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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Few molecular genetic alterations have been identified in endometrial cancers that are associated with poor clinical outcome. Overexpression of HER-2/neu, transforming growth factor alpha, and p53 proteins have all been associated with poor prognosis in women with endometrial cancer. In this study, the level of HER-2/neu gene amplification and expression was characterized in 92 endometrial cancers. Fluorescence in situ hybridization (FISH) was used to characterize HER-2/neu gene copy number, and immunohistochemistry was used to characterize expression. Forty-seven of the 90 (52%) endometrial cancers were characterized as showing moderate or high immunostaining. HER-2/neu gene amplification was detected in 17 of 81 (21%) cases. Immunohistochemical staining and FISH results were both available for 80 cases. Fourteen of these cases showed both moderate or high immunostaining and gene amplification. Clinical follow-up information was available for 76 women in this study. Women whose endometrial cancer exhibited HER-2/neu gene amplification by FISH had a shorter overall survival than women whose endometrial cancer lacked amplification (P = 0.018). Likewise, tumors with moderate or high HER-2/neu immunostaining were associated with a lower cumulative overall survival than tumors with low immunostaining by log rank analysis (P < 0.0001). Multivariate analysis of survival rates revealed HER-2/neu overexpression to be an independent predictor of overall survival (P = 0.0163). Among those patients with HER-2/neu overexpression, adjuvant chemotherapy or radiation therapy was associated with an improved overall survival (P = 0.039). However, among those women whose tumor lacked overexpression, overall survival was not improved by adjuvant treatment.
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PMID:Amplification and overexpression of HER-2/neu (c-erbB2) in endometrial cancers: correlation with overall survival. 758 56

We studied the expressions of aberrant epidermal growth factor receptor (EGFR) gene or erbB-2, which is highly homologous to EGFR gene, and erbA or estrogen receptor (ER) gene, which is highly homologous to erbA, as a preliminary study, to know which oncogene expressions are associated with the development of endometrial cancers. ErbB-2 mRNA lacked only extracellular domain (EX), suggesting the lack of downregulation of erbB-2 expression by a ligand, which led to regulated tyrosine kinase activity. Mutated DNA binding domain of ER mRNA were found in 3 of the 13 cases, suggesting the promotion disorder of estrogen-inducible proteins in these 3 endometrial cancers. The behavior of aberrant erbB-2 and ER gene co-expressions is considered of similar to that of erbA and erbB co-expressions in the chicken introduced by the avian erythroblastosis virus, which leads to the development of erythroblastosis in the chick, and seems to be associated with the development of endometrial cancer.
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PMID:Preliminary study of oncogene expressions in endometrial cancers. Aberrant estrogen receptor gene and erbB-2 expressions. 774 15

Estra-1,3,5 (10)-triene-3,17-diol (17 beta)-, 3-[bis(2-chloroethyl) carbamate] (Estramustine EM) was tested for its anticancer effect on human endometrial cancer cell lines: Ishikawa and its estrogen (E) independent sub-clone EIIL (Estrogen Independent Ishikawa Line). The results showed: (1) EM inhibited growth of both cell lines in a dose dependent manner giving ID50 for Ishikawa as 12 microM and for EIIL as 65 microM. (2) The addition of EM to the culture medium caused cell detachment and death associated with a breakdown of DNA to approximately 90 base pair fragments. (3) Reverse transcription-polymerase chain reaction to examine expressions of c-erbB-2, nidogen and fas showed that EM completely abolished fas expression and resulted in a 40% decrease in nidogen expression in Ishikawa but not in EIIL. No change was seen in c-erbB-2 expression. The present data indicate that the E component of EM does not stimulate the growth of Ishikawa or EIIL. Since the growth of both cell lines was inhibited but apparently in an E receptor (ER) dependent manner, EM may be of value in an adjuvant therapy for endometrial cancer, especially an ER positive one.
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PMID:[Estramustine phosphate, estrogen conjugated with nitrogen mustard inhibits the growth of endometrial cancer cells in vitro]. 777 15

