Rita I. Demopoulos

Contralateral ovary in unilateral ovarian carcinoma: a search for preneoplastic lesions.

Contralateral ovaries from patients with unilateral ovarian carcinoma were examined and compared to ovaries from age-matched control patients without ovarian carcinoma. The number of inclusion cysts were increased in ovaries from patients with ovarian carcinoma compared to the controls (p < 0.01). In addition, inclusions from cases with ovarian carcinoma showed serous differentiation more frequently than the controls (p < 0.01; odds ratio = 10.0; 95% confidence interval = 1.2-78.1). An age-related increase in the number of inclusion cysts was seen in the study group but not in the control group. These findings support a role of surface inclusion cysts in the genesis of ovarian carcinoma.

Secondary ovarian carcinoma: a clinical and pathological evaluation

SummaryA retrospective clinical and pathological analysis was performed of 96 patients with secondary ovarian carcinoma diagnosed between January 1972 and June 1985 at New York University Medical Center. Secondary tumors accounted for 17.4% (96/553) of ovarian malignancies. The most common sites of origin were breast (32 cases), unilateral ovary (with contralateral metastases) (20), endometrium (14), colon (12), stomach (6), cervix (2), ileum (2), and I each for 8 additional sites. The patients ranged in age from 19 to 87 years, averaging 54.8 years, and 55 patients were postmenopausal. Ninety percent of the patients had extraovarian metastases at the time of abdominal surgery. The ovarian metastases tended to be bilateral for breast, colon and stomach, and unilateral for endometrial and ovarian primary sites. The metastases tended to be solid except for colon. The overall survival rate was 24.1% at 5 years and 7.1% at 10 years. Comparison of median survival times for the various major primary sites showed a significant overall difference (p = 0.04) and was as follows: gastric primary 0.79 years, breast 1.9 years, ovary 2.0 years, colon 3.0 years, and endometrium 3.4 years. Postmenopausal patients with unilateral ovarian carcinoma and contralateral metastases had a significantly (p = 0.04) longer median survival time (4.2 years) than analogous premenopausal patients (1.3 years). For breast and endometrium, menopausal status was not significantly associated with survival differences. These findings should prove useful in the differential diagnosis of ovarian tumors and in the medical management of these patients.

Expression of the cell cycle inhibitor p27KIP1 is a new prognostic marker associated with survival in epithelial ovarian tumors

This case-control study was designed to identify factors associated with long-term survival. We examined two groups of patients with epithelial ovarian cancer, one group of long-term survivors (> 5 years) and one group of short-term survivors (< 2 years), for levels of expression of p53 and p27KIP1 proteins (as both proteins have been shown to be independent prognostic markers in tumors other than ovary) and the relationship with patient survival. Our findings show that p27KIP1 expression, in contrast to p53 expression, is positively associated with long-term survival in univariate analysis (P = 0.001), in analyses stratified by residual disease (P = 0.02) or performance status (P = 0.02), the two strongest prognostic factors for ovarian cancer, as well as multivariate analysis (P = 0.002) adjusting simultaneously for age, tumor stage, residual disease, performance status, and grade of differentiation. Therefore, immunostaining for levels of p27KIP1 expression may have potential as a new prognostic factor in the management of ovarian cancer.

Effect of Highly Active Antiretroviral Therapy on Survival in Patients With AIDS-Associated Pulmonary Kaposi’s Sarcoma Treated With Chemotherapy

PURPOSE Kaposis sarcoma (KS) is the most common AIDS-related malignancy. Pulmonary involvement by KS (PKS) has carried a poor prognosis with median reported survival ranging from 3 to 10 months. We studied whether the introduction of highly active antiretroviral therapy (HAART; triple antiretroviral therapy including a protease inhibitor and two reverse transcriptase inhibitors) has been associated with improved survival for AIDS patients with PKS. PATIENTS AND METHODS A retrospective study was performed of 37 consecutive patients with PKS and human immunodeficiency virus infection in the tumor registry at a large municipal hospital in New York City between 1994 to 1997. There were 16 patients from 1994 to 1995 (pre-HAART period) and 21 patients from 1996 to 1997 (post-HAART period). The primary end point was survival, which was defined as time from start of chemotherapy until death from any cause. RESULTS Patients were analyzed by the date of diagnosis (pre- v post-HAART period) and whether or not they received HAART. Kaplan-Meier analysis showed significantly better survival in patients diagnosed in the post-HAART period (P =.0025). Additional Kaplan-Meier analysis indicated that patients on HAART had substantially better survival (P <.0001). Cox multivariate analyses showed that HAART therapy was associated with a reduced risk of death (hazard ratio = 0.09; 95% confidence interval, 0.03 to 0.69). CONCLUSION In patients with AIDS-associated PKS and undergoing chemotherapy, administration of HAART was associated with increased survival.

