Lysophosphatidic acid acyltransferase-β (LPAAT-β) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival

Abstract

BACKGROUND. Lysophosphatidic acid acyltransferase-β (LPAAT-β) tumor expression is an emerging prognostic, diagnostic, and therapeutic target in early epithelial ovarian cancer (EOC). The significance of tumor overexpression of LPAAT-β was investigated in a large number of advanced- and early-stage EOC patients. METHODS. LPAAT-β expression was analyzed by immunohistochemistry (IHC) in 158 ovarian tumors, including 68 advanced and 90 low-stage tumors, representing all grades and histologies (including 33 borderline tumors). In advanced-stage patients, tissue from multiple sites was evaluated to assess differential expression of LPAAT-β in local tumor and distant metastases. RESULTS. LPAAT-β was overexpressed in 90 (57%) of all 158 ovarian tumors. Forty-nine (72%) of 68 advanced tumors overexpressed LPAAT-β. LPAAT-β was associated with the presence of carcinoma versus borderline histology (67% vs. 18%, P < .0001), high histologic grade [according to the Silverberg Grading Scheme] (Grade 1, 25%; Grade 2, 21%; and Grade 3, 54%; P < .0001), and with papillary-serous histology. In an analysis of the 125 carcinoma patients, LPAAT-β increased with but was not significantly associated with advanced clinical stage (P = .1431). LPAAT-β expression was associated with shortened progression-free survival (PFS) (5-year PFS, 32% for LPAAT-β-positive vs. 60% for LPAAT-β-negative; P = .0318) and decreased overall survival (OS) (5-year OS, 54% for LPAAT-β-positive vs. 74% for LPAAT-β-negative; P = .0173). CONCLUSIONS. LPAAT-β is highly expressed in advanced ovarian tumors and is associated with aggressive histology and decreased PFS and OS. LPAAT-β is an intriguing prognostic tool for the identification of high-risk EOC and a potential target for directed therapy that warrants further study. © 2006 American Cancer Society.