Features Of Epithelial Ovarian Cancer Research Articles

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer.

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

Utility of Serum miR-125b as a Diagnostic and Prognostic Indicator and Its Alliance with a Panel of Tumor Suppressor Genes in Epithelial Ovarian Cancer.

MicroRNAs (miRNAs) have been found to be dysregulated in epithelial ovarian cancer (EOC) and may function as either tumor suppressor genes (TSGs) or as oncogenes. Hypermethylation of miRNA silences the tumour suppressive function of a miRNA or hypermethylation of a TSG regulating that miRNA (or vice versa) leads to its loss of function. The present study aims to evaluate the impact of aberrant microRNA-125b (miR-125b) expression on various clinicopathological features in epithelial ovarian cancer and its association with anomalous methylation of several TSGs. We enrolled 70 newly diagnosed cases of epithelial ovarian cancer, recorded their clinical history and 70 healthy female volunteers. Serum miR-125b levels were determined by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and the methylation status of various TSGs was investigated by methylation specific PCR. ROC curves were constructed to estimate the diagnostic and prognostic usefulness of miR-125b. The Kaplan—Meier method was applied to compare survival curves. Expression of miR-125b was found to be significantly upregulated (p<0.0001) in comparison with healthy controls. The expression level of miR-125b was found to be significantly associated with FIGO stage, lymph node and distant metastasis. ROC curve for diagnostic potential yielded significant AUC with an equitable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status and survival. The expression of miR-125b also correlated significantly with the hypermethylation of TSGs. Our results indicate that DNA hypermethylation may be involved in the inactivation of miR-125b and miR-125b may function as a potential independent biomarker for clinical outcome in EOC.

Clinicopathologic features of epithelial ovarian cancer

Objectives: This retrospective study was conducted at the Clinical Oncology Department of Mayo Hospital with the objectives to find out the frequency of different clinicopathologic features and to see the pattern of treatment and its outcome. Patients and methods: From 2000 to 2004, 375 patients were seen at the Department of Clinical Oncology, Mayo hospital, Lahore. A proforma was designed to document the age, parity, histopathology, stage, grade, clinical features, and family history. The information was obtained from the medical record section. Stage was assigned according to FIGO staging system. All patients with histopathologically proven epithelial ovarian cancer were included. Results: Epithelial ovarian cancer constituted 8.4 % of all female cancers. The median age at presentation was 51 years (range, 21-75 years). All patients were symptomatic before the diagnosis, with ascites being the most common single manifestation (38.4 %) and in patients with multiple signs and symptoms abdominal sym ptoms were most commonly seen (71.5 %). Median pre operative CA125 level was 218 U/ml. ).Optimal cytoreduction was seen in 36.5 % only, and 63.5% patients presented after sub-optimal cytoreduction. Majority of the patients (82.7%) presented in late stages (III &amp; IV) and only 17.3 % in early stages (I&amp;II). Most common histopathologic type of invasive cancer was serous cystadenocarcinoma , seen in 247(72.4%) patients. Endometrioid tumors were seen in very few (3.8 % ).High grade tumors were the most common. Most women were multiparous and only 16.5% were nulliparous. Post operative treatment primarily included cisplatin based combination chemotherapy. One hundred and twenty seven patients were re treated for recurrent or residual disease and 68 were referred for secondary cytoreduction and were given second line therapy subsequently. Conclusion: Epithelial ovarian cancer is not a silent disease, most patients are symptomatic and present in an advanced stage. In majority of the patients optimal cytoreduction is not achieved. Cystadenocarcinoma is the predominant histology and the endometrioid variety is seen only in few.

The conglomeration of diagnostic, prognostic and therapeutic potential of serum miR-199a and its association with clinicopathological features in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is the most lethal cause of morbidity and mortality worldwide. miRNA deregulation evinces a remarkable role in ovarian cancer tumorigenesis. miRNA-199a (miR-199a) is known to be involved in cancer development and progression. Although miR-199a has been studied in various cell types, its correlation with clinicopathological features in EOC has not been documented. In this study, we identified the clinicopathological hallmarks which might be perturbed due to the downregulation of serum miR-199a in EOC. Seventy serum samples from histopathologically confirmed EOC patients and 70 controls were collected. Total RNA from serum was isolated by Trizol method, polyadenylated and reverse transcribed into cDNA. Expression level of miR-199a was detected by using miRNA qRT-PCR. Relative expression was determined with matched controls using U6 snRNA as reference. Level of miR-199a expression was compared with distinct clinicopathological features. Expression of miR-199a was found to be significantly downregulated in comparison with matched normal controls. The expression level of miR-199a was found to be significantly associated with tumor stage, lymph node metastasis, and distal metastasis. Receiver operating characteristic (ROC) curve for diagnostic potential yielded significant area under the curve (AUC) with a considerable sensitivity and specificity. ROC curves for prognosis yielded significant AUCs for histological grade, distal metastasis, lymph node status, and survival. Our findings suggest that miR-199a downregulation might be a potential indicator for disease progression promoting the aggressive tumor progression and be identified as a diagnostic marker to predict the prognosis and survival in EOC patients.