The accuracy of frozen section in the diagnosis of ovarian neoplasms

In a retrospective study to determine the accuracy of frozen section diagnoses in ovarian neoplasms, the results of consecutive frozen section diagnoses of 311 ovarian neoplasms from two institutions, New York University Medical Center and State University of New York Medical Center at Brooklyn, from 1980 through 1989 were compared with the final diagnosis results following extensive sampling on permanent sections. The final diagnosis was assumed to be correct for purposes of this study. Ovarian neoplasms were correctly diagnosed on frozen section as either benign or malignant in 292 patients (accuracy of 93.8%). Frozen section diagnoses were incorrect in 11 patients (3.5%). Frozen section diagnosis was deferred in 8 instances (2.6%). The positive predictive value was 100%. The negative predictive value was 95.3%, specificity 100%, and sensitivity 86%. There were no false positives. Of the 11 false negative frozen section diagnoses, 9 (82%) were due to limited sampling for frozen section. We therefore suggest that careful examination with sampling of any suspicious lesions be carried out at the time of surgery for patients with benign frozen section diagnosis, since this may avoid a second staging laparotomy, if the final diagnosis is malignant.

Gonadotropic hormone binding to human ovarian tumors

A variety of normal human ovarian tissues as well as benign and malignant human ovarian neoplasms have been examined in vitro for the presence of gonadotropin binding sites and gonadotropin-stimulable cAMP production, in order to determine whether gonadotropic hormones have an effect on ovarian tumors. Binding of either FSH or hCG, or both, was demonstrated in several tumors from each of the histologic subgroups of primary ovarian tumors, including epithelial, sex cord-stromal, and germ cell types. Cyclic AMP stimulation was found in one tumor of sex cord-stromal origin, in two of epithelial origin, in two of germ cell origin, and in one tumor-like condition, pregnancy luteoma. Additional biochemical studies are needed to characterize receptor sites and to relate them to histologic features, growth behavior in vivo, and serum gonadotropin levels.

Estrogen and progesterone receptor expression in endometrial polyps.

Endometrial polyps are a frequent cause of abnormal uterine bleeding, but their pathogenesis is poorly understood. This study was undertaken to investigate if endometrial polyps result from localized overexpression of estrogen receptors (ERs) or reduced expression of progesterone receptors (PRs). Fourteen cases of endometrial polyps, in which normal cycling endometrium was also present on the same slide, were immunostained for ERs and PRs. Percentages of positive cells in glands and stroma for each receptor were subjectively assessed to the nearest 5%. The intensity of staining was recorded on a scale from 1+ to 4+. The level and intensity of staining in polyps were compared with the staining in normal endometrium. Fewer stromal cells in polyps expressed ERs and PRs compared with cycling endometrium (% ER = 55.9 +/- 25.8 vs. 74.3 +/- 25.8, p = 0.03; % PR = 56.1 +/- 28.2 vs. 87.5 +/- 10.1, p = 0.002). Stroma in polyps also had significantly reduced intensity of staining for PRs, but not for ERs (intensity PR = 2.7 +/- 1.4 vs. 3.5 +/- 0.7, p = 0.015; intensity ER = 2.1 +/- 0.7 vs. 2.4 +/- 0.8, p = 0.45). There were no significant differences in expression of ERs and PRs in the endometrial glands in endometrial polyps compared with normal endometrium (% ER = 75.4 +/- 32.5 vs. 70.7 +/- 39.2. p = 0.25; % PR = 79.6 +/- 32.8 vs. 80.4 +/- 34.4, p = 0.8; intensity ER = 2.7 +/- 0.9 vs. 2.4 +/- 1, p = 0.15; intensity PR = 2.9 +/- 1.4 vs. 3.4 +/- 0.7, p = 0.15). We conclude that endometrial polyps may result from a decrease in ER and PR expression in stromal cells. Because of these receptor-negative stromal cells, endometrial polyps may be relatively insensitive to cyclic hormonal changes.

