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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of ras oncogene product p21 and epidermal growth factor (EGF) receptor was studied immunohistochemically in tissues obtained from 52 patients with squamous cell carcinoma of the uterine cervix. We examined the relationship between p21 and EGF receptor expression and lymph node metastasis in cervical cancer. The data demonstrate that the patients with positive staining for ras p21 in cervical carcinomas have a higher incidence of lymph node metastasis than the patients with negative staining for p21 (P = 0.027). Although the levels of p21 expression in the metastatic sites were reduced compared to those in the primary sites, tumor cells in metastatic lymph nodes also expressed p21. No relationship was found between EGF receptor expression and lymph node metastasis. These results suggest that expression of ras oncogene product may be associated with the biological aggressiveness of cervical carcinomas.
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PMID:Expression of ras oncogene product and EGF receptor in cervical squamous cell carcinomas and its relationship to lymph node involvement. 170 25

To evaluate epidermal growth factor (EGF) receptor expression in the neoplastic process of squamous cell epithelium of the uterine cervix, normal, premalignant, and malignant cervical tissues were examined for the presence of EGF receptor by the avidin-biotin immunoperoxidase techniques with a monoclonal antibody to EGF receptor. Although normal cervical epithelium did not show appreciable staining for EGF receptor, predominant staining for the receptor was observed in most dysplastic epithelia and carcinomas in situ. In invasive squamous carcinoma, there was a great difference in the immunohistochemically detected levels of EGF receptor among the histologic cell types. Large cell nonkeratinizing carcinoma and its keratinizing counterpart contained high levels of EGF receptor; small cell nonkeratinizing carcinoma lacked immunostainable EGF receptor. These results suggest that the elevated expression of EGF receptor may be involved in the initial stage of tumorigenesis of cervical squamous epithelium and that EGF receptor expression may be related to the differentiation or dedifferentiation of cervical squamous carcinoma cells.
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PMID:Immunohistochemical demonstration of elevated expression of epidermal growth factor receptor in the neoplastic changes of cervical squamous epithelium. 173 18

The expression of epidermal growth factor receptor (EGF-R), c-erbB-2 proto-oncogene, and estrogen receptor (ER) was studied immunohistochemically in a series of 97 human papillomavirus (HPV) lesions of the uterine cervix, with special emphasis on their association with the HPV type, grade of intraepithelial neoplasia (CIN), and the natural history of the disease. EGF-R expression was found in 95 of 97 (98%) specimens, mainly in basal and parabasal cells. Diffuse nuclear and cytoplasmic staining was detected in 36 of 97 (37%) samples, of which 29 were HPV positive. This staining pattern was most prominent in HPV 18-positive and in CIN lesions. Weak or moderate c-erbB-2 expression was found in 26 of 97 (27%) specimens. Estrogen receptor expression was observed in 28 of 77 (36%) samples, epithelial staining was seen in 11 of 77 (14%), and stromal staining occurred in 24 of 77 (31%) specimens. No clear-cut associations were established between the EGF-R, c-erbB-2, or ER expression and HPV type, nor in CIN or the clinical course of HPV infections. This failure for EGF-R, c-erbB-2, and ER to be associated with the specific HPV types, grade of CIN, or the clinical course of cervical HPV lesions suggests that the assessment of these factors is of limited value in explaining the development of HPV-associated CIN and in predicting the prognosis of this disease.
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PMID:Epidermal growth factor receptor, c-erbB-2 proto-oncogene and estrogen receptor expression in human papillomavirus lesions of the uterine cervix. 792 56

