GNTA related abstract from ASCO
Evaluation of Bcl-2 expression in melanoma - A tissue microarray study. Abstract No: 7515
Author(s): K. A. Divito, M. Dolled-Filhart, R. Camp, A. Berger, D. Rimm, H. Kluger; Yale University, New Haven, CT
Abstract: Background: Metastatic melanoma remains a highly chemotherapy-resistant disease, for which there is no cure. One of the few recent advances in treating metastatic melanoma is the addition of Bcl-2 antisense to dacarbazine as first line therapy, which increases response rates, median survival and disease free survival. Studies in the literature report a very wide range of frequencies of expression of the anti-apoptotic protein Bcl-2 in melanoma specimens (60% to 96%). Some reports have shown up regulation of Bcl-2 with increased disease aggression, while other groups have demonstrated an inverse relationship. These studies have included fewer than 100 patients; therefore we sought to re-address this issue using a large cohort of melanoma specimens. Methods: Tissue microarrays containing specimens from 282 melanoma patients with 20 year follow-up were employed and evaluated with our AQUA system for automated quantitative analysis. The system uses S100 to define pixels as melanoma (tumor mask) within the array spot, and then measures intensity of Bcl-2 expression using Cy5 conjugated antibodies within the mask. Scores were divided into quartiles, and correlated with clinical and pathological variables.*** Results: High Bcl-2 expression was associated with better outcome in the entire cohort and among the metastatic specimens only (P = 0.02 and P = 0.01, respectively)***. Bcl-2 expression was higher in primary than in metastatic specimens (P = 0.002) and in patients older than 50 years of age (P = 0.03). Among the primary specimens there was no association between Bcl-2 expression and Breslow depth and Clark level. Conclusions: High Bcl-2 expression is associated with better survival in melanoma and with earlier stage disease. The diverse results in the literature might be due to use of small cohorts or to variability in staining technique. Studies are needed to evaluate the association between Bcl-2 expression and response to Bcl-2 antisense. Patient selection based on Bcl-2 expression might improve response rates to Bcl-2 antisense.
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I am not sure what "High Bcl-2 expression was associated
with better outcome in the entire cohort and among the
metastatic specimens only" means.
But it does seem somewhat hopeful that a subset of melanoma
patients might be treated by GNTA's drug.
Norman |
