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ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy

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Abstract

Background

Adjuvant chemotherapy is gaining an increasing role in resectable gastric cancer. Customizing chemotherapy on the basis of chemosensitivity may improve outcome, and putative predictive molecular markers have been mostly evaluated in Asian patients. We profiled key DNA and damage signaling factors and correlated them with outcome, in a European cohort.

Methods

Formalin-fixed tumor samples obtained from surgical specimens of patients treated with adjuvant cisplatin-based chemotherapy for gastric cancer were analyzed. Immunohistochemistry (IHC) was performed to analyze excision repair cross-complementing gene 1 (ERCC1) and thymidylate synthase (TS) expression, and p53 mutations were detected with direct sequencing.

Results

Among the 68 patient recruited, the median age was 69 (range 30–74), and UICC stage was III in 44 patients (65 %). With a median follow-up of 40.5 months, disease-free and overall survival were 18.0 (95 % CI 13.4–22.76) and 56 months (95 % CI 44.87–67.13), respectively. ERCC1 score was 0 in 14 out 67 (21 %) cases, 1 in 19 (28 %), 2 in 20 (30 %) and 3 in 14 cases (21 %). Longer overall survival (p = 0.04) was found in patients categorized as ERCC1 negative by IHC according to median score. TS score was 0 in 16 out 67 (24 %) cases, 1 in 27 (40 %), 2 in 16 (24 %) and 3 in 8 cases (12 %). Mutations of p53 were found in 21 out 66 (32 %) cases. Neither TS nor p53 were found to correlate with outcome.

Conclusion

Excision repair cross-complementing gene 1 by IHC might predict patients more likely to benefit from adjuvant cisplatin-based chemotherapy in curatively resected gastric cancer. In patients exhibiting ERCC1 positive tumors, alternative regimens should be evaluated.

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Acknowledgments

The work was supported by Fondo di Ricerca Ente Ospedaliero Cantonale.

Conflict of interest

All the authors have no disclosures to declare.

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Authors and Affiliations

  1. Oncology Institute of Southern Switzerland, 6500, Bellinzona, Switzerland

    Sara De Dosso & Piercarlo Saletti

  2. Institute of Pathology, Locarno, Switzerland

    Elena Zanellato, Martina Nucifora, Ottavio Beretta, Stefano Crippa & Milo Frattini

  3. Pathology Institute, University of Piemonte Orientale, Novara, Italy

    Renzo Boldorini

  4. European Institute of Oncology, Milan, Italy

    Angelica Sonzogni, Roberto Biffi & Nicola Fazio

  5. Istituto Ospedaliero MultiMedica, Castellanza, Italy

    Eraldo Bucci

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  1. Sara De Dosso
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Correspondence to Sara De Dosso.

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Piercarlo Saletti and Milo Frattini are senior co-authors.

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De Dosso, S., Zanellato, E., Nucifora, M. et al. ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy. Cancer Chemother Pharmacol 72, 159–165 (2013). https://doi.org/10.1007/s00280-013-2181-2

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