Cases Of Epithelial Ovarian Carcinoma Research Articles

Association of high-grade serous ovarian carcinoma with intraepithelial carcinoma of fallopian tube

Background: The cumulative evidences, both clinicopathological and molecular in the past decade that high-grade serous ovarian carcinoma results from clonal expansion of secretory cells of the distal fallopian tube, rather than ovary. We explored this relationship based on morphological and immunohistochemical studies of a lesion designated “serous tubal intraepithelial carcinoma” (STIC), which closely resembles high-grade ovarian serous carcinoma. This tubal lesion is the plausible origin for pelvic serous carcinomas. Objective: To study the association between ovarian serous carcinoma and STIC. Material and Methods: We studied 44 consecutive cases of epithelial ovarian carcinomas from February 2013 to January 2015, including 29 serous, 12 mucinous, and 3 endometrioid. Complete examination of fallopian tubes from each case was done according to SEEFIM protocol. All the cases were grouped into high-grade serous (27 cases), and non-high-grade serous (17 cases) groups. Immunostaining for p53 and MIB-1 was done on the sections from ovary and fallopian tube. Results: STIC lesion was identified in fallopian tubes from 10 cases of high-grade serous group (37%) while no STIC was identified in non-high-grade serous group. Eighty percent% of the STIC identified were confined to the fimbria of fallopian tube. Results from both groups were compared using chi square test. A statistically significant association was found between high-grade serous carcinoma group and STIC (P = 0.013). Conclusion: STIC coexists with a significant number of high-grade serous carcinoma cases and further studies are needed to elucidate etiological significance of STIC in high-grade serous carcinoma.

Ovarian Transitional Cell Carcinoma Represents a Poorly Differentiated Form of High-grade Serous or Endometrioid Adenocarcinoma

Ovarian transitional cell tumors include Brenner tumors (BTs) and transitional cell carcinoma (TCC; non-BTs) according to the most recent World Health Organization classification. However, it remains a matter of debate whether TCC represents a distinct entity or a morphologic variant of high-grade serous adenocarcinoma (HG-SC). The purpose of this study was to resolve the above question by clarifying the morphologic, immunohistochemical, and molecular features of TCC. We reviewed 488 cases of epithelial ovarian carcinomas and reclassified them on the basis of the most recent World Health Organization classification with the modifications proposed by Köbel and colleagues, and 35 cases of TCC were identified; 25 and 6 TCCs were admixed with HG-SC and endometrioid adenocarcinoma (EC), respectively, and the remaining 4 cases were pure TCC. TCC components were not observed in any clear cell carcinomas or mucinous adenocarcinomas. Only 2 cases of malignant BT were identified. In addition to TCCs, malignant BTs, and related adenocarcinomas, benign and borderline BTs were included in the following immunohistochemical and molecular analyses. Immunohistochemically, pure TCCs, TCCs admixed with HG-SC, and pure HG-SCs were characterized by frequent aberrant p53 expression (diffuse or null pattern) and WT1+/ER+/PR+/IMP2+ immunophenotype, whereas BTs, including benign, borderline, and malignant BTs, were characterized by lack of aberrant p53 expression and WT1-/ER-/PR-/IMP2- immunophenotype. In contrast to the BTs, pure ECs and TCCs admixed with EC showed an ER+/PR+ immunophenotype. Nearly all the tumors with a TP53 gene mutation by molecular analysis showed aberrant p53 staining patterns. In conclusion, TCC is not a distinct entity but a poorly differentiated form of serous or EC, as (1) most TCCs coexist with HG-SC (mostly) or EC (occasionally), and (2) the immunophenotype and molecular features are similar to those of HG-SC or EC but different from those of BTs.

