Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oncogenes are important cellular genes that in general promote in the normal growth regulatory pathways. The human c-erb B-2 proto-oncogene (HER-2 or neu) encodes a 185 kDa transmembrane putative growth factor receptor of the tyrosine kinase family. This oncogene has been shown to be over expressed and/or amplified in primary carcinoma of the breast, ovary, pancreas and salivary glands. This study was conducted to evaluate a possible link between amplification of c-erb B-2 oncoprotein and cartilage invasion in laryngeal carcinoma. In addition, data concerning overexpression were compared to other clinicopathological parameters as well as clinical outcomes. In all, 34 patients with squamous cell carcinoma of the larynx were studied prospectively. Total laryngectomy specimens were sliced in horizontal sections at 4- to 5-mm intervals. Specimens were preserved in 10% formalin, and histopathological examinations were carried out after embedding tissues in paraffin sections and then staining them with hematoxylin and eosin. Detection of c-erb B-2 oncoprotein overexpression was carried out with a polyclonal antibody and an avidin-biotin kit. The level of c-erb B-2 overexpression was determined using the Quantimet 520 Leica image analyzing system. However, no significant correlation was found between cartilage invasion and clinicopathological parameters and prognosis. Overexpression of c-erb B-2 attained no significant correlation with clinicopathological parameters. In contrast, the correlation of c-erb B-2 overexpression and cartilage invasion was statistically significant (P = 0.034). In general, overexpression of c-erb B-2 oncoprotein was related to the more aggressive tumors with high capability of invading laryngeal cartilages. Patients with +ve c-erb B-2 oncogene had a poor prognosis but this was not statistically significant when compared to the clinical outcomes of patients with the -ve c-erb B-2 oncogene.
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PMID:Expression of c-erb B-2 oncoprotein in cancer of the larynx in relation to invasion of the cartilagenous framework and prognosis. 1006 94

Serious and endometrioid carcinomas differ dramatically in their clinical behavior; however, the specific significance of villoglandular (papillary) differentiation in endometrioid carcinoma has been studied rarely. We compared the clinicopathologic features and genetic alterations in 28 villoglandular endometrioid carcinomas compared with 60 nonvilloglandular endometrioid carcinomas and 60 healthy women. The study revealed a slight increase in the frequency of early-stage disease in villoglandular tumors compared with nonvilloglandular tumors. No differences were observed in the age at onset or cellular grade. The oncogene and susceptibility gene analyses revealed a positive association of K-ras oncogene mutation and germline variants of the cytochrome P-450 1A1 (CYP1A1) gene and an inverse association of the p53PIN3 variant with villoglandular carcinomas, whereas no differences were observed in the c-erbB2/neu oncogene amplification or the methylenetetrahydrofolate reductase germline variant. Finally, a positive association was found between CYP1A1 and methylenetetrahydrofolate reductase variants and the presence of papillary differentiation in the myometrial component. The results suggest that the villoglandular differentiation pattern arises without aggressive clinicopathologic features in a genetic background of transforming and carcinogen-metabolism genes, characteristic of estrogen-related endometrial tumors (type 1) not exhibiting an unfavorable prognosis.
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PMID:Clinicopathologic features and genetic alterations in endometrioid carcinoma of the uterus with villoglandular differentiation. 1007 8