Proliferating cell nuclear antigen (cyclin) expression in normal and abnormal cervical squamous epithelia.

Expression of Proliferating cell nuclear antigen (PCNA) was evaluated in formalin-fixed, paraffin-embedded normal and abnormal cervical squamous epithelia using immunoperoxidase stains and PC10 monoclonal antibody to PCNA. PCNA was exclusively expressed in the parabasal and basal layers of normal ectocervix and a similar pattern was seen in nine of the 11 cases with squamous metaplasia. Examples of cervical dysplasia showed expression in higher layers of cervical epithelium, corresponding to the degree of dysplasia. Increased staining was seen in condylomas and markedly reduced staining with atrophy. The percentage of basal cells that stained increased progressively from atrophic to normal, to condylomatous, to dysplastic epithelia. Proliferative activity can be satisfactorily assessed in formalin-fixed cervical epithelia using PC10 PCNA antibody. This assessment can be of potential diagnostic use in difficult cases.

The prognostic significance of nuclear DNA content in malignant epithelial tumors of the ovary

Recent studies have indicated that the nuclear DNA content of certain malignant neoplasms can be used as an adjunct in predicting their biologic behavior. The DNA content of 99 ovarian carcinomas was determined by flow cytometric analysis of nuclei obtained from paraffin‐embedded tissue. Of the 99 tumors, 51 were diploid and 48 showed one or more aneuploid peaks. The 5‐year survival for patients with diploid tumors (50%) was significantly higher than for patients with aneuploid tumors (22%) (P <0.01). Other factors which significantly affected survival were clinical stage (P <0.001), tumor pattern grade (P <0.01), DNA index (P <0.01), the presence of ascites (P < 0.001), peritoneal carcinomatosis (P <0.0001), and residual tumor at second‐look laparotomy (P <0.05). Diameter of the primary ovarian tumor, diameter of the largest peritoneal implant before debulking, and the percent S‐phase had no significant correlation with survival. Of 16 patients with aneuploid tumors who underwent second‐look laparotomy, nine (56%) had residual tumor, compared to six of 22 of patients with diploid tumors (27%). Of seven patients with aneuploid tumors and a negative second‐look laparotomy, four (57%) died from recurrent tumor. By comparison, of 16 patients with diploid tumors and a negative second‐look laparotomy, only four (25%) died from recurrent tumor. The determination of DNA ploidy in ovarian carcinomas may be used as an adjunct in predicting tumor behavior, response to chemotherapy, and late recurrence of disease.

Analysis of multiple prognostic factors in patients with stage IB cervical cancer: Age as a major determinant

To evaluate the prognostic importance of age in patients with Stage IB cervical cancer we reviewed the results of 131 patients treated between 1974 and 1985. Patients ranged in age from 25 to 87 (mean 48) and were followed for a median of 65 months. One hundred twenty-five patients had complete follow-up information for survival analysis. Patients were divided into two groups; Group A comprising 43 patients less than or equal to age 40 and Group B comprising 88 patients greater than age 40. Both Group A and Group B patients were comparable with respect to all covariables studied. The 5-year actuarial survival for the 125 patients studied was 80%, whereas that for Group A (42 patients) and Group B (83 patients) was 54% and 91%, respectively (p = .0001). The 5-year survival for 100 surgical patients was 79% and that for Group A (36 patients) and Group B (64 patients) was 53% and 90%, respectively (p = .0001). The 5-year survival for 25 patients treated with curative RT was 65% and that for Group A (six patients) and Group B (19 patients) was 42% and 90%, respectively (p = .005). Eighteen patients were treated with adjuvant RT following surgery and their 5-year survival was 69% with three out of nine Group A and nine out of nine Group B patients alive at 65 months (p = .004). In 18 patients with pelvic nodal involvement, the 5-year survival was 48% compared to 84% in patients with negative nodes (p = .007). The difference in survival at 5 years between Group A (nine patients) and Group B (nine patients) with positive nodes was 25% and 75%, respectively. Finally, there was an increase in both local and distant failure in Group A patients. Our data illustrate that age has a profound influence on survival in women with Stage IB cervical cancer independent of potentially confounding variables.