Association between EGFR mutations and ERCC1 expression in NSCLC

Gandara and colleagues from UC Davis Cancer Center have published ahead-of-print on October 21, 2010 in Journal of Thoracic Oncology an interesting article examining the association between EGFR activating mutations and ERCC1 gene expression in NSCLC.

NSCLC tumors that show EGFR activating mutations are also more likely to show low expression of ERCC1 mRNA levels according to this study.  This might explain (at least in part) the clinical observation that suggest enhanced efficacy of platinum-based chemotherapy in patients with EGFR-mutant NSCLCs.

The authors performed microdissection of tumors from 1207 patients with NSCLC and analyzed EGFR mutation by allele-specific by PCR and ERCC1 mRNA expression by RT-PCR.

Median ERCC1 expression was histology-related: adenocarcinoma (ADC) showed a lower median expression (1.68 (0.22-11.31) versus squamous cell carcinoma (SQC) (2.42 (0.51-14.28) (p<0.001).  The presence of EGFR mutations was highly associated with low ERCC1 expression (p<0.001).

It would be interesting if future or additional work focused specifically on ADC as a subgroup and perhaps the authors might consider re-analyzing their data and presenting this data.  I suggest this as a practical concern since we are not routinely testing SQC for EGFR mutation.  In addition, the next step is to examine the relationship between EGFR mutation and low versus high ERCC1 expression and response to combined EGFR-TKI and platinum-based chemotherapy, especially in advanced stage disease.

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[Hollyanne]

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