In:
Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. e17539-e17539
Abstract:
e17539 Background: Cancer-testis antigens (CTAgs) have previously been shown to be markers of poor prognosis and to be associated with chemoresistance in short interference RNA screens. In contradistinction, we recently reported the CTAg NY-ESO-1 predicted improved responses to neoadjuvant chemotherapy in pathological stage IIIA NSCLC. Despite this, no significant survival benefit was seen in NY-ESO-1 positive (NY-ESO-1+) patients. Given that tissues available for staining in the neoadjuvant setting were limited, we investigated a retrospective cohort of patients who underwent curative surgery for pathological N2 disease. As some of these patients were operated on prior to the broad acceptance of adjuvant chemotherapy (ACT), half did not receive chemotherapy. We investigated NY-ESO-1 as a prognostic and/or predictive marker in these patients. Methods: Formalin fixed paraffin embedded tissues were reviewed and stained using standard methods for a panel of CTAgs including NY-ESO-1 by immunohistochemistry. Tumors were categorized as NY-ESO-1+ or NY-ESO-1-. Isolated DNA was subjected to mutation profiling using Sequenom’s MassArray platform. Molecular markers were correlated with clinicopathological features and survival. Results: NY-ESO-1 stained 26/104 (25%) samples, including 15 cases that received ACT and 11 that did not. NY-ESO-1+ tumors were enriched for squamous cell carcinomas over adenocarcinomas (12/29 vs. 8/57; p = 0.01). They also lacked EGFR mutants and were enriched for KRAS mutants amongst adenocarcinomas relative to NY-ESO-1- tumors (5/8 vs. 9/49; p=0.02). NY-ESO-1+ patients who did not receive ACT had significantly worse outcome than NY-ESO-1- patients who did not receive ACT (HR 2.66 1.2-5.86, p=0.01). Median survival favored NY-ESO-1+ patients who received chemotherapy (37.7 months) compared to NY-ESO-1- patients regardless of chemotherapy (28.2 ACT vs 15.7 No ACT; p= 0.25) and NY-ESO-1+ patients who did not receive ACT (7.75). Conclusions: In this dataset, NY-ESO-1 was poorly prognostic but also predictive for more favorable outcomes with chemotherapy. These data support our previous observation of increased responses to chemotherapy in NY-ESO-1+ N2 patients and warrant further study.
Type of Medium:
Online Resource
ISSN:
0732-183X
,
1527-7755
DOI:
10.1200/jco.2012.30.15_suppl.e17539
Language:
English
Publisher:
American Society of Clinical Oncology (ASCO)
Publication Date:
2012
detail.hit.zdb_id:
2005181-5
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