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

Sara De Dosso, Elena Zanellato, Martina Nucifora, Renzo Boldorini, Angelica Sonzogni, Roberto Biffi, Nicola Fazio, Eraldo Bucci, Ottavio Beretta, Stefano Crippa, Piercarlo Saletti, Milo Frattini

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)159-165
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume72
Issue number1
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Chemotherapy
DNA Repair
Cisplatin
Stomach Neoplasms
Repair
Genes
Thymidylate Synthase
Drug Therapy
Tumors
Immunohistochemistry
Formaldehyde
Mutation
Adjuvant Chemotherapy
DNA Damage
Disease-Free Survival
Neoplasms
DNA
Survival

Keywords

  • Adjuvant
  • Cisplatin
  • ERCC1
  • Gastric

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Pharmacology
  • Pharmacology (medical)
  • Toxicology

Cite this

ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy. / De Dosso, Sara; Zanellato, Elena; Nucifora, Martina; Boldorini, Renzo; Sonzogni, Angelica; Biffi, Roberto; Fazio, Nicola; Bucci, Eraldo; Beretta, Ottavio; Crippa, Stefano; Saletti, Piercarlo; Frattini, Milo.

In: Cancer Chemotherapy and Pharmacology, Vol. 72, No. 1, 07.2013, p. 159-165.

Research output: Contribution to journalArticle

De Dosso, Sara ; Zanellato, Elena ; Nucifora, Martina ; Boldorini, Renzo ; Sonzogni, Angelica ; Biffi, Roberto ; Fazio, Nicola ; Bucci, Eraldo ; Beretta, Ottavio ; Crippa, Stefano ; Saletti, Piercarlo ; Frattini, Milo. / ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy. In: Cancer Chemotherapy and Pharmacology. 2013 ; Vol. 72, No. 1. pp. 159-165.
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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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T1 - ERCC1 predicts outcome in patients with gastric cancer treated with adjuvant cisplatin-based chemotherapy

AU - De Dosso, Sara

AU - Zanellato, Elena

AU - Nucifora, Martina

AU - Boldorini, Renzo

AU - Sonzogni, Angelica

AU - Biffi, Roberto

AU - Fazio, Nicola

AU - Bucci, Eraldo

AU - Beretta, Ottavio

AU - Crippa, Stefano

AU - Saletti, Piercarlo

AU - Frattini, Milo

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N2 - 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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