The c-erbB-2 proto-oncogene (HER-2/neu) codes for a transmembrane, tyrosine kinase, 185 kD oncoprotein (p185erbB2), which is related to the epidermal growth factor receptor. p185erbB2 overexpression occurs in carcinomas at many sites, including the uterine cervix, and predicts poor clinical outcome. The authors hypothesize that p185erbB2 immunohistochemistry will provide additional information in the evaluation of uterine cervix carcinomas with glandular differentiation (CCGD), a difficult and more frequent clinical problem. Paraffin sections from 82 CCGDs including 41 pure adenocarcinomas and 41 adenosquamous carcinomas (7 glassy cell predominant and 34 exhibiting a gland forming component) are immunostained with anti-p185erbB2 (CB11 monoclonal, Novacastra Laboratories, Newcastle upon Tyne, UK). Seventy-seven percent of CCGDs exhibit p185erbB2 immunoreactivity with distinct plasma membrane localization (M) in 50%, the remaining 27% show cytoplasmic staining only. Adjacent benign tissue is negative. The p185erbB2 staining intensity and distribution is as follows: 54.9% strong diffuse (SD, > or = 50% cells positive) with 40.2% M, 17.1% strong focal (SF, < 50% cells positive) with 9.8% M, and 4.9% weak with no M. Immunoreactivity occurs in both squamous and glandular areas of adenosquamous carcinomas. Endometrioid histology is associated with absence of p185erbB2 (P < .01); all other histopathologic features show no association. Follow-up information is available in 77 patients: 37 exhibit recurrent disease (8 pelvic, 15 distant and 14 both) at 1 to 144 months (mean 34, median 16) and 40 were disease free at 12 to 216 months (mean 75, median 64). Strong p185erbB2 immunoreactivity predicts recurrence at 24 months (P < .05) but not overall recurrence at longer follow-up periods. Recurrent disease is associated with nuclear grade (P < .00001); high clinical stage (P < .001); vascular space invasion (P < .001); large size on clinical exam or pathologic evaluation (P < .005); and pelvic lymph node involvement (P < .05). Considering only patients in good prognosis groups, p185erbB2 immunoreactivity does not predict recurrence. Strong p185erbB2 immunoreactivity is associated with stage 3,4 disease (P < .01). p185erbB2 expression is associated with CCGD carcinogenesis but occurs late in the disease, in patients who present at late stage, hindering its prognostic predictive value. p185erbB2 immunolocalization may have a diagnostic role in confirming CCGD in histologically challenging cases, predicting high stage at initial biopsy, and defining therapeutic strategies.
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PMID:c-erbB-2 oncoprotein overexpression in uterine cervix carcinoma with glandular differentiation. A frequent event but not an independent prognostic marker because it occurs late in the disease. 885 48

The authors studied the prognostic value of EGFR and c-erbB-2 overexpression in adenocarcinoma of the uterine cervix. The aim of this research was to find a new pathway to prognosis for more adequate therapy.
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PMID:Prognostic significance of epidermal growth factor receptor (EGFR) and c-erbB-2 protein overexpression in adenocarcinoma of the uterine cervix. 885 1

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

Twelve well-differentiated villoglandular adenocarcinomas (WDVAs) of the uterine cervix were retrospectively analyzed for the presence and specific genotype of human papillomavirus (HPV), tumor suppressor loss (p53, MCC, APC, BRCA1), cancer gene mutation (K-ras-2, exons 1 and 2, p53 exons 5 to 8), and oncogene amplification (c-erbB-2/HER-2/neu, int-2). Tissue for genetic evaluation was obtained by microdissection, using 4-micron-thick histology sections of archival, formalin-fixed, paraffin-embedded specimens. Genotyping involved nucleic acid amplification and DNA sequencing with gene-specific oligonucleotides and L1 region consensus primers for common strains of HPV. Point mutation and HPV strain determination were accomplished by DNA sequence analysis. Tumor suppressor gene loss and oncogene amplification were performed by allelic imbalance analysis in informative subjects based on DNA sequence and microsatellite-length polymorphisms. HPV was present in all tumors and consisted of type 16 (n = 5, 42%) and type 18 (n = 7, 58%) strains, which have been closely associated with cervical neoplasia. K-ras-2 and p53 genes did not manifest point mutational damage. There was no evidence of oncogene amplification or tumor suppressor gene loss. The presence of HPV in all 12 tumors supports the role of HPV infection in the molecular pathogenesis of this uncommon neoplasm. The absence of associated oncogene or tumor suppressor gene damage is consistent with indolent biological behavior and the favorable prognosis of this unusual tumor.
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PMID:Well-differentiated villoglandular adenocarcinoma of the uterine cervix: oncogene/tumor suppressor gene alterations and human papillomavirus genotyping. 1078 6

