Universität zu Köln

Gandara, David R., Grimminger, Peter ORCID: 0000-0002-1859-9213, Mack, Philip C., Lara, Primo N., Jr., Li, Tianhong, Danenberg, Peter V. and Danenberg, Kathleen D. (2010). Association of Epidermal Growth Factor Receptor Activating Mutations with Low ERCC1 Gene Expression in Non-small Cell Lung Cancer. J. Thorac. Oncol., 5 (12). S. 1933 - 1939. PHILADELPHIA: LIPPINCOTT WILLIAMS & WILKINS. ISSN 1556-0864

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Abstract

Introduction: Patients with non-small cell lung cancer (NSCLC) with cancers harboring activating mutations in the epidermal growth factor receptor (EGFR) show improved efficacy from EGFR tyrosine kinase inhibitors. Some clinical studies also suggest enhanced efficacy of platinum-based chemotherapy in patients with EGFR-mutant cancers. We investigated the relationship of EGFR mutation status and DNA repair capacity, as exemplified by excision repair cross-complementing 1 (ERCC1) gene expression, as a potential explanation for this observation. Methods: Microdissected formalin-fixed paraffin-embedded tumors from 1207 patients with NSCLC were analyzed by real-time polymerase chain reaction for mRNA expression levels of ERCC1 and for EGFR mutation status by an allele-specific polymerase chain reaction assay. Results: NSCLC subtype was adenocarcinoma (AC) in 712 patients, squamous in 175, and not otherwise specified or other in 320. EGFR activating mutations were detected in 183/1207 patients (15.2%). Median ERCC1 expression overall was 1.82 (range, 0.22-27.31) and was histology related: AC, median = 1.68 (0.22-11.33) and squamous, median = 2.42 (0.51-14.28) (p < 0.001). Using a previously defined reference level of <1.7, ERCC1 expression was categorized as low in 556 of 1207 patients (46.1%). The presence of EGFR mutations was highly associated with ERCC1 expression (p < 0.001). This association was retained when adjusting for AC histologic subtype (p = 0.001). Conclusions: NSCLC specimens harboring EGFR activating mutations are more likely to express low ERCC1 mRNA levels. Whether these findings translate into enhanced clinical efficacy of EGFR-mutant cancers to platinum-based chemotherapy remains to be determined.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gandara, David R. UNSPECIFIED UNSPECIFIED UNSPECIFIED Grimminger, Peter UNSPECIFIED orcid.org/0000-0002-1859-9213 UNSPECIFIED Mack, Philip C. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lara, Primo N., Jr. UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Tianhong UNSPECIFIED UNSPECIFIED UNSPECIFIED Danenberg, Peter V. UNSPECIFIED UNSPECIFIED UNSPECIFIED Danenberg, Kathleen D. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491816
DOI:	10.1097/JTO.0b013e3181fd418d
Journal or Publication Title:	J. Thorac. Oncol.
Volume:	5
Number:	12
Page Range:	S. 1933 - 1939
Date:	2010
Publisher:	LIPPINCOTT WILLIAMS & WILKINS
Place of Publication:	PHILADELPHIA
ISSN:	1556-0864
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EGFR MUTATIONS; PROLONGED SURVIVAL; GEFITINIB THERAPY; CHEMOTHERAPY; CISPLATIN; ERLOTINIB; REPAIR; RNA; GEMCITABINE; SENSITIVITY Multiple languages Oncology; Respiratory System Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49181