The involvement of human papillomavirus (HPV) in the development of carcinomas of the uterine cervix has been firmly established. However, other genetic alterations also play an important role in the pathogenesis of cervical cancer. Therefore, we have investigated the role of several (onco)genes in cervical carcinoma. In tumors from 136 patients with stage I and II cancer of the uterine cervix, the expression of epidermal growth factor receptor (EGFR), c-erbB-2/neu, p53, and murine double minute 2 (MDM-2) was studied using immunohistochemistry. In 32 cases, amplification of EGFR, c-erbB-2/neu, MDM-2, and c-myc was studied by Southern blot hybridization. The expression levels of these proteins were correlated with HPV positivity, International Federation of Gynecologists and Obstetricians stage, lymph node metastases, tumor diameter, vessel invasion, and disease-free and overall survival. Moderate/strong expression of EGFR was observed in 54% of tumors. c-erbB-2/neu was focally positive in 12 cases. p53 showed moderate/strong expression in 32% of the tumors. Thirteen % of tumors showed a moderate/strong expression of MDM-2, and this expression was correlated to p53 expression (P<0.001). Only moderate/strong expression of EGFR was associated with reduced disease-free (P = 0.002) and overall survival (P = 0.003). In multivariate analysis, the association of EGFR overexpression with poor prognosis was independent from lymph node status. Gene amplification was found for EGFR (four cases), c-erbB-2/ neu (two cases), and c-myc (six cases). In two tumors, rearrangement of c-myc was found, probably due to the integration of HPV. In conclusion, overexpression of the EGFR is an independent predictor for prognosis in earlier stages (stage I and II) of cervical cancer. p53 and MDM-2 expression are correlated to each other and may play a role in the interaction with HPV. The importance of c-erbB-2/neu and c-myc amplification is relatively small in stage I and II cervical cancer.
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PMID:Oncogene alterations in carcinomas of the uterine cervix: overexpression of the epidermal growth factor receptor is associated with poor prognosis. 1010 Jul 9

TAB-250 and BACH-250 are murine and human chimeric antibodies directed at the extracellular domain of the gp185c-erb-2 (HER2/neu) growth factor receptor overexpressed in a variety of tumor types, including ovarian and breast carcinoma. The ribosome-inhibiting plant toxin gelonin (rGel) was chemically coupled to both antibodies, and the resulting immunotoxins were purified and tested in vitro against human tumor cells expressing various levels of HER-2/neu and in vivo against human tumor xenograft models. The binding of both BACH-250 and BACH-250/rGel conjugate to target cells was essentially equivalent. Against SKOV-3 cells, the IC50 of BACH-250/rGel was 97 pM (17 ng/ml), whereas BACH-250 and rGel alone showed no cytotoxic effects. There was a clear correlation between expression levels of HER-2/neu and cytoimmunotoxin. Tissue distribution studies showed that the antibody and immunotoxin both concentrate 2-10-fold higher in tumors than in normal tissues, with optimal tumor uptake occurring 48-96 h after administration. Plasma clearance curves for BACH-250 and BACH-250/rGel showed terminal-phase half-lives of 26 and 72 h, respectively. In athymic mice bearing s.c. or i.p. SKOV-3 tumors, immunotoxin treatment slowed tumor growth by 99 and 94 % at days 35 and 49 after implantation, respectively, and lengthened the median survival by 40% (from 30 to 50 days) in mice bearing lethal i.p. tumors. We conclude that clinical development of BACH-250/rGel may be warranted in patients with HER2/neu-expressing malignancies.
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PMID:Recombinant immunotoxins directed against the c-erb-2/HER2/neu oncogene product: in vitro cytotoxicity, pharmacokinetics, and in vivo efficacy studies in xenograft models. 1021 23

Tumour progression is strongly associated with a series of specific genetic changes in protooncogenes and tumour suppressor genes. One of the potential factors involved in tumorogenesis of squamous cell carcinomas is protooncogene c-erbB-2 (also known as neu or HER2). The authors analysed the expression of c-erbB-2 oncoprotein in 154 cases of laryngeal squamous cell carcinomas and its relationship to the clinical outcome of the patients. The difference in c-erbB-2 oncoprotein expression between the control group and cancer patients was on the statistical borderline (p = 0.0470). There was no significant correlation between c-erbB-2 expression and sex and age of the patients. T stage, lymph node status, site and histopathological grading of the tumour and clinical outcome of the patients. Univariate analysis revealed no correlation between c-erbB-2 expression and survival rates. We conclude that immunohistological examination of c-erbB-2 on paraffin section is not a valuable prognostic factor in laryngeal carcinoma.
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PMID:C-erbB-2 immunostaining in laryngeal cancer. 1038 Jul 48

