Khuri F R, Lotan R, Kemp B L, Lippman S M, Wu H, Feng L, Lee J J, Cooksley C S, Parr B, Chang E, Walsh G L, Lee J S, Hong W K, Xu X C
Departments of Thoracic/Head and Neck Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
J Clin Oncol. 2000 Aug;18(15):2798-804. doi: 10.1200/JCO.2000.18.15.2798.
Retinoids are pivotal in the growth and differentiation of certain epithelial tissues, interacting with nuclear retinoid receptors (the retinoic acid receptors [RARs] and retinoid X receptors [RXRs]), which function as transcription factors. RAR-beta mRNA is undetectable by in situ hybridization (ISH) in 50% of non-small-cell lung cancers (NSCLC). RAR-beta may suppress tumorigenicity. Therefore, we hypothesized that loss of expression of RAR-beta gene in stage I NSCLC is a prognostic factor of a poor clinical outcome.
We retrospectively analyzed RAR-beta mRNA levels (by ISH using a digoxigenin-labeled antisense riboprobe) in specimens from 185 consecutive patients with completely resected clinical/radiographic stage I NSCLC for whom clinical follow-up data were available.
One hundred fifty-six patients who met the criteria of pathologic stage I NSCLC and positivity for RXR-alpha mRNA (used as a control to assess RNA degradation) and who had adequate follow-up could be evaluated. RAR-beta mRNA expression was undetectable in 51 patients, weakly positive in 64 patients, and strongly positive in 41 patients. Overall survival of the 41 patients with strongly positive RAR-beta was significantly worse than for the 115 patients with weak or absent RAR-beta (P =.045).
Unexpectedly, strong RAR-beta expression was associated with a significantly worse outcome of early-stage NSCLC. The mechanisms underlying this clinically and biologically important finding should be further explored.
