Expression of ERCC1, MSH2 and PARP1 in non-small cell lung cancer and prognostic value in patients treated with platinum-based chemotherapy.

Ke-Jie Xie,Hong-Er He,Ai-Jing Sun,Xi-Bo Liu,Xue-Jun Dong,Li-Ping Sun

doi:10.7314/apjcp.2014.15.6.2591

Ke-Jie Xie, Hong-Er He + Show 4 more

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https://doi.org/10.7314/apjcp.2014.15.6.2591

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Abstract

To evaluate the prognostic value of the expression of excision repair cross-complementation group l (ERCC1), MutS protein homolog 2 (MSH2) and poly ADP-ribose polymerase 1 (PARP1) in non-small-cell lung cancer patients receiving platinum-based postoperative adjuvant chemotherapy. Immunohistochemistry was applied to detect the expression of ERCC1, MSH2 and PARP1 in 111 cases of non-small cell lung cancer paraffin embedded surgical specimens. Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MSH2, PARP1 and the related clinicopathological factors. COX regression analysis was used to determine whether ERCC1, MSH2 and PARP1 were independent prognostic factors. In the enrolled 111 non-small cell lung cancer patients, the positive expression rate of ERCC1, MSH2 and RARP1 was 33.3%, 36.9% and 55.9%, respectively. ERCC1 (P<0.001) and PARP1 (P=0.033) were found to be correlated with the survival time while there was no correlation for MSH2 (P=0.298). Patients with both ERCC1 and PARP1 negative cancer had significantly longer survival time than those with ERCC1 (P=0.042) or PARP1 (P=0.027) positive alone. Similalry, the survival time of patients with both ERCC1 and PARP1 positive cancer was shorter than those with ERCC1 (P=0.048) or PARP1 (P=0.01) positive alone. Patients with ERCC1 or PARP1 negative non-small cell lung cancer appear to benefit from platinum-based postoperative adjuvant chemotherapy.

Highlights

Lung cancer is one of the most common malignances, of which the occurrence and mortality is increasing every year due to air pollution, environmental breakdown and cigarette abuse (Jemal et al, 2005; 2006)
Through og-rank survival analysis, we evaluated the prognostic value of the ERCC1, MutS protein homolog 2 (MSH2), poly ADP-ribose polymerase 1 (PARP1) and the related clinicopathological factors
It was reported that platinumbased adjuvant chemotherapy increased the five year survival rate by 4.1% in the 1867 Non-small cell lung cancer (NSCLC) patients from International Adjuvant Lung Cancer Trail (IALT) (Arriagada et al, 2004)

Summary

Introduction

Lung cancer is one of the most common malignances, of which the occurrence and mortality is increasing every year due to air pollution, environmental breakdown and cigarette abuse (Jemal et al, 2005; 2006). Multiple DNA repair pathways have already been confirmed to be associated with tumor prognosis, drug efficacy or chemotherapeutic resistance, including base excision repair (BER), mismatch repair (MMR), translesion synthesis, nucleotide excision repair (NER) and homologous recombination (HR) (Scartozzi et al, 2006; Wang et al, 2009). ADP-ribose polymerase (PARP), involved in BER pathway, is demonstrated to be associated with resistance to platinum drugs and prognosis in NSCLC patients (Kummar et al, 2012). It is proposed that DNA repair pathways affect the resistance of NSCLC patients to platinum-based chemotherapy. We assessed the relationships between the expression of ERCC1, MSH2 and PARP1 and clinical variables, including gender, age, smoking history, histologic type, TNM stage and tumor size, in NSCLC patients. The prognostic values of these proteins were evaluated in NSCLC patients treated with platinum-based postoperative adjuvant therapy

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