Ancillary techniques such as immunohistochemistry (IHC) enable the surgical pathologist to extract additional information from fixed, deparaffinized tissue specimens and to provide data critical to optimal clinical management of the patient. In this review of applications of IHC to the analysis of gynecologic malignancies, the usefulness of immunohistochemical analysis of neoplasms of the cervix, endometrium, and ovary is summarized. In the uterine cervix, dysplasia is associated with qualitative and quantitative alterations in the expression of the Ki-67 antigen expression, as well as an ability to detect human papillomavirus. Endometrial endometrioid adenocarcinomas display a highly characteristic immunophenotype, with coexpression of cytokeratin and vimentin and demonstration of foci of high molecular weight cytokeratin expression; in addition, IHC analysis of estrogen and progesterone receptor and p53 expression can provide important prognostic information about this tumor. Stromal tumors of the endometrium may display a partial smooth muscle immunophenotype, but novel markers such as CD10 provide new tools for the identification of these tumors. The immunophenotypes of the normal ovarian surface epithelium (OSE) and corresponding tumors display significant overlap with, but important distinctions from, mesothelium, and important new markers such as the Wilms tumor gene product can prove useful in the identification of carcinomas of the OSE. Important prognostic markers for carcinomas of the OSE include the HER-2/neu gene product and p53, alterations of which can both be assessed by IHC techniques. Finally, the recent availability of markers of ovarian stroma, including Melan-A and inhibin-alpha, has provided a means for the positive identification of ovarian stromal tumors, which can manifest protean histological appearances.
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PMID:Immunohistochemical analysis of gynecologic tumors. 1119 73

Tissues from 50 cases of squamous cell carcinoma of the uterine cervix were analysed for immunohistochemical expression of c-erbB-2 oncoprotein and the patients were followed-up for 2 years. Immunopositivity of c-erbB-2 was studied with reference to clinical stage, histopathological differentiation and response to the cancer therapy. Expression of c-erbB-2 protein was found to be higher (37.5%) in cases with stage II disease, whereas more expressions were noticed in poorly differentiated squamous cell carcinoma (33.3%). Among cases who showed complete response to the treatment, 20.8% were positive for c-erbB-2 oncoprotein. On the contrary, 36.8% of prognostically unfavourable cases revealed positivity for c-erbB-2 immunostaining. However, the difference between c-erbB-2 expressions of these two said groups of patients, which were divided in accordance with the response to treatment, did not attain to statistical significance. Study on c-erbB-2 among larger number of patients with cervical carcinoma may prove to be an important factor in response to cancer therapy.
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PMID:Oncoprotein c-erbB-2 in squamous cell carcinoma of the uterine cervix and evaluation of its significance in response of disease to treatment. 1148 Feb 25

Over-expression of epidermal growth factor receptor (EGFR) and c-erbB-2, in uterine cervical carcinomas, is associated with a worsened prognosis. A third member of this proto-oncogene family, c-erbB-3, has now been identified and its over-expression has been described in a variety of carcinomas. In this immunohistochemical study we have shown that c-erbB-3 is widely expressed in cervical carcinomas, but we have found no association between its over-expression and lymph node status or clinical outcome. In a similar study examining the expression of EGFR and c-erbB-2 it was possible to demonstrate an association between over-expression and a worse prognosis. We conclude, therefore, that it is unlikely that demonstration of c-erbB-3 over-expression will be of any value as a prognostic indicator in carcinoma of the uterine cervix.
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PMID:c-erbB-3 proto-oncogene expression in uterine cervical carcinoma. 1157 90


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