Polymorphisms of Receptor for Advanced Glycation end Products and Risk of Epithelial Ovarian Cancer in Chinese Patients

Background: Given the roles of receptor for advanced glycation end products (RAGE) in the pathogenesis of carcinogenesis, we propose that RAGE polymorphisms may be associated with risk of epithelial ovarian carcinoma (EOC). Method: This case-control study included 190 women over 40 years of age who were diagnosed with primary EOC and 210 healthy control subjects. RAGE gene polymorphisms, including 82G>S,-374T>A,-429C>T,and 1704G>T were determined. Results: We found that only the frequencies of the 82G>S polymorphisms were significantly different between the EOC cases and controls. The 82SS genotype was significantly higher in EOC patients than in controls (37.89% vs. 23.33%,P<0.001). With the 82 GG genotype as reference, the OR for 82SS homozygous carriers reached to 2.65 (95% CI: 1.54-4.58; P =0.0004) after adjustment for age, smoking status, body mass index, family history, usage of contraceptives, tubal ligation history, use of menopausal hormones and menopausal status. The 82S allele carriage presented a higher risk for EOC (OR=1.71; 95% CI, 1.29-2.26; P=0.0002). The polymorphisms of 1704G>T,-374T>A and -429C>T did not affect the EOC risk. Conclusion: This result suggests that the 82G>S polymorphism of RAGE gene may be associated with the susceptibility of EOC.

Expression and clinical significance of GRIM-19 in epithelial ovarian carcinoma

To investigate the expression and clinicopathological features of gene associated with retinoid-interferon mortality-19 (GRIM-19) in epithelial ovarian carcinoma. The expression of GRIM-19 gene in tissues from 138 cases of epithelial ovarian carcinoma, 102 cases of benign ovarian epithelial tumor and 46 cases of normal ovarian tissues were detected by Immunohistochemistry and Western blot methods. Assembled clinical survival data were analyzed with Kaplan-Meier and Cox regression models. The expression level of GRIM-19 in epithelial ovarian carcinoma (3.4 ± 2.0) was lower than that in benign ovarian tumor tissues (4.7 ± 2.9) and that in normal ovarian tissues (7.5 ± 2.2; P < 0.01). The level of GRIM-19 expression was related to the survival time of epithelial ovarian carcinoma patients by Kaplan-Meier analysis (P = 0.002). The shorter survival time of epithelial ovarian carcinoma patients was significantly associated with the level of GRIM-19 expression (P = 0.001), clinical stage (P = 0.001), volume of ascites (P = 0.023) and the largest diameter of the primary tumor lesion (P = 0.044) by Cox regression models. The low expression of GRIM-19 in the epithelial ovarian carcinoma suggests that GRIM-19 may be a key gene involved in its carcinogenesis. The expression level of GRIM-19 may be also an independent prognostic factor for epithelial ovarian carcinoma patients.

Expression of angiogenic chemokines in ovarian clear cell carcinoma

The aim of this study was to assess the expression of angiogenic chemokines (CXCR4/CXCL12) and the vascular endothelial growth factor in ovarian clear cell carcinoma, comparing levels against those in ovarian high-grade serous carcinoma. Tissue microarray samples from 136 cases of epithelial ovarian carcinoma (108 high-grade serous carcinoma and 28 clear cell carcinoma) were reviewed with World Health Organization histological criteria strictly applied to categorize cases according to histological subtype. Only cases without prior exposure to chemotherapy were included. Sections were stained with vascular endothelial growth factor, CXCR4, CXCL12 and assessed using conventional histological scoring (H-scoring). Patients with clear cell carcinoma presented at an early stage of the disease (74% stage 1 and 2) and had a significantly better progression-free (P=0.042) survival than those with high-grade serous carcinoma. Low expression profile of the tested markers was seen in cases of clear cell carcinoma contrary to that seen in high-grade serous carcinoma. The current study reports, for the first time, the difference in expression of a set of angiogeneic prognostic markers between clear cell carcinoma and high-grade serous carcinoma, offering a possible explanation for the apparent chemotherapy resistance. These results are relevant for the design of future clinical studies of first-line treatment for patients with ovarian clear cell carcinoma.

