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

Abstract

BACKGROUND:

Lysophosphatidic acid acyltransferase-beta (LPAAT-beta) tumor expression is an emerging prognostic, diagnostic, and therapeutic target in early epithelial ovarian cancer (EOC). The significance of tumor overexpression of LPAAT-beta was investigated in a large number of advanced- and early-stage EOC patients.

METHODS:

LPAAT-beta 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-beta in local tumor and distant metastases.

RESULTS:

LPAAT-beta was overexpressed in 90 (57%) of all 158 ovarian tumors. Forty-nine (72%) of 68 advanced tumors overexpressed LPAAT-beta. LPAAT-beta 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-beta increased with but was not significantly associated with advanced clinical stage (P = .1431). LPAAT-beta expression was associated with shortened progression-free survival (PFS) (5-year PFS, 32% for LPAAT-beta-positive vs. 60% for LPAAT-beta-negative; P = .0318) and decreased overall survival (OS) (5-year OS, 54% for LPAAT-beta-positive vs. 74% for LPAAT-beta-negative; P = .0173).

CONCLUSIONS:

LPAAT-beta is highly expressed in advanced ovarian tumors and is associated with aggressive histology and decreased PFS and OS. LPAAT-beta is an intriguing prognostic tool for the identification of high-risk EOC and a potential target for directed therapy that warrants further study.

• Authors: Catherine S M Diefenbach, Robert A Soslow, Alexia Iasonos, Irina Linkov, Cyrus Hedvat, Lynn Bonham, Jack Singer, Richard R Barakat, Carol Aghajanian, Jakob Dupont
• Journal: Cancer (Cancer) Vol. 107 Issue 7 Pg. 1511-9 (Oct 01 2006) ISSN: 0008-543X [Print] United States
• PMID: 16944535 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2006 American Cancer Society.

Chemical References

• Acyltransferases
• 2-acylglycerophosphate acyltransferase

Topics

• Acyltransferases (analysis)
• Adolescent
• Adult
• Child
• Child, Preschool
• Female
• Humans
• Infant
• Neoplasm Metastasis
• Neoplasm Staging
• Ovarian Neoplasms (diagnosis, mortality, pathology)
• Ovary (enzymology, pathology)
• Survival Analysis