Prophylactic oophorectomy: a morphologic and immunohistochemical study.
ABSTRACT The tumorigenesis of ovarian carcinoma is poorly understood. The authors studied morphologic features and immunohistochemical expression patterns of neoplasia-associated markers in prophylactically removed ovaries, normal ovaries, and papillary serous ovarian carcinomas to identify possible preneoplastic changes in ovarian surface epithelium.
Morphologic features and immunohistochemical expression patterns of CA-125, Ki-67, p53, E-cadherin, and Bcl-2 were evaluated in 21 normal ovaries, 31 ovaries that were removed prophylactically for increased carcinoma risk, and 7 ovarian papillary serous carcinomas. Representative slides from formalin-fixed, paraffin-embedded tissue blocks were submitted to immunohistochemical staining and were evaluated independently by three gynecologic pathologists. For statistical analyses, Fisher exact tests, multivariate analyses, Spearman rank correlation coefficients, Wald statistics, Kruskal-Wallis tests, and Mann-Whitney tests were used. Immunohistochemical staining results were correlated with morphologic findings.
The authors found progressive increases in reactivity with the lowest expression in normal ovarian epithelium, stronger expression in epithelium from prophylactically removed ovaries, and the highest expression in carcinomas for Ki-67 and p53. A similar trend was observed for CA-125. Positivity for Ki-67 and p53 was seen predominantly in the epithelium of inclusion cysts and deep invaginations, including those areas that had been identified as hyperplastic or dysplastic on routine hematoxylin and eosin-stained sections.
The current results suggest biologic/molecular evidence for the existence of preneoplastic changes in ovarian surface epithelium and support the previously proposed concept of ovarian dysplasia. Subtle morphologic alterations of the ovarian epithelium may be biologically significant.
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ABSTRACT: Sections of formalin-fixed and paraffin-embedded tissue specimens of 11 normal ovaries and tubes, 13 tubo-ovarian abscesses, 3 tubal carcinomas, and 115 ovarian tumors were investigated by immunohistochemistry. CA 125 and CA 19-9 were demonstrated with monoclonal antibodies, CEA with polyclonal antibodies. The tissue expression was visualized by the avidin-biotin method. In the germinal epithelium of all ovaries no tumor marker was confirmed. In 4 out of 11 tubes the epithelium was CA 125 positive, in 2 out of 11 cases CA 19-9 positive. Nine out of 13 tubo-ovarian abscesses were CA 125 and 5 out of 13 were CA 19-9 positive in their epithelium. Elevated serum levels of these markers might be due to expression via the epithelial cell of the inflamed tube. All normal and inflammatory adnexal tissues were CEA negative. In serous tumors and undifferentiated carcinomas, CA 125 was most frequently confirmed (85 and 70%, respectively). All mucinous tumors were CA 125 negative. The most frequently confirmed tumor marker was CA 19-9 (77%). In endometrioid tumors, CEA was most frequent (44%). In 42% of the borderline tumors and carcinomas only one marker was demonstrated, in 7% none. Here, immunohistochemistry may indicate the most adequate marker. Tumor marker expression was markedly heterogenous: tumor areas with strong, weak, and no reaction were adjacent. The tumor markers revealed no specificity for malignancy or disease.Gynecologic Oncology 04/1989; 32(3):297-302. · 3.93 Impact Factor
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ABSTRACT: We report on our continued experience with an interactive morphometric method recently introduced by us for the definition and diagnosis of ovarian dysplasia vs. normal or malignant epithelium. The main quantitative differences between these three diagnostic categories are based on 1) cytology of the nuclei (nuclear area, circularity factor, maximum chord) and 2) on stratification (distances of nuclear centers to the basement membrane and number of cells per unit length of basement membrane). We implemented our approach on live video images viewed on a monitor overlaid with a touch sensitive screen by one of two interactive procedures: 1) by tracing nuclear profiles (procedure DRAW) or 2) by tracing the basement membrane and touching the center of all nuclei (procedure NU-MEAS). In all cases statistical analysis was performed on a string of multiple variables by stepwise discriminant analysis. Now we have straightened our data basis and are able to obtain diagnosis of unknown samples with very high posterior probabilities. Both procedures are effective but NU-MEAS requires the least effort and seems to give the best statistics.Pathology - Research and Practice 12/1989; 185(5):680-5. · 1.21 Impact Factor
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ABSTRACT: This study updates findings regarding the effects of prophylactic surgery, chemoprevention, and surveillance on the survival and quality-adjusted survival of women who test positive for BRCA1/2 mutations. Markov modeling of outcomes was performed in a simulated cohort of 30-year-old women who tested positive for BRCA1/2 mutations. The model incorporated breast and ovarian cancer incidence rates from the literature and mortality rates from the Surveillance, Epidemiology, and End Results Program. Quality adjustment of survival estimates were obtained from a survey of women aged 33 to 50 years. Sensitivity analyses were performed of varied assumptions regarding timing and effects of preventive measures on cancer incidence and adverse effects. A 30-year-old woman could prolong her survival beyond that associated with surveillance alone by use of preventive measures: 1.8 years with tamoxifen, 2.6 years with prophylactic oophorectomy, 4.6 years with both tamoxifen and prophylactic oophorectomy, 3.5 years with prophylactic mastectomy, and 4.9 years with both surgeries. She could prolong her quality-adjusted survival by 2.8 years with tamoxifen, 4.4 years with prophylactic oophorectomy, 6.3 years with tamoxifen and oophorectomy, and 2.6 years with mastectomy, or with both surgeries. The benefits of all of these strategies would decrease if they were initiated at later ages. Women who test positive for BRCA1/2 mutations may derive greater survival and quality adjusted survival benefits than previously reported from chemoprevention, prophylactic surgery, or a combination. Observational studies and clinical trials are needed to verify the results of this analysis of the long-term benefits of preventive strategies among BRCA1/2-positive women.Journal of Clinical Oncology 06/2002; 20(10):2520-9. · 18.04 Impact Factor