The detection of specific genetic alterations in breast cancer is useful for diagnosing, predicting prognosis and planning preoperative treatment. c-erbB2/neu overexpression is usually detected by immunocytochemistry (ICC), although this technique is neither completely reproducible nor highly reliable, owing to specimen and methodologic variability and antibody sensitivity. Here, we combine two well-established techniques, fine-needle aspiration (FNA) and fluorescence in situ hybridization (FISH), to detect c-erbB2/neu amplification in patients candidate to primary chemotherapy and, in part, previously analysed for c-erbB2/neu overexpression. Sixty smears from FNA were used to simultaneously detect c-erbB2/neu and chromosome 17 centromere. FISH was successful in 58 cases and detected 24 amplified cases, three of which were negative by immunophenotyping, 28 negative cases, with evidence of two normal c-erbB2/neu/signals, two cases with deletion of c-erbB2/neu, and four cases with polysomy, thus providing more reliable and informative results than ICC. This study underlines the advantages offered by the FNA and FISH combination which are two rapid, reliable, simple and informative techniques, to analyse one of the most important genetic markers for predicting prognosis and chemotherapy planning for breast carcinoma in particular in the light of the recently proposed trials of primary chemotherapy.
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PMID:c-erbB2/neu gene and chromosome 17 analysis in breast cancer by FISH on archival cytological fine-needle aspirates. 1040 62

Biological markers associated with in situ carcinoma and atypical intraductal hyperplasia in the breast are examined to help in identifying a subgroup of premalignant lesions whose natural history may be influenced by epigenetic factors. The biomarkers may be used as indices in clinical trials aiming to assess the effect of weight reduction, dietary intervention or hormone replacement therapy on the risk of progression to invasive breast cancer. In the current state of knowledge, the expression of oestrogen receptors, p53, bcl-2 and HER-2 neu oncogenes and the Ki-67 index of proliferative activity, are the most useful biomarkers for this purpose. In situ carcinoma of the breast manifests a variety of morphological phenotypes with specific biological characteristics. There is evidence that only a proportion of premalignant lesions are committed to progression to invasive cancer while other lesions undergo spontaneous regression at the time of the menopause. Cross-cultural studies suggest that it is the late-stage epigenetic promoting factors which are responsible for the high incidence of postmenopausal breast cancer in Western women. Obesity in middle life and the Western diet favour the development of hyperinsulinaemic insulin resistance, and the metabolic-endocrine effects of its concomitants may promote mammary carcinogenesis around the time of the menopause and increase the incidence of invasive cancer after the menopause. Because biomarker changes in premalignant lesions are nearer in time to these promoting influences, they could provide intermediate endpoints for testing the hypothesis.
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PMID:Premalignant breast lesions: role for biological markers in predicting progression to cancer. 1050 26

The step of intravasation or lymphovascular invasion can be a rate-limiting step in the metastatic process. Inflammatory breast carcinoma manifests an exaggerated degree of lymphovascular invasion in situ; hence, a study of its molecular basis might shed light on the general mechanism of lymphovascular invasion exhibited by all metastasizing cancers. To this end, we have established the first human transplantable inflammatory breast carcinoma xenograft (MARY-X) in scid/nude mice. Whereas all other human xenografts grew as isolated s.c. nodules, MARY-X grew exclusively within murine lymphatics and blood vessels, and these latter elements and their supporting stroma comprised, by murine Cot-1 DNA analysis, 30% of the tumor. MARY-X, like its human counterpart, exhibited striking erythema of the overlying skin. MARY-X was estrogen receptor, progesterone receptor, Her-2/neu negative and p53, epidermal growth factor receptor positive. The primary tumor of origin of MARY-X exhibited identical markers, except that about 50% of its cells exhibited Her-2/neu amplification. Comparative studies of MARY-X with noninflammatory xenografts indicated 10-20-fold overexpression of E-cadherin and MUC1, findings that were reflected in actual cases of human inflammatory breast cancer. MARY-X should allow us to further dissect out both the upstream regulatory machinery and the downstream effector molecules responsible for the inflammatory carcinoma phenotype.
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PMID:A novel human xenograft model of inflammatory breast cancer. 1053 77