High levels of EGFR expression in tumor stroma are associated with aggressive clinical features in epithelial ovarian cancer.

PurposeThe aim of this study was to investigate the clinical significance and biological function of epidermal growth factor receptor (EGFR) expressed in tumor stroma of epithelial ovarian cancer.MethodsImmunohistological staining of EGFR was evaluated in 242 patients with epithelial ovarian cancer. The correlations of EGFR expression in tumor stroma with clinicopathological features and with the expression level of Ki-67 were analyzed by SPSS software. Kaplan–Meier analysis and the Cox proportional hazard model were used to analyze the effect of EGFR expression in tumor stroma on the prognosis of patients with epithelial ovarian cancer. Meanwhile, the activities of proliferation and migration of tumor cells were detected when EGFR overexpressed in stroma cells.ResultsEGFR expression in tumor stroma correlated significantly with clinical stage (χ2=7.002, P=0.008) and distant metastases (χ2=16.59, P<0.001). Furthermore, there was a significantly positive correlation between the level of EGFR expressed in tumor stroma and the level of Ki-67 expressed in tumor cells (χ2=6.120, P=0.013). Patients with high EGFR expression level in tumor stroma showed poor survival (P=0.002). Multivariate analysis showed that high expression of EGFR in tumor stroma was an independent predictor for epithelial ovarian cancer patients (hazard ratio =1.703; 95% confidence interval 1.125–2.578, P=0.012). Furthermore, stroma cells overexpressing EGFR could promote the proliferation and migration of adjacent tumor cells.ConclusionHigh expression of EGFR in tumor stroma correlates with aggressive clinical features in epithelial ovarian cancer, and is an independent prognostic factor.

Paradigm Shift in the Management Strategy for Epithelial Ovarian Cancer

The hypothesis on the pathogenesis of epithelial ovarian cancer continues to evolve. Although epithelial ovarian cancer had been assumed to arise from the coelomic epithelium of the ovarian surface, it is now becoming clearer that the majority of serous carcinomas arise from epithelium of the distal fallopian tube, whereas clear cell and endometrioid cancers arise from endometriosis. Molecular and genomic characteristics of epithelial ovarian cancer have been extensively investigated. Our understanding of pathogenesis of the various histologic types of ovarian cancer have begun to inform changes to the strategies for management of epithelial ovarian cancer, which represent a paradigm shift not only for treatment but also for prevention, which previously had not been considered achievable. In this article, we will discuss novel attempts at the prevention of high-grade serous ovarian cancer and treatment strategies for two distinct entities in epithelial ovarian cancer: low-grade serous and clear cell ovarian carcinomas, which are relatively rare and resistant to conventional chemotherapy.

D07 - The impact of fasting glucose on clinical-pathological features in epithelial ovarian cancer: results from a historic cohort

D07 - The impact of fasting glucose on clinical-pathological features in epithelial ovarian cancer: results from a historic cohort

Epithelial ovarian cancer with CD117 phenotype is highly aggressive and resistant to chemotherapy.

CD117 expression has a pathogenic role in many malignancies, including ovarian carcinoma. The aim of the present study was to examine the correlation of stemness-associated marker CD117 with the clinicopathologic features of epithelial ovarian cancer and patient survival. The analysis included 240 primary ovarian carcinomas (OC) diagnosed during the period from 2005 to 2011 in the region of South Serbia. Age, pathohistological characteristics, presence and size of residual tumor, choice of therapy and response to the therapy were studied. Residual tumors were more frequently present in the patients with positive CD117 expression (18.1% vs 8.0%; P < 0.05). Chemotherapy according to paclitaxel/carboplatin protocol was more frequent in the patients with positive CD117 expression (70.9% vs 54.2%; P < 0.05), while carboplatin monotherapy was more frequent in the patients with negative CD117 expression (18.0% vs 6.4%; P < 0.05). Median survival time in patients with CD117-positive mucinous and endometrioid OC was significantly shorter, at 20 and 26.8 months, respectively. Median survival in serous OC was not related to CD117 expression. Residual tumors and chemotherapy treatment were more frequent in patients with positive CD117 expression. The outcome was dependent on the type of OC; a worse outcome, including a shorter survival, was documented in the mucinous and endometrioid OC cases.

