ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer

Tetsuya Fujii, Shinichi Toyooka, Kouichi Ichimura, Yoshiro Fujiwara, Katsuyuki Hotta, Junichi Sou, Hiroshi Suehisa, Naruyuki Kobayashi, Motoi Aoe, Tadashi Yoshino, Katsuyuki Kiura, Hiroshi Date

Research output: Contribution to journalArticle

77 Citations (Scopus)

Abstract

The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P = 0.013; pathological effectiveness; 100% vs. 47.1%, P = 0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.

Original languageEnglish
Pages (from-to)377-384
Number of pages8
JournalLung Cancer
Volume59
Issue number3
DOIs
Publication statusPublished - Mar 2008

Fingerprint

Non-Small Cell Lung Carcinoma
DNA Repair
Cisplatin
Drug Therapy
irinotecan
Proteins
Chemoradiotherapy
BRCA1 Protein
docetaxel
Neoplasms
Neoadjuvant Therapy
Survival
Disease-Free Survival
Thorax
Retrospective Studies
Lymph Nodes
Radiation
Therapeutics

Keywords

  • BRCA1
  • Cisplatin
  • ERCC1
  • Neoadjuvant therapy
  • NSCLC
  • Radiation

ASJC Scopus subject areas

  • Oncology

Cite this

ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer. / Fujii, Tetsuya; Toyooka, Shinichi; Ichimura, Kouichi; Fujiwara, Yoshiro; Hotta, Katsuyuki; Sou, Junichi; Suehisa, Hiroshi; Kobayashi, Naruyuki; Aoe, Motoi; Yoshino, Tadashi; Kiura, Katsuyuki; Date, Hiroshi.

In: Lung Cancer, Vol. 59, No. 3, 03.2008, p. 377-384.

Research output: Contribution to journalArticle

Fujii, Tetsuya ; Toyooka, Shinichi ; Ichimura, Kouichi ; Fujiwara, Yoshiro ; Hotta, Katsuyuki ; Sou, Junichi ; Suehisa, Hiroshi ; Kobayashi, Naruyuki ; Aoe, Motoi ; Yoshino, Tadashi ; Kiura, Katsuyuki ; Date, Hiroshi. / ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer. In: Lung Cancer. 2008 ; Vol. 59, No. 3. pp. 377-384.
@article{cc344ece9cfe49288af149dce6b3182b,
title = "ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer",
abstract = "The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100{\%} vs. 42.8{\%}, P = 0.013; pathological effectiveness; 100{\%} vs. 47.1{\%}, P = 0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.",
keywords = "BRCA1, Cisplatin, ERCC1, Neoadjuvant therapy, NSCLC, Radiation",
author = "Tetsuya Fujii and Shinichi Toyooka and Kouichi Ichimura and Yoshiro Fujiwara and Katsuyuki Hotta and Junichi Sou and Hiroshi Suehisa and Naruyuki Kobayashi and Motoi Aoe and Tadashi Yoshino and Katsuyuki Kiura and Hiroshi Date",
year = "2008",
month = "3",
doi = "10.1016/j.lungcan.2007.08.025",
language = "English",
volume = "59",
pages = "377--384",
journal = "Lung Cancer",
issn = "0169-5002",
publisher = "Elsevier Ireland Ltd",
number = "3",

}

TY - JOUR

T1 - ERCC1 protein expression predicts the response of cisplatin-based neoadjuvant chemotherapy in non-small-cell lung cancer

AU - Fujii, Tetsuya

AU - Toyooka, Shinichi

AU - Ichimura, Kouichi

AU - Fujiwara, Yoshiro

AU - Hotta, Katsuyuki

AU - Sou, Junichi

AU - Suehisa, Hiroshi

AU - Kobayashi, Naruyuki

AU - Aoe, Motoi

AU - Yoshino, Tadashi

AU - Kiura, Katsuyuki

AU - Date, Hiroshi

PY - 2008/3

Y1 - 2008/3

N2 - The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P = 0.013; pathological effectiveness; 100% vs. 47.1%, P = 0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.

AB - The excision repair cross-complementation group 1 (ERCC1) and BRCA1 have been identified as predictors of clinical outcomes among patients with non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy. In this study, we immunohistochemically examined the ERCC1 and BRCA1 protein expression levels in 35 patients with metastatic mediastinal lymph nodes obtained prior to treatment as retrospective study. These patients had been enrolled in our studies on neoadjuvant chemotherapy with cisplatin and irinotecan (15 patients) or chemoradiotherapy with cisplatin and docetaxel plus concurrent thoracic radiation (20 patients). The relations between the ERCC1 or BRCA1 protein expression and the clinical outcomes of the patients were then examined. The rates of radiological response and pathological effectiveness were significantly higher among patients with ERCC1-negative tumors, compared with those with positive tumors in the neoadjuvant chemotherapy group (radiological response rates; 100% vs. 42.8%, P = 0.013; pathological effectiveness; 100% vs. 47.1%, P = 0.038), but no associations were observed in the neoadjuvant chemoradiotherapy group. Regarding survival, no significant differences in overall survival or disease-free survival were observed between patients with ERCC1-negative and positive tumors in both the neoadjuvant chemotherapy and chemoradiotherapy groups. In summary, we showed that a ERCC1-negative protein status was significantly related to tumor responsiveness to neoadjuvant chemotherapy with cisplatin and irinotecan, but such a status was not a clear prognostic predictor to cisplatin-based neoadjuvant therapy in NSCLC patients. Further study is needed to clarify the value of molecular predictors for customizing therapy for patients with NSCLC.

KW - BRCA1

KW - Cisplatin

KW - ERCC1

KW - Neoadjuvant therapy

KW - NSCLC

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=40249094603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=40249094603&partnerID=8YFLogxK

U2 - 10.1016/j.lungcan.2007.08.025

DO - 10.1016/j.lungcan.2007.08.025

M3 - Article

VL - 59

SP - 377

EP - 384

JO - Lung Cancer

JF - Lung Cancer

SN - 0169-5002

IS - 3

ER -