Prognostic potential of ERCC1 protein expression and clinicopathologic factors in stage III/N2 non-small cell lung cancer

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Abstract

Background

Pathological stage III/N ₂ non-small cell lung cancer (NSCLC) is heterogeneous, and the optimal prognostic marker for survival remains unclear in Chinese patients. The aim of the present study was to assess the prognostic value of the clinicopathologic features and excision repair cross-complementing group-1 (ERCC1) in resected p-stage III/N ₂ NSCLC patients that received cisplatin-based adjuvant chemotherapy.

Methods

Clinical data concerning 115 patients with histopathologically confirmed stage III/N ₂ NSCLC who underwent a complete resection were reviewed retrospectively. All patients received cisplatin-based adjuvant chemotherapy. The protein expression levels for ERCC1 were immunohistochemically examined in 115 patients. The relationship between the ERCC1 protein expression level and the clinical outcomes of the patients was then observed.

Results

The 5-year survival rate and median survival time of patients with pathological stage III/N ₂ NSCLC after surgery and postoperative chemotherapy was 27.0% and 28.0 months, respectively. Survival of patients with ERCC1 negative tumors was significantly longer than those with ERCC1 positive tumors (p = 0.004). However, it was not entirely clear whether adjuvant chemotherapy with cisplatin-based agents was beneficial for ERCC1-negative patients with p-stage III/N ₂. A multivariate analysis of survival in patients with stage III/N ₂ NSCLC showed that surgical procedure (pneumonectomy vs. lobectomy; p = 0.001), number of involved lymph nodes (≤5 vs. >5; p = 0.001) and ERCC1 protein expression (negative vs. positive; p = 0.012) were significant prognostic factors. In addition, the prognosis of patients with skip mediastinal lymph node metastasis showed a tendency for improved survival, but this was no significant (p = 0.432).

Conclusions

Findings from this retrospective study suggested that the number of involved lymph nodes and the type of pulmonary resection are significant and independent prognosis factors in patients with p-stage III/N ₂ NSCLC. In addition, it was found that ERCC1 protein expression might play an important role in the prognosis of p-stage III/N ₂ NSCLC patients treated with cisplatin-based adjuvant chemotherapy.

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Most cited references 24

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Cisplatin-based adjuvant chemotherapy in patients with completely resected non-small-cell lung cancer.

Rodrigo Arriagada, Bengt Bergman, Ariane Dunant … (2004)

On the basis of a previous meta-analysis, the International Adjuvant Lung Cancer Trial was designed to evaluate the effect of cisplatin-based adjuvant chemotherapy on survival after complete resection of non-small-cell lung cancer. We randomly assigned patients either to three or four cycles of cisplatin-based chemotherapy or to observation. Before randomization, each center determined the pathological stages to include, its policy for chemotherapy (the dose of cisplatin and the drug to be combined with cisplatin), and its postoperative radiotherapy policy. The main end point was overall survival. A total of 1867 patients underwent randomization; 36.5 percent had pathological stage I disease, 24.2 percent stage II, and 39.3 percent stage III. The drug allocated with cisplatin was etoposide in 56.5 percent of patients, vinorelbine in 26.8 percent, vinblastine in 11.0 percent, and vindesine in 5.8 percent. Of the 932 patients assigned to chemotherapy, 73.8 percent received at least 240 mg of cisplatin per square meter of body-surface area. The median duration of follow-up was 56 months. Patients assigned to chemotherapy had a significantly higher survival rate than those assigned to observation (44.5 percent vs. 40.4 percent at five years [469 deaths vs. 504]; hazard ratio for death, 0.86; 95 percent confidence interval, 0.76 to 0.98; P<0.03). Patients assigned to chemotherapy also had a significantly higher disease-free survival rate than those assigned to observation (39.4 percent vs. 34.3 percent at five years [518 events vs. 577]; hazard ratio, 0.83; 95 percent confidence interval, 0.74 to 0.94; P<0.003). There were no significant interactions with prespecified factors. Seven patients (0.8 percent) died of chemotherapy-induced toxic effects. Cisplatin-based adjuvant chemotherapy improves survival among patients with completely resected non-small-cell lung cancer. Copyright 2004 Massachusetts Medical Society

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Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB–IIIA non-small-cell lung cancer (Adjuvant Navelbine International Trialist Association [ANITA]): a randomised controlled trial

Jean-Yves Douillard, Rafael Rosell, Mario de Lena … (2006)