Overexpression of GRP78 Is Associated With Malignant Transformation in Epithelial Ovarian Tumors

Glucose-regulated protein 78 (GRP78) is one of the best-characterized endoplasmic reticulum chaperone proteins. The aim of this study was to explore the potential implications of GRP78 in the development of epithelial ovarian carcinomas (EOCs) and the possible clinical usefulness of GRP78 expression as a prognostic biomarker for EOCs. A total of 133 women were enrolled. This pilot study consisted of 96 cases of EOCs and 37 cases of benign ovarian tumors as controls. The expression of GRP78 protein was studied using tissue microarray technology and immunohistochemistry. Of the 96 invasive carcinomas analyzed, 25 cases (26.0%) showed moderate GRP78 expression and 65 cases (67.7%) showed strong GRP78 expression. Conversely, 17 (45.9%) of the 37 patients with benign ovarian tumors showed no or weak GRP78 staining. Our results demonstrated that GRP78 expression was significantly higher in EOCs than in benign ovarian tumors (P<0.001). However, no statistically significant association was found between GRP78 expression and survival. The present study suggests that GRP78 plays a significant role in malignant transformation of epithelial ovarian tumors and may represent an important biomarker for EOCs.

Pilot Study: Alteration of Deleted in Liver Cancer1 and Phosphorylated Focal Adhesion Kinase Y397 Cytoplasmic Expression and the Prognostic Value in Advanced Epithelial Ovarian Carcinoma

BackgroundDeletion in liver cancer gene (DLC1) and phosphorylated focal adhesion kinase (p-FAK) have recently been reported as metastasis-related genes. However, the roles and prognostic values of their expression in epithelial ovarian carcinomas (EOCs) remain unclear.MethodsThe expression and prognostic value of DLC1 and p-FAK Y397 in EOC were evaluated by immunohistochemistry and multivariate analysis.ResultsLow expression of DLC1 and high expression of p-FAK Y397 were found in the 76 cases of EOC. The expression of DLC1 and p-FAK Y397 were negatively correlated. Multivariate analysis showed that the combination of them was an independent prognostic marker of EOC (P = 0.0319).ConclusionsDLC1 and pFAK Y397 had an association with the clinicopathologic characteristics of EOC. Expression of neither of these genes was a prognostic factor alone, but the combination revealed a significant prognostic value in the 60 cases of advanced stage EOC.

Expression of hSef and FGF-2 in epithelial ovarian tumor

To detect the expression of human similar expression to FGF gene(hSef) and fibroblast growth factor-2(FGF-2) and their correlation with epithelial ovarian tumor. Immunohistochemical SP staining was used to detect the expression of hSef and FGF-2 proteins in 31 cases of epithelial ovarian carcinoma (EOC), 18 cases of benign epithelial tumor (BET), 10 cases of normal ovarian (NO) tissues collected from July 2007 to May 2008. The expression of hSef mRNA in 24 cases of EOC, BET and NO collected from July 2008 to May 2009 were analyzed by RT-PCR. The results of immunohistochemical study showed that the expression of hSef in the EOC tissues were significantly lower than that in the NO and BET (P < 0.001). However, the expression of FGF-2 was higher (P = 0.002). The expression of hSef had a negative correlation with FGF-2 (r(s) = -0.324, P = 0.012). The RT-PCR results showed that there was a gradually declined trend of expression of hSef in NO, BET to EOC (P < 0.001), but the expression of FGF-2 in NO, BET to EOC was gradually increased (P < 0.001), with a significant negative correlation (NO: r(s) = -0.910, P < 0.001; BET: r(s) = -0.859, P < 0.001; EOC: r(s) = -0.888, P < 0.001). The expression of hSef is decreased in epithelial ovarian carcinoma tissue, but the expression of FGF-2 is increased. It is likely that low hSef expression is related to the the carcinogenesis and development of epithelial ovarian carcinoma by suppressing the promoting effects of FGF-2 to cell proliferation.

