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. Cancer 2006. © 2006 American Cancer Society.