected by immunohistochemical analysis of 90 paraffin specimens of resected NSCLC, including 35 squamous cell carcinoma, 47 adenocarcinoma, and eight large cell carcinoma, between stages I and IV. The immunohistochemical study was performed using the labeled streptavidine‐biotin method with anti-p53 and anti-p16 monoclonal antibodies. Results: Fifty-two (57.8%) and 36 (40%) of 90 patients revealed aberrant immunostaining for p53 (p531) and p16 (p161), respectively. While 19 cases (21.1%) showed abnormal immunoreactivity for both p16 and p53. (p531/p161). There was no correlation of p53 or p16 expression with the clinicopathologic features. The Kaplan‐Meier survival analysis demonstrated that patients with p161, p531, late stages, and nodal or distal metastasis had poor survival status (P ¼ 0.006, 0.013, ,0.001, ,0.001 and 0.018, respectively). Further analysis demonstrated that p53 status was a significant prognostic factor in stage I NSCLCs ðP , 0:001Þ, and p16 status in stage I and II NSCLCs (P , 0:001, P ¼ 0:003, respectively). Furthermore, patients whose tumors were both p53 and p16 aberrant expression had worse outcome compared with those whose tumors were both normal expression of p53 and p16 (5-year survival rate: 5 vs. 76%, P , 0:001). In Cox’s regression model, the aberrant expression of p16, p53, advanced stages and combined aberrant expression of p53/p16 survived for a significant shorter period. Conclusions: The results indicated that aberrant expression of p16 and p53 are significant and independent, predictable prognostic factors for resected NSCLC, especially in early stage of NSCLCs. The worst prognosis was seen in patients whose tumors had both aberrant expression of p53 and p16. Further prospective trials may be aimed at confirming and validating these results. q 2002 Elsevier Science B.V. All rights reserved.

CD30-positive T-cell lymphomas co-expressing CD15: an immunohistochemical analysis.

Abstract: The characteristic histologic features and immuno-phenotype are usually diagnostic and allow distinguishing CD30 positive T-cell lymphoma (including anaplastic large cell lymphoma) from classical Hodgkin's lymphoma. The latter differs by expression of CD15 and lack of CD45, pan-T antigens and ALK expression. We report nine cases of large cell hematopoietic neoplasms in which the neoplastic cells co-expressed CD30 and CD15, and had immunophenotypic and morphologic features of T-cell lymphoproliferative process. The average age of the CD15-positive group was 61.9 years; 6 cases occurred in men and 3 in women. The tumors were located in lymph nodes in 8 cases, and in liver in 1 case. Two cases expressed ALK protein. There were no statistically significant differences in phenotypic parameters between the CD15-positive and CD15-negative neoplasms (p>0.05). However, the CD15-positive group appeared to show a minor trend toward less positivity for EMA (44% versus 72%), ALK protein (22% versus 51%), and CD45RO (33.3% versus 83.3%, p=0.07), when compared to the typical CD15-negative neoplasms. In summary, although the co-expression of CD30 and CD15 is typical for classical HL, it may be also present in a subset of peripheral T-cell neoplasms including ALK-positive anaplastic large cell lymphoma. Combined and sensible use of morphology and a broad immunophenotypic panel in cases with limited material and/or those with overlapping histologic patterns will best discriminate between HL and ALCL. It is incumbent upon the pathologist to distinguish between these two clinicopathologic entities, since treatment options and clinical outcomes differ.

Expression, proliferation activity and clinical significance of cathepsin B and cathepsin L in operated lung cancer.

Abstract: Aims To immunohistochemically investigate the expression of cathepsin B and cathepsin L in various lung cancer cell types in association with the patients' prognosis. Materials and methods Histological slides obtained from formalin-fixed, paraffin-embedded tissue of 120 potentially curative resected lung cancer specimens (20 cases of each of the following cell types: squamous cell, adeno, large cell anaplastic, small cell anaplastic, intrapulmonary metastases, mesotheliomas) were quantitatively immunohistochemically analysed with an automated image analysing system and correlated with the patients' prognosis and the tumour proliferation rate measured by the expression of Ki-67. Results The expression of cathepsin B was most frequently present in large cell anaplastic carcinomas and missing in small cell carcinomas. That of cathepsin L was less frequently seen, and mainly expressed in macrophages and adenocarcinoma tumour cells. The structural heterogeneity of cathepsin B expression measured by syntactic structure analysis was greater than that of cathepsin L. The expression of cathepsin B is of prognostic significance in non-small cell lung cancer, and ranges directly after the pN and pT stages in multivariate statistical analysis. Conclusion In concordance with the literature, the expression of cathepsin B in non-small cell lung cancer should be considered as a significant prognostic parameter in contrast to that of cathepsin L, which is not related to the patients' outcome at a statistically significant level.

Cutaneous lymphomas other than mycosis fungoides in Singapore: a clinicopathological analysis using recent classification systems.

Abstract: Summary Background Cutaneous lymphomas other than mycosis fungoides (MF) are a heterogeneous group with wide variations in clinical presentation, biological behaviour and prognosis. New classification systems have been designed or proposed in recent years, with well-defined disease entities and emphasis on the importance of site. Objectives This study aims to analyse a series of non-MF lymphomas in an institution-based dermatological setting in Singapore, based on the European Organization for Research and Treatment of Cancer (EORTC) classification and the World Health Organization (WHO) classification. A secondary objective is to highlight the clinical utility of both classification systems. Patients and methods Forty cases diagnosed over a 12-year period were examined by immunohistochemistry with antibodies targeting CD3, CD4, CD5, CD8, CD20, CD30, CD43, CD45RO, CD56 and CD68 in paraffin-embedded specimens. The immunohistological diagnosis was correlated with the clinical presentation and staging investigations for the final diagnosis and the course of disease recorded. Results Non-MF T-cell lymphomas presenting in the skin comprised 31 cases (78%) and were 3½ times more common than B-cell lymphomas, which comprised nine cases (22%). The common subtypes were lymphomatoid papulosis, CD30+ large cell cutaneous T-cell lymphoma and subcutaneous panniculitis-like T-cell lymphoma. The commonly ascribed B-cell pattern with infiltrates in the mid and deep dermis and perivascular spaces was seen in 60% of T-cell lymphomas. Overall, there were equal numbers of primary cutaneous T-cell lymphomas and those due to concurrent or secondary cutaneous lymphoma. Five of six cases of subcutaneous panniculitis-like T-cell lymphoma had concurrent cutaneous and systemic involvement and their median survival was 7 months. Conclusions The predominance of cutaneous T-cell lymphomas in this case series closely matched that reported from east Asia; cutaneous B-cell lymphomas are much less common than in Europe. The EORTC classification, which is designed only for primary cutaneous lymphomas, should be used in conjunction with the WHO classification because of the high prevalence of cutaneous lymphomas as the secondary site of disease from systemic lymphoma. In addition, subcutaneous panniculitis-like T-cell lymphoma is a primary cutaneous lymphoma where systemic involvement is common at initial presentation. We propose full immunophenotyping and complete clinical evaluation with staging investigations for all patients presenting with cutaneous lymphomas other than MF.