Expression of four biologic markers was studied in 69 cases of endometrial cancer to identify their association with cell type, decreased survival, and increased tumor metastasis. Cell types included endometrioid (n = 45), serous papillary (n = 16), and clear cell (n = 8). Immunohistochemical stains were employed to detect the presence of epidermal growth factor receptor (EGFR), HER-2/neu, p53, and proliferating cell nuclear antigen (PCNA). Analysis revealed that EGFR was expressed in 49%, HER-2/neu in 59%, p53 in 9%, and PCNA in 16% of tumor specimens. HER-2/neu overexpression was significantly associated with depth of myometrial invasion. p53 and PCNA immunoreactivity significantly correlated with nonendometrioid histology, although PCNA was less specific in labeling these less favorable cell types. EGFR immunoreactivity also significantly correlated with nonendometrioid cell types and tumor metastases at time of diagnosis. Seventy-seven percent of patients with metastatic disease were EGFR-positive versus 36% positivity in patients with no evidence of metastases (P < 0.002). For patients with endometrioid adenocarcinoma, evidence of EGFR overexpression decreased survival from 89 to 69% (P < 0.04). In the serous papillary and clear cell category, EGFR positivity decreased survival from 86 to 27% (P < 0.03). EGFR strongly correlates with tumor metastasis and patient survival in endometrial cancer. Altered expression of this oncoprotein may serve as a guide to prognosis and treatment in these patients.
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PMID:Expression of EGFR, HER-2/neu, P53, and PCNA in endometrioid, serous papillary, and clear cell endometrial adenocarcinomas. 790 88

Abnormal expression of p53, transforming growth factor alpha (TGF alpha), epidermal growth factor receptor (EGFR), and c-erbB-2 occurs in a variety of cancers and in some cases is associated with poor prognosis. Immunoperoxidase staining using these markers in formalin-fixed, paraffin-embedded endometrial carcinoma tissue was performed to determine whether immunoreactivity correlates with survival and known prognostic variables. Cases included 84 endometrioid adenocarcinomas, five adenoacanthomas, 12 adenosquamous carcinomas, 11 serous carcinomas, 15 clear cell carcinomas, and one carcinosarcoma for a total of 128 cases. Frequencies of immunoreactivity were as follows: p53, 37 of 128 (29%); TGF alpha, strong (2+) 23 of 128 (18%) and intermediate (1+) 26 of 128 (20%); EGFR, strong (3+) 21 of 128 (16%) and intermediate (2+ or 1+) 83 of 128 (65%); and c-erbB-2, strong (2+) four of 128 (2%) and intermediate (1+) three of 128 (1%). p53 and TGF alpha staining showed statistically significant correlations with decreased length of survival (P < .0017 and P < .0013, respectively, generalized Savage [Mantel Cox]). p53 immunoreactivity correlated with tumor types, grade, and stage. Transforming growth factor alpha staining correlated with increased depth of invasion and presence of vascular invasion. Epidermal growth factor receptor staining did not correlate with length of survival or known prognostic variables. c-erbB-2 staining correlated with tumor type. In the multivariate analysis p53 and TGF alpha staining were not independent predictors of survival when other variables were taken into account, including grade, stage, tumor type, presence of vascular invasion, and depth of invasion. Grade and stage were the only independent predictors of survival when used in combination in a Cox proportional hazards model.
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PMID:Expression of p53, transforming growth factor alpha, epidermal growth factor receptor, and c-erbB-2 in endometrial carcinoma and correlation with survival and known predictors of survival. 792 13

Both epidermal growth factor receptor (EGFR) and HER-2/neu (neu) have been found to be of prognostic importance in epithelial ovarian and endometrial carcinoma, but alterations in proto-oncogene expression of normal tissues of patients with gynecologic malignancies are unknown. Patients (118) undergoing laparotomy for gynecologic indications (78 ovarian cancer, 11 endometrial cancer, 19 benign gynecologic disease, 10 other cancers) had biopsies of normal peritoneum for quantitative assessment of neu and EGFR concentrations. Patients undergoing exploration for gynecologic malignancy were found to have significantly higher median neu expression in the peritoneal biopsies than patients with benign gynecologic disease (P = 0.002). Most patients in this study were found to have ovarian cancer, and median peritoneal neu expression was found to be significantly higher in patients with ovarian cancer versus benign ovarian masses (P = 0.0008) or any benign gynecologic disease (P = 0.004). No significant alteration of unbound EGFR was found in peritoneal biopsies of any of the groups of patients. No associations were found for a history of breast cancer, presence of ascites, or menopausal status with alteration of neu or EGFR expression in normal peritoneum. These findings of altered expression of neu in normal tissues of patients with ovarian cancer are suggestive of the presence of proto-oncogene alterations in loco-regional tissues of the peritoneum, such as might be seen if a paracrine influence existed between tumor and peritoneal cells. Alternatively, the alterations may represent subtle alterations of proto-oncogene expression of germ-line tissues.
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PMID:Growth factor expression in normal peritoneum of patients with gynecologic carcinoma. 795 83

