Increased ERCC Expression Correlates with Improved Outcome of Patients Treated with Cisplatin as an Adjuvant Therapy for Curatively Resected Gastric Cancer

Abstract

Purpose: It has been reported that the overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is essential for the repair of cisplatin (CDDP)-DNA adducts, negatively influences the effectiveness of CDDP-based therapy for primary gastric cancer. W e investigated whether the ERCC1 expression was associated with survival for gastric cancer patients in an adjuvant setting.M aterials and Methods: W e retrospectively analyzed 44 patients who were diagnosed with stage II or higher disease after undergoing curative resection and they had also received cisplatin-based chemotherapy. The

ERCC1 protein, mRNA expression and T19007C polymorphism as prognostic markers in head and neck squamous cell carcinoma patients treated with surgery and adjuvant cisplatin-based chemoradiation

“…This interpretation, as commented by Gazdar (15), is compatible with the results of a large biomarker study in non-small cell lung cancer (10). Increased ERCC1 expression was also shown to be correlated with improved outcome of patients treated with cisplatin as an adjuvant therapy for curatively resected gastric cancer (31). The clinical scenario of the latter study is analogous to ours, an aggressive tumor primarily treated by surgery, with a modest benefit for adjuvant therapy.…”

Biomarker analysis in stage III–IV (M0) gastric cancer patients who received curative surgery followed by adjuvant 5-fluorouracil and cisplatin chemotherapy: epidermal growth factor receptor (EGFR) associated with favourable survival

“…The degree of ERCC1 protein expression was found to be inversely associated with this response, which is potentially relevant to clinical resistance to platinum compounds (Kwon et al, 2007). In patients with curatively resected gastric cancer, it was shown that increased ERCC1 expression was correlated with improved outcome (Baek et al, 2006). In patients with completely resected non-small-cell lung cancer, ERCC1-negative tumours showed greater benefit from cisplatin-based adjuvant chemotherapy compared with ERCC1-positive tumours (Olaussen et al, 2006).…”

Association of Four ERCC1 and ERCC2 SNPs with Survival of Bone Tumour Patients

“…It is implied the High ERCC1 and ERCC2 levels are related to increased removal of cisplatin -induced DNA adducts and cisplatin resistance. Previous experimental and epidemiological studies showed the ERCC1 118C allele and ERCC2 751G allele are associated with higher mRNA levels and DNA singlestrand break repair than ERCC1 118T allele and ERCC2 751A allele genotypes, and thus to induce the resistance to cisplatin-based chemotherapy which used to damage the DNA of cancer cells, and the polymorphisms in ERCC1 118T allele and ERCC2 751A allele are associated with decreased risk of death from several cancers, such as non-small-cell lung cancer, gastric cancer, nasopharyngeal cancer, and breast cancer (Baek et al, 2006;Rajaraman et al, 2008;Cao et al, 2011;Sun et al, 2011). Only one previous study reported the ERCC2 751G allele are associated with response to cisplatin chemotherapy and shorter event-free survival in osteosarcoma patients (Caronia et al, 2009).…”

“…SNPs in the ERCC1 and ERCC2 genes have been found to be associated with the platinum response in different clinical studies. In particular, the polymorphisms of ERCC1 and ERCC2 were reported to be associated with increased survival and better prognosis in several cancer, such as non-small-cell lung cancer, colorectal cancer, gastric cancer, nasopharyngeal cancer, bladder cancer, and breast cancer (Baek et al, 2006;Rajaraman et al, 2008;Cao et al, 2011;Ishibashi et al, 2011;Sun et al, 2011;Rouissi et al, 2011). Few studies clarified the association of SNPs in ERCC1 and ERCC2 with bone tumor.…”