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Gastrin-releasing peptide receptor expression in Brazilian and Japanese patients with lung cancer and normal lung tissue samples from healthy individuals.

10588 Background: Gastrin-releasing peptide receptors (GRPR) are over-expressed in several neoplasms and can play a critical role in tumor cell survival in preclinical models. A Phase I trial of RC-3095, a synthetic GRPR antagonist, conducted by our group, showed antitumor activity but no significant dose-limiting toxicities. For the development of Phase II clinical trials program of RC-3095, candidate tumor types are being selected on basis of GRPR expression. Data on GRPR expression in lung cancer is limited.


METHODS
We analyzed the expression of GRPR receptors in tumor samples obtained from patients (pts) with lung cancer from a Brazilian (n=238) and a Japanese cohort (n=96), as well as from a control group of individuals with normal lung tissue (n=23). Standard immunohistochemistry (IHC) technique was used. Our aim was: (1) to determine GRPR expression in non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC); (2) to correlate its expression with clinical stages and demographic variables; (3) to compare GRPR expression in Asian and non-Asian population.


RESULTS
In a control group of normal lung tissue samples, GRPR expression was absent or very low as compared to tumor samples (p=0.049). GRPR expression was higher in NSCLC as compared to SCLC (48% weak; 16% moderate; 7.5% strong IHC intensity versus 34% weak; 16% moderate; 3% strong ICH intensity, respectively; p=0.3). Strong GRPR expression was more pronounced in patients at advanced stages (III and IV) vs. samples from patients presenting at earlier clinical stages (p=0.01). GRPR expression was more prevalent in Japanese pts. vs. the Brazilian pts. (93% vs. 62%, respectively; p= 0.001).


CONCLUSIONS
This is the first study to demonstrate that significant levels of GRPR expression can be found in both NSCLC and SCLC. As it was previously shown for EGFR expression, GRPR expression also differs among Asian and non-Asian lung cancer pts. On the basis of these results, pts. with advanced lung cancer, whose tumors exhibit a moderate/high GRPR expression, will be considered candidates for our Phase II trials, regardless of the histological classification.