Immunohistochemical analysis of 17β-hydroxysteroid dehydrogenase isozymes in human ovarian surface epithelium and epithelial ovarian carcinoma

Epidemiological studies have indicated a relationship between gonadal steroid hormones, primarily estrogens, and epithelial ovarian carcinoma. In situ estrogen metabolism and synthesis have been considered to play important roles in the development of the progression of epithelial ovarian carcinoma. 17β-Hydroxysteroid dehydrogenases (17β-HSDs) are a group of intracellular isozymes catalyzing interconversions between estradiol (E2) and estrone (E1). In the last step of steroidogenesis, 17β-HSD type 1 catalyzes the 17β-reduction and produces E2 from E1. The oxidative enzymes known as types 2, 4, and 8 are potent estrogen-inactivating enzymes that convert E2 to E1. Here we report the immunoexpression of 17β-HSD types 1, 2, 4, and 8 in normal human ovarian surface epithelium (OSE) and epithelial ovarian carcinoma. For this study, novel polyclonal antibodies were generated against each type of 17β-HSD. Of the six normal OSE cases investigated, 17β-HSD types 1, 4, and 8, but not type 2, were found in the cytoplasm of epithelial cells. In 58 cases of epithelial ovarian carcinoma (45 serous, 4 endometrioid, 4 mucinous, and 5 clear cell), estrogen-inactivating 17β-HSDs were commonly found (type 2, 84.5%; type 4, 82.8%; type 8, 86.2%), whereas type 1 was detected in only 10 cases (17.2%). These results indicate that 17β-HSDs may be involved in the protective and/or suppressive effects against the estrogen-dependent proliferation of epithelial ovarian carcinoma.

Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium

We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type. Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site. The five polymorphisms were not associated with ovarian carcinoma overall (P(trend) > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; P(heterogeneity) = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05). TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification. Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology.

Uterine metastases in ovarian carcinoma: frequency and survival in women who underwent hysterectomy

Possible reasons for hysterectomy in the initial surgical management of advanced invasive epithelial ovarian carcinoma (EOC) might be a high frequency of uterine involvement and its impact on survival. The aim of the present study was to describe the frequency of uterine involvement and its association with survival in an unselected population of EOC patients who underwent hysterectomy. All incident cases of EOC diagnosed in Israeli Jewish women between March 1994 to June 1999, were identified within the framework of a nationwide case-control epidemiological study. The target population of the present report includes all stage II-IV EOC patients who had a uterus at the time of diagnosis. Of the 822 such patients, 695 fulfilled the inclusion criterion. Excluded were 141 patients for various reasons. The present analysis is based on the remaining 554 patients. Uterine involvement was present in 291 (52.5%) of the patients and it was macroscopic in only 78 (14.1%). The serosa was the most common site of isolated metastases. Multivariate analysis showed that advanced stage significantly increased the risk for uterine involvement. The overall median survival with any uterine involvement was significantly lower compared to those with no involvement (38.9 months vs. 58.0 months; p<0.001). There is an association between uterine involvement, whether macro- or microscopic, and lower survival even after hysterectomy although residual tumor could not be included in the analysis. Further studies are required to establish whether uterine involvement itself is an unfavorable risk factor or merely a marker of other unfavorable prognostic factors.

Performance of a biomarker panel to identify malignancy within a pelvic mass population

5566 Background: We previously reported the performance of biomarker combinations that displayed utility in identifying ovarian cancer from normal sera and in monitoring for disease recurrence. In this study, we evaluated the performance of a subset of these markers in differentiating ovarian cancer from benign pelvic mass. Methods: Pre-operative serum samples were prospectively collected from 254 patients undergoing surgical evaluation for differential diagnosis of a pelvic mass. Pathology showed 76 cases of epithelial ovarian carcinoma (EOC), 17 borderline tumors, 11 other gynecologic cancers, and 150 benign masses. 18 (23.7%) of the EOC patients had stage I tumors; 6 (7.9%) stage II; 44 (57.9%) stage III; and 8 (10.5%) stage IV. Serum levels of CA125, HE4, glycodelin, SLPI, MMP7, and Plau-R were ascertained. Biomarker performance was evaluated by a logistic regression model and leave one out cross-validation analysis. All calculations compared the benign vs. EOC and borderline tumor populations. Results: Individual biomarker sensitivity ranged from 28% to 77% at 85% specificity. The combination of CA125, HE4 and glycodelin exhibited the highest overall performance in identifying malignancy from benign masses, demonstrating 80% sensitivity, 80% specificity in patients &lt;55 years, and 89% sensitivity, 80% specificity in patients ≥55. Total cohort performance was 85% sensitivity and 80% specificity. Glycodelin identified 7/22 CA125 and HE4 double negative patients, 5/7 of these patients were early stage (borderline, I or II), while only adding 4/150 false positive cases. Conclusions: Biomarker analysis within this test cohort demonstrates potential clinical utility in the differential diagnosis of pelvic mass patients, especially for the detection of early stage disease. The addition of glycodelin improved the detection of early stage cancer in sera that were negative for both HE4 and CA125. [Table: see text]

