Dr. Bonham was employed by Cell Therapeutics, Inc. (Seattle, WA) when the research was conducted, and is now employed by Amgen, Inc. (Seatle, WA).
Lysophosphatidic acid acyltransferase-β (LPAAT-β) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival
Article first published online: 30 AUG 2006
Copyright © 2006 American Cancer Society
Volume 107, Issue 7, pages 1511–1519, 1 October 2006
How to Cite
Diefenbach, C. S.M., Soslow, R. A., Iasonos, A., Linkov, I., Hedvat, C., Bonham, L., Singer, J., Barakat, R. R., Aghajanian, C. and Dupont, J. (2006), Lysophosphatidic acid acyltransferase-β (LPAAT-β) is highly expressed in advanced ovarian cancer and is associated with aggressive histology and poor survival. Cancer, 107: 1511–1519. doi: 10.1002/cncr.22184
- Issue published online: 18 SEP 2006
- Article first published online: 30 AUG 2006
- Manuscript Accepted: 19 JUN 2006
- Manuscript Revised: 25 MAY 2006
- Manuscript Received: 24 FEB 2006
- NIH Grant. Grant Number: CA-59350
- ASCO Career Development Award 2003
- Damon Runyon-Lilly Clinical Investigator Award
- lysophosphatidic acid acyltransferase-β (LPAAT-β);
- ovarian cancer;
- novel target
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.
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.
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).
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.