Does Neoadjuvant Therapy Alter KRAS and/or MSI Status in Rectal Adenocarcinoma?
SO Ondrejka, DF Schaeffer, MA Jakubowski, DA Owen, MP Bronner. Cleveland Clinic, Cleveland, OH; The University of British Columbia, Vancouver, BC, Canada
Background: To our knowledge, the genotoxic effect of neoadjuvant chemoradiation therapy on tumor molecular diagnostic testing is unknown. This study examines rectal adenocarcinomas both pre and post neoadjuvant treatment to assess whether it alters MSI and KRAS results. These two tests significantly impact rectal cancer management, based on the hereditary and prognostic aspects of MSI status and because both KRAS and MSI predict response to therapy. If genotoxic neoadjuvant treatment were to modify the results of these molecular tests, then the resultant testing inaccuracy could mislead clinical decision-making. This study examines this unexplored issue.
Design: A total of 18 rectal adenocarcinoma patients with available pre and post treatment material were selected for this multi institutional study. DNA was extracted from microdissected rectal adenocarcinomas and paired normal tissues from both pretreatment biopsies and post-treatment resection specimens. MSI testing utilized the revised NCI panel of 5 mononucleotide repeat markers, comparing cancers to matched normal control tissues and defining microsatellite stable (MSS) as 5 stable markers and microsatellite instability high (MSI-H) as >2 unstable markers. KRAS codon 12 and 13 point mutations were examined by PCR and bidirectional sequencing.
Results: MSI and KRAS results were unchanged comparing rectal cancers before and after chemoradiotherapy in all 18 patients (p= 1.000; 95% CI: 0.3969 to 2.520). All 18 tumors (100%) were MSS. KRAS testing identified 12 (67%) wild-type tumors and 6 (33%) mutated tumors with identical KRAS mutations pre and post treatment. These MSI and KRAS mutational prevalences parallel those in the reported rectal cancer literature.
Conclusions: Neoadjuvant therapy does not appear to cause significant artifactual genetic alterations in treated rectal adenocarcinoma, indicating that either untreated rectal cancer biopsies or post-treatment resection specimens are appropriate for testing.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 102, Monday Morning