Benign proliferative nipple duct lesions (PNDLs) pose a diagnostic problem for clinicians and pathologists. Clinically, they may be associated with skin changes typically present in Paget's disease of the nipple. The identification of numerous scattered cells in the epidermis that are immunoreactive for low-molecular-weight cytokeratin may lead to further confusion with Paget's disease. We studied the nipple epidermis in nine cases of PNDL and compared them with 26 histologically normal nipples from mastectomy specimens. CAM 5.2 and anticytokeratin 7 (CK7) immunoreactive cells were identified in the epidermis of seven of nine nipples associated with PNDL. The cytokeratin-positive cells appeared cytologically benign and were dispersed singly (scattered in seven of seven cases and frequent in four of seven cases) or formed small aggregates with occasional tubular structures (three of seven cases) in the basal and middle layers of the epidermis. In two of seven cases, these epidermal immunoreactive cells showed continuity with the underlying PNDL, suggesting the spread or continuation of lesional cells to the epidermis. Dispersed single immunoreactive cells were identified in small numbers (scattered) in the basal layer of the epidermis in 12 of 26 normal nipples and more frequently in 1 of 12 cases. In all cases, the intraepidermal cells were negative for carcinoembryonic antigen (CEA) and Her-2/neu. We conclude that intraepidermal CAM 5.2 and anti-CK7 immunoreactive cells, which are normally present in the nipple epidermis, may proliferate and form aggregates when there is an underlying PNDL. The presence of these cells does not imply Paget's disease when the intraepidermal cells have a bland cytologic appearance, fail to overexpress Her-2/neu, and there is no carcinoma within the PNDL or elsewhere in the breast.
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PMID:Benign proliferative nipple duct lesions frequently contain CAM 5.2 and anti-cytokeratin 7 immunoreactive cells in the overlying epidermis. 1055 3

Her-2/neu (H2N) status in breast carcinoma has been considered a prognostic factor that may have therapeutic implications; however, the correlation between H2N overexpression and gene amplification has not been completely defined. A consecutive series of ductal carcinomas (34 invasive and 7 in situ) were analyzed by fluorescent in situ hybridization for H2N gene and chromosome 17 copy number using touch preps of intact cells and by immunohistochemistry, using three different commercial antibodies to H2N protein (Zymed, clone 31G7; Ventana, clone CB11; and Dako, polyclonal) in corresponding formalin-fixed, paraffin-embedded tissue sections. Gene amplification was classified as unequivocal if more than five signals were present in more than 80% of the counted nuclei and absent if more than 80% of the nuclei counted contained two or fewer gene copies. Cases that did not fulfill the above criteria were considered equivocal for amplification. Immunostaining was classified as follows: 0 = no staining; 1+ = faint, incomplete membranous pattern; 2+ = moderate, complete membranous pattern; 3+ = strong membranous pattern. Of the 34 invasive tumors, 10 (29%) had unequivocal gene amplification. Furthermore, all had more than 10 copies of the gene in more than 60% of the counted nuclei. An additional nine cases (26%) had equivocal amplification, which was usually the result of chromosome 17 aneuploidy (seven of nine) or heterogeneity. With the Zymed and Dako antibodies, all tumors with 3+ staining had unequivocal gene amplification and all cases with 2+, 1+, or 0 staining were negative or equivocal for gene amplification. With the Ventana antibody, all cases with 3+ staining had unequivocal gene amplification, but two cases with unequivocal amplification by fluorescent in situ hybridization exhibited 1+ staining. Moderate (2+) H2N staining was observed in one case, three cases, and five cases with the Ventana, Dako, and Zymed reagents, respectively, and did not correlate with H2N gene copy number. Discordance between H2N and chromosome 17 copy number was not a useful means of defining amplification. Two cases of ductal carcinoma in situ with the Zymed antibody and two with the Dako antibody showed 3+ staining despite lack of unequivocal gene amplification. We conclude that (1) strong H2N immunostaining is highly associated with gene amplification, although there is minor variation in sensitivity between different antibodies; (2) a subset of breast carcinomas (3 to 15%) demonstrate moderate H2N staining without evidence of amplification, and it is unclear whether they represent highly sensitive staining or are a subset of cases that show overexpression without amplification; (3) gene amplification, as detected by fluorescent in situ hybridization, is associated with at least 10 gene copies per nucleus, and lower gene copy duplication (3 to 4/nucleus) is frequent, usually the result of chromosome 17 polysomy, and not associated with high-level overexpression; (5) overexpression of H2N without amplification may be more frequent in ductal carcinoma in situ, implying a different role in the biology of preinvasive versus invasive neoplasm.
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PMID:Determination of Her-2/Neu status in breast carcinoma: comparative analysis of immunohistochemistry and fluorescent in situ hybridization. 1126 38


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