Whether adjuvant chemotherapy improves survival of patients with non-small-cell lung cancer (NSCLC) is not known. We aimed to compare the effect of adjuvant vinorelbine plus cisplatin versus observation on survival in patients with completely resected NSCLC. 840 patients with stage IB-IIIA NSCLC from 101 centres in 14 countries were randomly assigned to observation (n=433) or to 30 mg/m(2) vinorelbine plus 100 mg/m(2) cisplatin (n=407). Postoperative radiotherapy was not mandatory and was undertaken according to every centre's policy. The primary endpoint was overall survival. Analysis was by intention to treat. This trial is registered as an International Standard Randomised Controlled Trial, number ISRCTN95053737. 367 patients in the chemotherapy group and 431 in the control group received their assigned treatment. 301 (36%) patients had stage IB disease, 203 (24%) had stage II disease, and 325 (39%) had stage IIIA disease. Tolerance to chemotherapy mainly included neutropenia in 335 (92%) patients and febrile neutropenia in 34 (9%); seven (2%) toxic deaths were also recorded. Compliance was greater with cisplatin than with vinorelbine (median dose intensity 89% [range 17-108] vs 59% [17-100]). After a median follow-up of 76 months (range 43-116), median survival was 65.7 months (95% CI 47.9-88.5) in the chemotherapy group and 43.7 (35.7-52.3) months in the observation group. Adjusted risk for death was significantly reduced in patients assigned chemotherapy compared with controls (hazard ratio 0.80 [95% CI 0.66-0.96]; p=0.017). Overall survival at 5 years with chemotherapy improved by 8.6%, which was maintained at 7 years (8.4%). Adjuvant vinorelbine plus cisplatin extends survival in patients with completely resected NSCLC, better defining indication of adjuvant chemotherapy.

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Prognosis of 6644 resected non-small cell lung cancers in Japan: a Japanese lung cancer registry study.

T Miya, Hisao Asamura, T Goya … (2005)

For the scheduled future revision of the TNM staging system for lung cancer, it is important that the present 1997 version be evaluated in a large population. In 2001, the Japanese Joint Committee of Lung Cancer Registry sent a questionnaire to 320 Japanese institutions regarding the prognosis and clinicopathological profiles of patients who underwent the resection for primary lung neoplasms in 1994. We compiled the data for 7408 patients from 303 institutions (94.7%). Among these, 6644 patients with non-small cell histology were studied in terms of prognosis. The 5-year survival rate of the entire group was 52.6%. The 5-year survival rates by clinical (c-) stage were as follows: 72.1% for IA (n = 2423), 49.9% for IB (n = 1542), 48.7% for IIA (n = 150), 40.6% for IIB (n = 746), 35.8% for IIIA (n = 1270), 28.0% for IIIB (n = 366) and 20.8% for IV (n = 147). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The 5-year survival rates by pathological (p-) stage were as follows: 79.5% for IA (n = 2009), 60.1% for IB (n = 1418), 59.9% for IIA (n = 232), 42.2% for IIB (n = 757), 29.8% for IIIA (n = 1250), 19.3% for IIIB (n = 719) and 20.0% for IV (n = 259). The difference in prognosis between neighboring stages was significant except for between IB and IIA and between IIIB and IV. The survival curves of stages IB and IIA were almost superimposed in both c- and p-settings. These findings indicated that the present stages IB and IIA should be merged into the same stage category. Otherwise, the present TNM staging system seemed to well characterize the stage-specific prognosis in non-small cell lung cancer. The future revision should focus on the subdivision of stages I and II.

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Author and article information

Journal

Journal ID (nlm-ta): J Cardiothorac Surg

Journal ID (iso-abbrev): J Cardiothorac Surg

Title: Journal of Cardiothoracic Surgery

Publisher: BioMed Central

ISSN (Electronic): 1749-8090

Publication date Collection: 2013

Publication date (Electronic): 10 June 2013

Volume: 8

Page: 149

Affiliations

[1 ]Department of Oncology, Beijing Chao-Yang Hospital affiliated to Capital Medical University, Workers Stadium South Road, Beijing, China

[2 ]Department of Pathology, Beijing Chao-Yang Hospital affiliated to Capital Medical University, Workers Stadium South Road, Beijing, China

[3 ]Department of Hematology, Beijing Chao-Yang Hospital affiliated to Capital Medical University, Workers Stadium South Road, Beijing, China

Article

Publisher ID: 1749-8090-8-149

DOI: 10.1186/1749-8090-8-149

PMC ID: 3681661

PubMed ID: 23759026

SO-VID: 0ae4678d-4fd5-4d1e-848a-6079652ccd0b

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.