Plasma immune analytes in patients with epithelial ovarian cancer

ObjectivesInflammation is a common feature of epithelial ovarian cancer (EOC), and measurement of plasma markers of inflammation might identify candidate markers for use in screening or presurgical evaluation of patients with adnexal masses. MethodsPlasma specimens from cohorts of 100 patients with advanced EOC (AJCC Stage III and IV), 50 patients with early stage EOC (Stage I and II), and 50 patients with benign surgical conditions were assayed for concentrations of multiple cytokines, toll-like receptor agonists, and vascular growth factors via ELISA and electrochemiluminescence. Immune proteins were then analyzed for association with EOC. Differences in plasma protein levels between benign, early, and advanced EOC patient groups were assessed with and without adjustment for plasma cancer antigen 125 (CA-125) levels. ResultsOut of 23 proteins tested, six—including interferon gamma (IFNγ), interleukin 6 (IL-6), IL-8, IL-10, tumor necrosis factor alpha (TNFα), and placental growth factor (PlGF)—were univariately associated with EOC (all p<0.005), and one—IL-6—was associated with early stage EOC (p<0.0001). Heat shock protein 90kDa beta member 1 (HSP90B1, gp96) was associated with EOC and early stage EOC with borderline statistical significance (p=0.039 and p=0.026, respectively). However, when adjusted for (CA-125), only HSP90B1 independently predicted EOC (p=0.008), as well as early stage EOC (p=0.014). ConclusionsMultiple plasma cytokines, including IFNγ, IL-6, IL-8, IL-10, TNFα, PlGF, and HSP90B1 are associated with EOC. Of these, HSP90B1 is associated with EOC independent from the biomarker CA-125.

Abstract 3113: Hyperactivation of FOXM1 drives ovarian cancer growth and metastasis independent of the G2-M cell cycle checkpoint.

Abstract Forkhead box M1 (FOXM1) is a TP53- and phosphorylation-dependent transcription factor that plays a critical role in cell cycle progression. Recent analyses by the Cancer Genome Atlas (TCGA) consortium indicate that FOXM1 overexpression may be a key, early event driving the growth of epithelial ovarian cancer (EOC). However, this hypothesis has not been critically tested. Using RT-qPCR, we examined the expression of each of the known FOXM1 splice variants. We found that levels of FOXM1c but not FOXM1b or the translationally inactive FOXM1a are significantly higher in specimens of EOC (n=5) than normal ovary (n=3) or fallopian tube (n=3). By western blot, we found that FOXM1 is highly phosphorylated in EOC, suggesting that its hyperactivation is a consistent feature of ovarian cancer. When FOXM1 expression was targeted in TP53-wt HEYA8, TP53-mutated OVCAR8, and TP53-deficient SkOViP31 ovarian cancer cells by siRNAs, we found that ovarian cancer cell lines with reduced FOXM1 expression grow much more slowly than control cultures transfected with a non-targeting siRNA control and that a loss of FOXM1 results in G2-M cell cycle arrest that can be detected by flow cytometry using propidium iodide stained cells. Reduced FOXM1 expression also inhibited migration and invasion when OVCAR8 and HeyA8 cells were evaluated using standard Boyden chamber assays. Using qPCR and Western blot, we examined the ability of FOXM1 to directly regulate &amp;gt;19 gene products that are highly expressed in EOC. Despite the fact that FOXM1 regulates many of these genes (Cyclin B1, Plk1, and CENPF) in other cells and tissues, levels of their expression were not observed when FOXM1 was knocked down SKOV3ip1, HEY8 and OVCAR8 cells. Therefore, we analyzed patterns of gene expression from 581 TCGA ovarian cancer specimens using serial linear regression with L1 normalization (Lasso analysis) to test for correlations with FOXM1 expression. These analyses identified multiple gene products whose expression is potentially regulated by FOXM1 in ovarian cancer. Altered levels of expression for multiple gene products identified by these analyses have been examined by qPCR and Western blot in ovarian cancer cell lines transfected with shRNA targeting FOXM1 expression. These included multiple gene products, including VEGF-B and -C known to regulate angiogenesis. To explore the in vivo impact of targeting FOXM1 expression, a xenograft model was established by inoculating Fox1Nu mice with OVCAR8 cells stably transfected with either shRNA targeting FOXM1 and a non-targeting control. Collectively, these results indicate that hyperactivation of FOX1-mediated transcriptional activity is a consistent feature of EOC and plays a critical role in regulating ovarian cancer metastasis in addition to proliferation. FOXM1 may be a valuable therapeutic target for overcoming the genetic heterogeneity that limits current ovarian cancer treatments. Citation Format: Triparna Ghosh-Choudhury, Holli A. Loomans, Ying-Wooi Wan, Zhangdon Liu, Shannon M. Hawkins, Matthew L. Anderson. Hyperactivation of FOXM1 drives ovarian cancer growth and metastasis independent of the G2-M cell cycle checkpoint. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3113. doi:10.1158/1538-7445.AM2013-3113

