High Expression of Folate Receptor Alpha in Lung Cancer Correlates with Adenocarcinoma Histology and EGFR Mutation.
Maria I Nunez, Carmen Behrens, Denise M Woods, Heather Lin, Milind Suraokar, Humam Kadara, John D Minna, Wayne Hofstetter, Neda Kalhor, Wong K Hong, Jack J Lee, Wilbur Franklin, David Stewart, Ignacio I Wistuba. MD Anderson Cancer Center, Houston, TX; The University of Texas Southwestern Medical Center, Dallas; University of Colorado, Denver
Background: Folate receptor alpha (FRa) and receptor folate carrier-1 (RFC1) regulate cellular uptake of folate molecules inside the cell, and are potential biomarkers of tumor response to antifolate chemotherapy. Information on the protein expression of these receptors in non−small cell lung carcinoma (NSCLC) is limited.
Design: Expressions of FRa and RFC1 were examined by IHC in 320 surgically resected NSCLC (202 ADC and 118 SCC) tissue specimens using TMA. The findings were correlated with patient clinicopathologic characteristics. To address FRa expression level with tumor progression, analysis of specimens from advanced tumors and brain metastasis was performed. FOLR1 mRNA expression was examined using publicly available microarray datasets. FRa expression was correlated with tumors' thymidylate synthase (TS) in NSCLCs, and with EGFR and KRAS mutations in ADC.
Results: NSCLC frequently over expressed both FRa and RFC1 in samples from early and advanced stages of the disease. In a multivariate analysis, lung ADC were more likely to express FRa in the cytoplasm (odds ratio [OR] = 4.39; P<0.0001) and membrane (OR = 5.34; P<0.0001) than SCC. Tumors from never-smokers were significantly more likely to express cytoplasmic (OR = 3.35; P<0.03) and membrane (OR = 3.60; P=0.0005) FRa than those from smokers. FRa and RFC1 expressions did not correlate with NSCLC patients' outcome. In ADC, EGFR mutations correlated with higher expression of membrane FRa and FOLR1 gene expressions. FRa and TS expression inversely and significantly correlated (P=0.03).
Conclusions: Membrane transporter FRa and RFC1 proteins are frequently over expressed in NSCLC tissues at all tumor stages. The higher levels of FRa correlate with lung ADC histotype and presence of EGFR mutation.
This study was supported in part by grants from the DO (W81XWH-07-1-0306 to J.D.M., W.K.H., D.J.S., and I.I.W.), the SPORE (P50CA70907 to J.D.M. and I.I.W.), and the NCI (Cancer Center Support Grant CA-16672).
Tuesday, March 1, 2011 1:00 PM
Poster Session IV # 264, Tuesday Afternoon