Primary Carcinoma of the Fallopian Tube and Epithelial Ovarian Carcinoma: A Case Control Analysis

Primary carcinoma of the fallopian tube (PCFT) has been traditionally assessed and treated following epithelial ovarian carcinoma (EOC) guidelines despite the paucity of supporting data. A previous population-based study reported a better prognosis for PCFT, but no case match data has been published evaluating clinical parameters and outcomes. To analyze clinical similarities and differences between women with PCFT and EOC in case control fashion, the investigators examined records in the tumor registry database of the University of Iowa Hospitals and Clinics from 1991 to 2001. Cases of PCFT were matched with EOC controls according to the chronology of diagnosis. Each case of PCFT was matched with the next two cases of EOC with an 1-year limit for finding the closest match. Priority was given to stage of disease and histological grade, followed by histology. Twenty-eight cases of PCFT were matched with 56 cases of EOC. PCFT patients were 7 years older at diagnosis than the EOC patients (mean age, 67 versus 60 years, P = .005). No significant differences between the two diseases were found in the prediagnosis use of oral contraceptives (P = .38); body mass index (P = .5); percentage of positive nodes (P = .19); or survival based on Kaplan-Meier analysis (P = .5). The investigators conclude that the apparent lack of differences between PCFT and EOC in clinical parameters or survival indicates that PCFT should be treated according to protocols designed for EOC.

Prospective study of physical activity and the risk of ovarian cancer.

Available studies on physical activity and ovarian cancer have produced inconsistent findings, with some previous studies reporting a positive association between vigorous physical activity and ovarian cancer risk. We prospectively investigated the relations of self-reported moderate and vigorous physical activity to ovarian cancer in a cohort of 96,216 US women aged 51-72 years at baseline, followed from 1996-1997 to 31 December 2003. During seven years of follow-up, we documented 309 cases of epithelial ovarian carcinoma. In analyses adjusted for age, the relative risks (RRs) of ovarian cancer for individual and joint combinations of moderate and vigorous physical activity such as entirely inactive, neither moderate nor vigorous physical activity, moderate physical activity only, vigorous physical activity only, and both moderate and vigorous physical activity were 0.88, 1.0 (reference), 0.89, 1.05, and 1.08 (95% confidence interval (CI) = 0.81-1.43, respectively. After multivariate adjustment, the relation was essentially unchanged (RR comparing women with both moderate and vigorous physical activity to those with neither moderate nor vigorous physical activity = 1.10; 95% CI = 0.82-1.48). The null association between physical activity and ovarian cancer persisted in subgroups of women as defined by body mass index, parity, oral contraceptive use, menopausal hormone therapy, family history of ovarian cancer, and other variables (all p values for interaction >0.05). Neither moderate nor vigorous physical activity showed a statistically significant association with ovarian cancer in this large cohort of women.

Seven Cases of Epithelial Ovarian Carcinoma with Brain Metastasis

To summarize the clinical characteristics, treatment, and prognosis of brain metastasis in patients with epithelial ovarian carcinoma. Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosis-affecting factors. Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66% (7/1055). Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases. All the patients were diagnosed at late stage, 6 cases with the International Federation of Gynecology and Obstetrics (FIGO) stage IIIc and 1 with FIGO stage IV. The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7 +/- 20.0 months (range, 23-73 months). Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases. Fifty-seven percent of patients presented extracranial metastasis. Serum CA125 played a role in monitoring reoccurrence and brain metastases. The average survival time was about 12 months. Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy. As a rare condition, brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival. However, brain metastasis indicates bad prognosis which can be improved by combined therapy.