A Detailed Study of Patients and Tumor Characteristics of Epithelial Ovarian Cancer in Saudi Women

The Saudi population is characterized by high parity and intermarriages that may impact ovarian carcinogenesis. Herein, we analyzed the tumor characteristics and outcomes in Saudi patients with epithelial ovarian cancer (EOC). Patients with EOC treated at King Faisal Specialist Hospital and Research Center during 1995-2007 were identified retrospectively through a review of their medical records. Patients' and tumor characteristics were collected including age at diagnosis, marital status, parity, histology, stage, treatment rendered, and follow-up data. One hundred-ninety-three patients with EOC were identified in this cohort. The mean age of the patients was 55 ± 15 years, the mean ± SD body mass index was 27.0 ± 5.6 kg/m, and the median parity was approximately 7.0. Whereas 4 patients reported a family history of cancer, 164 women reported negative family history; and it was unknown in 27 cases. Tumor distribution by International Federation of Gynecology and Obstetrics stage was the following: 12 patients (6.2%) had stage I disease at diagnosis, 1 patient (0.5%) stage II disease, 130 patients (67.4%) stage III disease, 39 patients (20.2%) stage IV disease, and that of 11 patients (5.7%) was unknown. Information on residual disease after surgery was available on 98 patients with optimal debulking (<1 cm) achieved in 61 cases. Median progression-free survival from end of chemotherapy to recurrence/progression was 11.9 months (95% confidence interval, 9.4-15.2). Tumor histology, size of residual disease, and stage at diagnosis were significant prognostic factors. The patients' age, body mass index, tumor histology, and grade had no impact on survival. Patients presenting with advanced-stage disease are higher among Saudis than those reported in global literature. Despite high intermarriage rates, reported family history for related cancers was quite low in this cohort. Notably, this is the first study evaluating EOC in Saudi patients.

EPITHELIAL OVARIAN CANCER;

Background: Epithelial ovarian cancer is the most common cancer of gynaecologic origin in Pakistani women. It ranks amongthe ten most common cancers in our women. Despite being commonly encountered, information regarding the clinicopathological features islacking. Objective: To study the clinical and pathological features of epithelial ovarian cancer in our patients. Study Design: Retrospective study.Setting: Department of Medical Oncology, Jinnah Hospital Lahore. Period: Jan 01,2001 to Dec 31, 2002. Patients and methods: All patientswith histological or cytological diagnosis of epithelial ovarian cancer regardless of stage were included in the study. Information was obtainedfrom medical records which were reviewed thoroughly. Blood samples for analysis of BRCA mutations were sent to University of Toronto,Sunnybrook &amp; Women’s College Health Sciences Centre, Toronto, Canada. Results: 75 patients were accrued. Mean age of the patients was47 years. The well defined risk factors such as nulliparity, lack of lactation, early menarche and late menopause were not present in the majorityof our patients. One striking feature was the number of patients with family history of cancer (18.7%). Majority were first degree relatives of thepatients and most had ovarian or breast cancer. BRCA1 and BRCA2 were seen in nine (12%) of the patients. Clinical presentation and histologicfeatures were similar to American and European patients, the only difference was that a large number (88%) of our patients presented withadvanced (stage III or IV) disease. Conclusions: Epithelial ovarian cancer manifests itself in a younger population of our women. Higherfrequency of positive family history was another striking feature of Pakistani patients.

