Overexpression of the Six1 Homeobox Gene Is Associated with Diffuse Peritoneal Spread and Larger Residual Disease after Maximal Cytoreductive Effort in Advanced Ovarian Cancer

Abstract

Study Design: Between January 2003 and June 2009, we collected fresh tumor and extracted high-quality RNA from the omental/peritoneal metastases of 47 patients with stage IIB-IV ovarian cancer. Clinical data were abstracted from the patients’ medical records. Expression of Six1 level by quantitative RT-PCR was compared with preoperative factors and intraoperative findings using the χ 2 test and the Fisher exact test. The effect of Six1 elevation on survival was assessed with the Kaplan/Meier method. Results: The mean age of patients enrolled was 60 (range 33 - 84). The histological subtypes were 77% serous (36/47), 11% endometrioid (5/47), 4% mucinous (2/47), and 4% clear cell (2/47). Eighty-one percent were optimally cytoreduced. Median Six1 expression for the samples was 114 fg/ng 18S rRNA and Six1 overexpression, defined as >300 fg/ng 18S rRNA, was observed in 19% of tumors. Six1 expression above sample median was associated with peritoneal disease (p = 0.049) and inability to optimally cytoreduce (p = 0.02). Six1 overexpression was associated with worsened survival in the high grade serous subgroup (43 months versus 71 months, p = 0.039 Log Rank test). Conclusions: Elevated levels of Six1 predict peritoneal disease and larger residual tumor after maximal cytoreductive effort. Prospective prediction of surgical cytoreduction using a combination of Six1 expression, included with other factors, is currently being evaluated.