Journal of Clinical Oncology, 2005 ASCO Annual Meeting Proceedings.
Vol 23, No 16S (June 1 Supplement), 2005: 9683
© 2005 American Society of Clinical Oncology

This Article Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rashid, A. Articles by Varadhachary, G. R. Search for Related Content PubMed Articles by Rashid, A. Articles by Varadhachary, G. R.

Abstract

Overexpression and prevalence of molecular markers in patients with cancer of unknown primary (CUP)

M.D. Anderson Cancer Ctr, Houston, TX

9683

Background: Despite extensive research on molecular markers in cancer, little is known about markers in CUP, which may be biologically distinct from other metastases. We retrospectively evaluated overexpression of 5 molecular markers in CUP. Methods: We examined 100 serial paraffin blocks from UPC pts with biopsies or resections done at UTMDACC. 76 with adequate tissue, were stained by immunohistochemistry for EGFR, VEGF-A, COX-2, c-erbB2, and c-kit. The staining intensity was graded on a four-tier scale from 0 to +3. We could estimate the proportion of marker overexpression with a margin of error (half-width of 95% CI) < 0.10. Results: Majority (75%) of tumors stained for EGFR and 49% for VEGF. 2+ or 3+ staining intensity was present in 61% of tumors for EGFR and 24% for c-erbB2. EGFR was frequently present with other marker(s), seen along with VEGF, c-erbB2 or Cox-2 in at least 30% of the pts. Out of the 10 possible triple staining combinations, only 3 were observed: EGFR/c-erbB2/VEGF (29%), EGFR/c-erbB2/Cox-2 (25%), and c-erbB2/Cox-2/VEGF (18%). Kaplan Meier survival by intensity of staining (0–3) did not show any significant trend. Putting 4 markers into a recursive partitioning analysis identified 5 groups based on expression values for EGFR, c-erbB2 and Cox2. Group 1 was all the EGFR (-) pts; group 2 was pts with EGFR expression, but not c-erbB2; group 3 pts were EGFR > 0, c-erbB2 =1+; group 4 pts were EGFR > 0, c-erbB2 > 1+ but with (-) Cox2; and group 5 pts were EGFR > 0, c-erbB2 > 1+, and Cox2 > 0. Median survival for grps 1, 2 and 4 combined (N = 44) was 12 mo. compared to 28 mo. for grps 3 +5 (N = 30) (p = 0.0079). Analysis with a Cox regression model did not yield significant survival prediction. Conclusions: This study describes expression of molecular markers in CUP. We observed interesting co-expression of markers, which may guide selection of combination targeted therapies in trials. The early indication of survival benefit in c-erbB2+ pts should be evaluated prospectively.

View larger version (6K): [in this window] [in a new window]