[2019] Comparison of EGFR and KRAS Mutations between Pre- and Post-Chemotherapy Groups in Primary and Metastatic Lung Adenocarcinomas

Delicia Munfus-McCray, Rex Chin-Wei Yung, Julie Brahmer, Frederic Askin, Edward Gabrielson, Qing Kay Li. The Johns Hopkins Hospitals and Bayview Medical Center, Baltimore, MD; The Johns Hopkins Hospitals, Baltimore, MD

Background: EGFR and KRAS mutations are found in 10-20% and 20-30% of primary lung adenocarcinomas, respectively. It is well known that EGFR and KRAS mutations are associated with a beneficial response to tyrosine kinase inhibitor (TKI) therapy. Several recent studies have shown that treatment-induced changes is related to the acquired resistance to TKI, and pre-treatment with TKI may sensitize EGFR mutations in tumor cells. These data suggest that chemotherapy may affect the phenotype of tumor cells. In this study, we analyzed EGFR and KRAS mutation in both pre- and post-chemotherapy groups of primary and metastatic lung adenocarcinomas.
Design: Using the archives of a major medical institution from January 2006 to December 2010, 314 lung adenocarcinomas with EGFR and KRAS mutations were included. Mutation status was determined by sequencing Exons 18 to 21 of EGFR and Exon 2 of KRAS (codons 12 and 13). Clinical information was also correlated.
Results: Among 314 lung adenocarcinomas (55 cytologic and 259 surgical specimens), 279 tumors (170 primary and 109 metastatic lesions) had mutational studies prior to chemotherapy and 35 tumors (21 primary and 14 metastatic lesions) had mutational studies following chemotherapy. The most commonly used chemotherapy agents were: Carboplatin, Cisplatin and Taxol. There was no significant difference of EGFR and KRAS mutations in the primary lung adenocarcinoma pre- or post-chemotherapy. However, in unrelated metastatic tumors, EGFR and KRAS mutations in the pre-treated group were 13% and 36%, respectively. In contrast, in post chemo-treated group, EGFR and KRAS mutations were 36% and 7%, respectively.

EGFR and KRAS Mutations in Metastatic Lung Adenocarcinoma Pre- and Post-Chemotherapy.
 Pre-ChemotherapyPost-Chemotherapy
EGFR14 (13%)5 (36%)
KRAS39 (36%)2 (14%)
Wild type56 (51%)7 (50%)
Total109(100%)14(100%)



Conclusions: Our findings suggest that previous chemotherapy may potentially affect EGFR and KRAS mutational status in tumors, particularly metastatic tumors. The mechanism of this change is not fully understood. The effect may be multi-leveled in tumor cells, such as alteration of cellular protein expression and/or shift of mutational sites which can't be detected by current methods. Additional studies are needed to further investigate the mechanism and clinical significance of these findings.
Category: Pulmonary

Monday, March 19, 2012 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 292, Monday Morning

 

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