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Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma - PubMed

  • ️Tue Jan 01 2013

. 2013 Sep 1;119(17):3242-50.

doi: 10.1002/cncr.28175. Epub 2013 May 29.

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Differential expression and prognostic value of ERCC1 and thymidylate synthase in resected gastric adenocarcinoma

Malcolm H Squires 3rd et al. Cancer. 2013.

Abstract

Background: Excision repair cross-complementing gene-1 (ERCC1) and thymidylate synthase (TS) are key regulatory enzymes whose expression patterns are associated with overall survival (OS) in several malignancies. Their expression patterns and prognostic value in resected gastric adenocarcinoma (GAC) are not known.

Methods: In total, 109 patients who underwent resection for GAC between January 2000 and June 2011 had tissue available for analysis. The primary objective was to assess for the differential expression of ERCC1 and TS using immunohistochemistry. The secondary objective was to assess for the association between OS and the expression of ERCC1 and TS.

Results: The median follow-up was 21.2 months, and the median OS was 28.8 months. Resected GAC exhibited differential expression of ERCC1 (high expression, 23%; n = 25) and TS (high expression, 43%; n = 47). ERCC1 and TS expression were not associated with OS. In a subset analysis of patients who received chemotherapy (n = 73), high ERCC1 expression was associated with decreased OS (16.7 months vs 53.8 months; P = 0.03). After controlling for known adverse pathologic features, high ERCC1 expression persisted as a negative prognostic factor in multivariate Cox regression analysis (hazard ratio, 2.5; 95% confidence interval, 1.03-6.0; P = .04). Conversely, in patients who underwent resection only (n = 35), high ERCC1 expression demonstrated a trend toward improved OS (40.4 months vs 12.7 months; P = .10); a positive prognostic influence also was present on multivariate analysis (hazard ratio, 0.20; 95% confidence interval, 0.04-0.86; P = .03).

Conclusions: Resected GAC exhibited differential expression of TS and ERCC1. Among all patients, ERCC1 and TS expression levels were not associated with OS. High ERCC1 tumor expression was associated with decreased OS in the patients who received chemotherapy but was associated with increased OS in those who underwent surgery alone. ERCC1 expression had prognostic value in resected gastric cancer, and further investigation is warranted.

Keywords: ERCC1; biomarkers; gastric adenocarcinoma; thymidylate synthase.

Copyright © 2013 American Cancer Society.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES

The authors made no disclosures.

Figures

Figure 1
Figure 1

Tumor expression levels of excision repair cross-complementing gene-1 (ERCC1) and thymidylate synthase (TS) were evaluated using immunohistochemistry. Representative images are depicted (original magnification ×400). (a) Low ERCC1 expression was observed in 84 patients (77%), (b) high ERCC1 expression was observed 25 patients (23%), (c) low TS expression was observed in 61 patients (57%), and (d) high TS expression was observed in 48 patients (43%).

Figure 2
Figure 2

(a) Tumor expression of excision repair cross-complementing gene-1 (ERCC1) and overall survival (OS) are illustrated for all patients (n =108). NS indicates nonsignificant. (b) Tumor thymidylate synthase (TS) expression and OS are illustrated for all patients (n =108).

Figure 3
Figure 3

These Kaplan-Meier survival curves illustrate a subset analysis of tumor excision repair cross-complementing gene-1 (ERCC1) expression and overall survival (OS). Median OS is reported. (a) ERCC1 expression and OS is illustrated for patients who received additional therapy (n =73). (b) ERCC1 expression and OS are illustrated for patients who underwent resection only (n=35).

Figure 4
Figure 4

These Kaplan-Meier survival curves illustrate a subset analysis of overall survival (OS) according to treatment modality for patients who underwent surgery and also received additional therapy versus patients who underwent resection only. (a) OS is illustrated for patients who had high excision repair cross-complementing gene-1 (ERCC1) tumor expression (n =25) according to treatment modality. (b) OS is illustrated for patients who had low ERCC1 tumor expression (n =83) according to treatment modality.

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