Endometrial cancers have been considered to be less prevalent in Japan than in Western countries. However, with the increase in life expectancy, the Westernization of the Japanese diet, and changes in the hormonal environment, the prevalence of the disease has gradually increased even in our country. Similar increases in cancers of the breasts, lungs, colons, and ovaries have been noted in recent years. Much is still unknown regarding the pathogenesis and natural history of endometrial cancer. Although endometrial hyperplasia is considered to be a precancerous lesion of endometrial carcinoma, the relationship between those diseases has not been elucidated to the same degree as that between cervical cancer and cervical dysplasia, or carcinoma in situ. Research findings in genetic oncology have revealed that tumorigenesis involves a multi-step process. It is probable that activation of multiple genes, inactivation of anti-oncogenes, and disappearance of normal inhibitor genes occur in the process of the development of endometrial cancer. The purpose of this study is to elucidate the relationship between oncogenes and the development of endometrial cancer. In addition, the significance of endometrial hyperplasia as a clinical entity is also be evaluated. The roles played by oncogenes in endometrial cancers and endometrial hyperplasias were examined using the most recent molecular biological and immunohistochemical methods. Also, the differences in cellular proliferation and tissue invasiveness were discussed. Results obtained were as follows. Evaluation of cell proliferation (PCNA, FCM) revealed that there was no difference in proliferative activity between atypical hyperplasia and well differentiated adenocarcinoma. Evaluation of oncogene abnormalities (c-myc,c-erbB-2,K-ras,p53) revealed that the development of endometrial cancer was a multistep process involving several oncogenes, as it has been noted in the development of other cancers. Evaluation of extracellular matrix and related factors (cathepsin D, laminin, type IV collagen, tenascin, CD44) showed that tissue invasiveness differed between atypical hyperplasia and well differentiated adenocarcinoma.
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PMID:[Evaluation of the degree of biological behavior in endometrial hyperplasia and endometrial carcinoma: an investigation of proliferative activity, oncogene, and extracellular matrix]. 810 84

This review examines methods of assessing the prognosis of uterine tumors published in the past year. Evaluation of mitosis counts has shown that mitotically active leiomyomas without cytologic atypia follow a benign course; furthermore, the mitotic index does not differentiate endometrial hyperplasia from adenocarcinoma. 'Vascular invasion-associated changes' (VIAC) have been identified as a new prognostic factor for stage 1 endometrial adenocarcinoma. HER-2/neu oncogene expression is also a major prognostic factor in endometrial carcinoma, but positive peritoneal cytology influences survival only in the presence of extrauterine disease. Frozen-section diagnosis and curettings findings at the time of surgery identify poor prognostic factors, allowing limited surgery in patients without poor prognostic indicators. Finally, DNA ploidy as determined by flow cytometry was of prognostic value in uterine sarcomas in one study but not in another when endometrial stromal sarcomas were analysed separately.
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PMID:Pathological findings and prognosis from uterine malignancy. 840 44

HER-2/neu (c-erbB-2) oncoprotein is a transmembrane glycoprotein and may function as a growth factor receptor being involved in the regulation of cell growth and cell transformation. We performed an analysis of 100 patients with endometrial cancer stage FIGO I to IV using an immunoperoxidase technique on formalin-fixed, paraffin-embedded tissue samples in order to determine HER-2/neu oncoprotein expression. HER-2/neu oncoprotein was expressed in the tumors of 21 patients (21%). Clinical stage, histologic stage, histologic grade and death of invasion did not correlate with HER-2/neu oncoprotein expression. We found HER-2/neu oncoprotein in all clinical stages and therefore it does not seem to be a late event in the natural history of endometrial cancer. HER-2/neu oncoprotein expression was associated with poor overall survival (log-rank P-value 0.04).
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PMID:Prognostic value of immunohistochemically detected HER-2/neu oncoprotein in endometrial cancer. 855 2

Using differential polymerase chain reaction (DPCR), dot blot hybridization, and an immunohistochemical technique, we determined the amplification and expression of the c-erbB-2 oncogene in 25 normal, 31 hyperplastic, and 72 malignant samples of the endometrium in 128 patients. Using DPCR, we found amplified c-erbB-2 (two to 12 copies) in two of 25 (8%) normal, 15 of 31 (48%) hyperplastic, and 45 of 72 (63%) malignant samples. These results were closely correlated with those from dot blot (r = 0.78). When comparing the results of DPCR with those of the immunohistochemical method, we noted that the negative findings coincided with one another, i.e., nonamplification was associated with the absence of immunoreactivity. Further analysis showed that amplified c-erbB-2 was found significantly more in complex and atypical hyperplasias versus simple hyperplasias. This indicates that c-erbB-2 may play a potential role in the early development of some endometrial carcinomas. Although no correlation was seen between c-erbB-2 amplification and overall survival in our patients, high-level c-erbB-2 amplification (at least five copies) was significantly associated with the histological grade of endometrial carcinoma and vascular or lymphatic invasion. It is possible that high-level c-erbB-2 amplification identifies a subset of aggressive endometrial carcinoma that involves vascular or lymphatic invasiveness and poor cell differentiation.
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PMID:Amplification and expression of the c-erbB-2 oncogene in normal, hyperplastic, and malignant endometria. 860 33


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