0220: Analysis On Treatment and Prognosis of 15 Cases of Epithelial Ovarian Carcinoma Complicated with Bowel Obstruction

0220: Analysis On Treatment and Prognosis of 15 Cases of Epithelial Ovarian Carcinoma Complicated with Bowel Obstruction

Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P < 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.

Expression of the c-Met in advanced epithelial ovarian cancer and its prognostic significance

The purpose of this study was to evaluate the prognostic significance of c-Met expression in advanced cases of epithelial ovarian carcinoma. Paraffin-embedded tissues from 41 stage IIIC primary ovarian adenocarcinoma were stained immunohistochemically for c-Met expression. The expression of c-Met was correlated with conventional clinicopathologic parameters and with overall survival of the patients. c-Met expression was found in 60.9% of cases. This clinicopathologic study showed that epithelial ovarian carcinomas with c-Met expression had higher histologic tumor grade and were more frequently associated with para-aortic lymph node metastasis (P&lt; 0.05). In multivariate analysis, c-Met expression remained as a statistically significant predictor for survival with histologic grade. The patients with stage IIIC epithelial ovarian cancers whose tumors expressed c-Met were more likely to have high-grade tumors, have more para-aortic lymph node involvement, and have a significantly worse overall survival than those whose tumors were c-Met negative. In conclusion, c-Met expression might be a potential prognostic marker for patients with advanced-stage epithelial ovarian cancers.

StAR and progesterone producing enzymes (3β‐hydroxysteroid dehydrogenase and cholesterol side‐chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: Immunohistochemical and real‐time PCR studies

Steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase enzyme (3beta-HSD) are all involved in the transport of cholesterol and production of progesterone. In situ production of sex steroids including progesterone have been considered to play important roles in pathogenesis and/or development of common epithelial ovarian carcinomas. In this study, StAR, P450scc, and 3beta-HSD were immunolocalized in 100 cases of ovarian carcinoma and results were then correlated with clinicopathological and prognostic parameters of individual patients including status of progesterone receptor (PR) in tumor cells. Results of immunohistochemistry were further characterized by real-time PCR analysis in 20 cases of epithelial ovarian carcinomas in which frozen tissues were available for examination. StAR, P450scc, and 3beta-HSD immunoreactivity was detected predominately in the cytoplasm of carcinoma cells. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. StAR, P450scc, and 3beta-HSD H scores demonstrated significant inversed statistical correlation with FIGO stage, residual size of the tumor, and Ki67 LI. A positive statistically significant correlation was detected between StAR H score and PR-B LI. Multivariate statistical analysis demonstrated that the status of intratumoral StAR, FIGO stage, and residual tumor size all turned out to be independent prognostic factors for the clinical outcome of the patient. The presence of StAR, a cholesterol transporter for steroidogenesis in human epithelial ovarian carcinoma, may reflect the ability of these tumors to produce progesterone in situ that could influence biological behavior of these tumors, especially through progesterone dependent inhibition of tumor cell proliferation.

Nucleolar Organizer Regions as a Prognostic Indicator in Epithelial Cancers of the Ovary

Recent studies have shown that quantification of silver-stained nucleolar organizer region associated proteins (AgNORs) is correlated with ploidy and proliferative activity in several neoplasms. The prognostic value of this marker, however, has not been well defined in epithelial ovarian carcinomas (EOCs). We studied 84 cases of EOCs in an attempt to assess the potential prognostic significance of AgNORs and to compare the results with other prognostic factors in EOCs. Clinical, operative and treatment details, and follow-up data were recorded for each case. In univariate analysis, a highly significant correlation of AgNOR count with clinical stage (p < 0.01), histologic grade (p < 0.05), response to chemotherapy (p < 0.05), and biologic behavior (p < 0.01) was found. High AgNOR counts were observed in late stage (III and IV) tumors, grade 3 carcinomas, tumors in patients with partial response to chemotherapy, progressive disease, recurrence, or death from tumor. In multivariate analysis, AgNOR count at cut off 3.5 was found to be the third prognostic variable after response to therapy and stage. These observations suggest that AgNOR count holds promise for prediction of tumor aggressiveness in EOCs. However, its role as an independent prognostic variable of patient survival remains questionable.