Polymorphisms in the CASP8 gene and the risk of epithelial ovarian cancer

Objective The CASP8 gene plays a central role in the apoptotic pathway and is therefore a plausible cancer susceptibility gene. However, the precise role of the CASP8 gene in epithelial ovarian cancer carcinogenesis is unclear. Therefore, we analyzed the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in CASP8 and the risk and clinical characteristics of epithelial ovarian cancer (EOC) in the Chinese population. Subjects and methods Eight tag SNPs were identified using the MassARRAY system to genotype 37 genetic polymorphisms around and in the CASP8 gene in 100 unrelated, healthy females. Then, a case-control study of 218 EOC patients and 285 controls who were matched on residence, age and race was conducted using these 8 tag SNPs. Results The risk of developing EOC was significantly decreased in association with CASP8 rs3834129 ins > del (odds ratio (OR) del/del = 0.129, 95% confidence interval (95% CI): 0.038–0.439; OR ins/del = 0.769, 95% CI, 0.534–1.108), rs3769827 T > C (OR C/C = 0.187, 95% CI: 0.070–0.500; OR T/C = 0.729, 95% CI: 0.505–1.052), rs6704688 C > T (OR T/T = 0.344, 95% CI, 0.168–0.707; OR C/T = 0.802, 95% CI, 0.552–1.166), and with the del-C-T haplotype of these 3 SNPs (OR = 0.615, 95% CI: 0.453–0.8363). Moreover, a notably later onset was significantly associated with the rs3834129 ins/del + del/del and the rs3769827 T/C + C/C genotypes (p < 0.0001). Conclusions Genetic variants of the CASP8 gene protect against EOC carcinogenesis and delay the age of EOC onset. Furthermore, these protective effects may be due to the dysfunctional expression of caspase-8 caused by the − 652 6 N del variant in the promoter.

Expression and significance of P53, P21WAF1 and CDK1 proteins in epithelial ovarian cancer

P53, P21WAF1 and CDK1 are key factors in the "P53 pathway" of G2/M phase DNA damage checkpoint in cell cycle. This study was to investigate the expression and significance of P53, P21WAF1 and CDK1 proteins in epithelial ovarian cancer. The expression of P53, P21WAF1 and CDK1 proteins in 20 specimens of normal ovarian tissues, 20 specimens of benign epithelial ovarian tumor and 76 specimens of epithelial ovarian cancer was detected by immunohistochemistry. Their correlations to the clinicopathologic characteristics of epithelial ovarian cancer and their interrelationships were analyzed. Significant differences were noted in the positive rates of P53, P21WAF1 and CDK1 proteins between epithelial ovarian cancer and normal ovarian tissues, benign ovarian tumors (P < 0.05). In epithelial ovarian cancer, up-regulation of P53 protein was associated with advanced FIGO stage and poor differentiation; down-regulation of P21WAF1 protein was associated with advanced FIGO stage; CDK1 showed no association with any clinicopathologic factors. P53 and CDK1 expression were negatively correlated to P21WAF1 expression (r = -0.388, P = 0.001; r = -0.282, P = 0.014); P53 expression was positively correlated to CDK1 expression (r = 0.263, P = 0.022). P53 protein is related to the malignancy of epithelial ovarian cancer, P53 and P21WAF1 protein may be related to the malignant development of epithelial ovarian cancer. CDK1 detection may be helpful in the early diagnosis of epithelial ovarian cancer.

Relative expression levels of Th1 and Th2 cytokine mRNA are independent prognostic factors in patients with ovarian cancer

