Purpose: Heparan sulfate proteoglycans have been implicated in cancer cell growth, invasion, metastasis, and angiogenesis. This study was designed to compare their expression in normal ovary and ovarian tumors and then to examine their prognostic significance in ovarian cancer.Experimental Design: The expression of syndecan-1, -2, -3, and -4, glypican-1, and perlecan was assessed by immunohistochemistry in 147 biopsies that included normal ovary and benign, borderline, and malignant ovarian tumors. Clinical data, including tumor stage, performance status, treatment, and survival, were collected. Univariate and multivariate analyses were performed to evaluate prognostic significance.Results: The expression patterns of syndecan-1 and perlecan were altered in ovarian tumors compared with normal ovary. Syndecan-1 was not detected in normal ovary but was present in the epithelial and stromal cells of benign and borderline tumors and in ovarian adenocarcinomas. Perlecan expression was decreased in basement membranes that were disrupted by cancer cells but maintained in the basement membranes of blood vessels. Syndecan-2, -3, and -4, and glypican-1 were expressed in normal ovary and benign and malignant ovarian tumors. Stromal expression of syndecan-1 and glypican-1 were poor prognostic factors for survival in univariate analysis.Conclusion: We report for the first time distinct patterns of expression of cell surface and extracellular matrix heparan sulfate proteoglycans in normal ovary compared with ovarian tumors. These data reinforce the role of the tumor stroma in ovarian adenocarcinoma and suggest that stromal induction of syndecan-1 contributes to the pathogenesis of this malignancy.

We report our experience in the management of patients with carcinosarcoma of the ovary, a rare but aggressive variant of ovarian cancer. Forty patients were treated at a single centre, which is the largest reported series. The median age at diagnosis was 65 years (range 45-86) and the median Karnofsky performance (KP) status was 70. Thirty-two patients (80%) presented with FIGO stage III or IV disease. Twenty-four had heterologous and 14 homologous carcinosarcoma on review of histopathology, but there was no significant difference in survival between these groups (P=0.28). Twenty-seven of the 40 patients had bulk residual disease present after surgery and this was associated with a worse prognosis (P=0.045). Chemotherapy was given to 32 patients (80%) of whom 26 (81%) received platinum-based regimens. Of these 32 patients, three (9.4%) achieved a complete response (CR), 10 (31%) a partial response (PR), five (16%) had stable disease, 10 (31%) had progressive disease and four were not assessable. Of the 19 patients who had a CR, PR or stable disease after chemotherapy or were unevaluable (stage Ic), the median survival was 29.6 months. Currently, seven patients are still alive although one has cancer. The overall censored median survival was 8.7 months after a median follow-up of 34 months, and the 1- and 5-year survival were 40 and 7.5%, respectively.

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Purpose Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin,an insulin sensitizer, reduces endometrial tumor growth in vitro. Presurgical window studies allow rapid in vivo assessment of antitumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin in vivo using a robust window study design. Patients and Methods A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850 mg daily for 3 days, and twice daily thereafter) or placebo for 1 to 5 weeks until surgery. The primary outcome was posttreatment IHC expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K–Akt–mTOR and insulin signaling pathways and obesity. Results Eighty-eight women received metformin (n = 45) or placebo (n = 43) and completed treatment. There was no overall difference in posttreatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference −0.57%; 95% CI, −7.57%–6.42%; P = 0.87). Metformin did not affect expression of markers of the PI3K–Akt–mTOR or insulin signaling pathways, and did not result in weight loss. Conclusions Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.