To our knowledge, the genotoxic effects of
neoadjuvant chemoradiation therapy on molecular diagnostic testing results are unknown. However, if
neoadjuvant treatments were to alter molecular test results, clinical decision-making could be misled. This raises questions about the appropriateness of using posttreatment
tumor for testing. To address this, rectal
adenocarcinomas both before and after
neoadjuvant treatment were evaluated for alterations in KRAS and
microsatellite instability (MSI) testing.
Neoadjuvant chemoradiation therapy is common in this
tumor type, and alterations in these 2 tests would significantly impact management. A total of 17 rectal
adenocarcinoma patients with available pretreatment and posttreatment
tumor were studied. MSI testing used the revised National Cancer Institute panel of 5 mononucleotide microsatellite repeats, comparing
cancers with matched normal control tissues. KRAS
codon 12-point and 13-point mutations were examined by polymerase chain reaction amplification and bidirectional sequencing. MSI and KRAS results were unchanged comparing
rectal cancer tissue before and after
chemoradiotherapy in all 17 patients (P=1.000; 95% CI: 0.3969-2.520). All 17
tumors (100%) were microsatellite stable. KRAS testing identified 12 (72%) wild-type
tumors and 5 (28%)
codon 12 or 13 mutant
tumors with identical KRAS point mutations before and
after treatment. The identified MSI and KRAS mutational prevalences parallel those reported in the
rectal cancer literature.
Neoadjuvant therapy did not alter KRAS
codon 12 or 13 or MSI results in rectal
adenocarcinoma, providing evidence that either pretreatment biopsy or posttreatment resection tissues are appropriate for testing.