Positive PTEN Expression Is Associated with Decreased Survival in Ovarian/Primary Peritoneal High Grade Serous Carcinoma.
Rania Bakkar, Diana Urbauer, Russell Broaddus. MD Anderson Cancer Center, Houston, TX
Background: Ovarian/peritoneal high grade serous carcinoma typically presents at advanced stage and has a low 5 year survival rate. Optimal surgical debulking and tumor sensitivity to platinum-based chemotherapy are two well-established prognostics. Molecular markers that identify more clinically aggressive tumors would allow for the development of individualized treatment options. PTEN is a key negative regulator of the PI3K signaling pathway. Loss of PTEN expression in endometrial carcinoma is associated with endometrioid histology; women with endometrioid tumors have a better prognosis than those with non-endometrioid tumors. In breast cancer, loss of PTEN is associated with resistance to Herceptin. Thus, measurement of PTEN expression has the potential to provide important prognostic information. Currently, there is no established clinical scoring system for assessing PTEN expression by immunohistochemistry (IHC). Therefore, we first established a useful PTEN IHC scoring system and then determined if PTEN expression was associated with relevant clinical variables in ovarian high grade serous carcinoma.
Design: PTEN IHC (Dako, clone 6H2.1) was assessed in 126 women with stage III, high-grade serous carcinoma of the ovary/peritoneum who were treated with surgery and then a platinum plus taxane regimen. A 3-tiered scoring system was developed (negative, reduced, positive) based on tumor expression of PTEN in relation to stroma, which was always strongly positive. Immunohistochemistry for anti-phosphorylated (serine 235/236) S6 ribosomal protein (pS6) was performed to validate the PTEN scoring system. PTEN expression was assessed in relation to clinical characteristics using Cochran-Armitage trend test, Fischer's exact test and log-rank trend test.
Results: 11% of the cases had complete loss of PTEN by IHC. The presence of significantly increased pS6 expression in these cases helped to validate the PTEN IHC scoring system. PTEN protein expression was not associated with platinum resistance or surgical debulking status. Positive PTEN expression, which was present in 58% of the cases, was significantly associated with decreased recurrence free survival compared to tumors with negative or reduced PTEN expression (18 months vs. 29 months; p=0.0009).
Conclusions: We have developed a clinically useful scoring system for PTEN IHC in ovarian cancer which can be used for assessing patient eligibility for treatment with PI3K inhibitors. Importantly, positive PTEN expression is associated with decreased survival. This may help to identify patients who can receive more aggressive therapy.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 140, Monday Morning