The aim of the present study was to examine mRNA expression levels of Th1 (TNF-alpha , IFN-gamma, and IL-12p40) and Th2 (IL-6 and IL-10) cytokines for any association with clinicopathological characteristics of epithelial ovarian cancer. mRNA was isolated, and cDNA prepared from 40 samples of epithelial ovarian cancers. Expression level of each cytokine mRNA was examined by the real-time PCR technique (GAPDH gene, internal control). Expression ratio (target gene/GAPDH) was used to evaluate gene expression. Results were analyzed against clinical stage, histological grade, and histological type. Prognostic significance of expression levels of each combination of Th1/Th2 values was assessed. Tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) expression levels were significantly higher in serous adenocarcinoma than in non-serous adenocarcinoma (p<0.05), but with no difference between individual cytokine mRNA expression levels and clinical stage or histological grade. Log-rank testing showed that high TNF-alpha mRNA expression (p=0.033) and the diameter of largest residual lesion at initial surgery (p=0.012) significantly correlate with longer survival in advanced stage (II/III/IV) ovarian carcinomas. In examining all combinations of Th1/Th2 expression values, the most significant association was between high IFN-gamma.IL-12p40/IL-6 expression levels and better prognosis in advanced stage (II/III/IV) ovarian carcinomas (p=0.004). In multivariate analysis, high IFN-gamma.IL-12p40/IL-6 expression (p=0.009) and the diameter of residual lesion (p=0.011) remained significantly associated with survival, whereas high TNF-alpha expression lost significance. In conclusion, Th1 and Th2 cytokines might play an important role in regulating the immune reaction in epithelial ovarian cancer cells. IFN-gamma.IL-12p40/IL-6 expression may be a useful prognostic molecular marker for patients with advanced ovarian cancer.

Oral contraceptives and ovarian cancer.

The protection conveyed by oral contraceptives against ovarian cancer risk is one of the best established and most important features of epithelial ovarian cancer on a public health scale. Ovarian cancer incidence and mortality rates have been declining in most developed countries for women born after 1920, and the decline was greater in countries where oral contraceptive use has been more widespread. Thus, data from descriptive epidemiology are consistent with a favourable effect of oral contraceptives on ovarian cancer risks. The overall estimated protection from cohort and case-control studies is approximately 40% in ever oral contraceptive users, and increases with duration of use to more than 50% for users of 5 years or longer. The favourable effect of oral contraceptives against ovarian cancer risk persists for at least 10-15 years after use has ceased, and it is not confined to any particular type of oral contraceptive formulation. However, available data do not provide definite evidence for more recent low-dose formulations and for longer periods of latency or recency of use. The protection is also observed on borderline malignancy ovarian neoplasms, and probably on benign epithelial cysts as well. There is suggestive evidence of some protection for sex-cord-stromal cancers, but not for germ cell neoplasms. In terms of biological mechanisms, oral contraceptives are thought to act on ovarian cancer risk by affecting the lifetime number of ovulations. The protection attributable to oral contraceptives on ovarian cancer risk is one of the major issues on any individual risk/benefit assessment and public health evaluation of this type of contraceptive use.

CD44 variant expression is a common feature of epithelial ovarian cancer: lack of association with standard prognostic factors.

CD44 is a hyaluronic acid receptor that exists as a standard 90-kd form (CD44S) as well as several CD44 variant isoforms produced through alternative splicing. Expression of CD44 variants is associated with clinically aggressive behavior in some human tumors. The purpose of the present study is to define the expression of CD44 variant isoforms in ovarian cancer and to investigate whether the expression of these molecules is associated with adverse prognosis. Six specimens of normal ovarian surface epithelium (NOSE) and 31 separate cases of newly diagnosed ovarian cancer were studied by a combination of reverse-transcription polymerase chain reaction (RT-PCR) and immunoperoxidase staining. Clinical correlation was made between CD44 variant expression and stage (I/II v III/IV), residual disease (< or = 2.0- v > 2.0-cm mass), age (< or = 65 v > 65 years), histology (papillary serous v other), grade, and survival. RT-PCR analysis revealed that NOSE predominantly expressed transcripts for CD44S, as well as a restricted pattern of transcripts characteristic of CD44 splice variants. CD44S and CD44 variant exon nine sequences (CD44-9v) were focally expressed in one of two NOSE specimens examined by immunoperoxidase staining. In comparison, the majority (71%) of ovarian cancer specimens expressed a complex pattern of CD44 splice variants by RT-PCR analysis. Immunoperoxidase studies revealed that the majority of ovarian cancer specimens expressed both CD44S and CD44-9v, whereas expression of sequences from variant exons 3, 4, and 6 was uncommon. There was no association between CD44 variant expression (transcript or protein) and stage, residual disease, age, histology, grade, or survival. Expression of CD44S and CD44-9v is a common feature of epithelial ovarian cancer cells. The lack of a significant association between CD44 variant expression and prognosis suggests that other factors may be more important in determining the clinical behavior of this disease.