Purpose: Retinoids are pivotal in the growth and differentiation of certain
epithelial tissues, interacting with nuclear retinoid receptors (the retin
oic acid receptors [RARs] and retinoid X receptors [RXRs]), which function
as transcription factors. RAR-beta mRNA is undetectable by in situ hybridiz
ation (ISH) in 50% of non-small-cell lung cancers (NSCLC). RAR-beta may sup
press tumorigenicity. Therefore, we hypothesized that loss of expression of
RAR-beta gene in stage I NSCLC is a prognostic factor of a poor clinical o
utcome.
Patients and Methods: 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.
Results: 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 asses
s RNA degradation) and who had adequate follow-vp could be evaluated. RAR-b
eta 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 war significantly worse than for t
he 115 patients with weak or absent RAR-beta (P = .045).
Conclusion: 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 explo
red, J Clin Oncol 18:2798-2804. (C) 2000 by American Society of Clinical On
cology.