• J. Am. Coll. Surg. · Jun 2011

    Comparative Study

    Molecular diagnosis of response to neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

    • Zhenbin Chen, Marjun P Duldulao, Wenyan Li, Wendy Lee, Joseph Kim, and Julio Garcia-Aguilar.
    • Department of Surgery, City of Hope, Duarte, CA, USA.
    • J. Am. Coll. Surg. 2011 Jun 1; 212 (6): 10081017.e11008-1017.e1.

    BackgroundPathologic complete response (pCR) to neoadjuvant chemoradiation (CRT) is an important prognostic factor in locally advanced rectal cancer. However, it is uncertain if histopathological techniques accurately detect pCR. We tested a novel molecular approach for detecting pCR and compared it with current histopathological approaches.Study DesignPretreatment tumor biopsies and surgical specimens were collected from 96 patients with locally advanced rectal cancer treated with neoadjuvant CRT and surgery. Tumor response was categorized by tumor regression grade. Tumor DNA from pre-CRT tumor biopsies was screened for K-ras and p53 mutations. DNA from paired surgical specimens was then screened for the same mutations using highly sensitive polymerase chain reaction-based techniques.ResultsSixty-eight of 96 (71%) pretreatment biopsies harbored K-ras and/or p53 mutation; 36 (38%) had K-ras mutations, 52 (54%) had p53 mutations, and 20 (21%) carried both mutations. Of 70 patients with tumor regression grades 1 to 3, sixty-six (94%) had a concordant K-ras and p53 mutation profile in pre- and post-treatment tissues. Of 26 patients with tumor regression grade 0 (pCR), 12 had K-ras or p53 mutations in pretreatment biopsies. Of these, 2 (17%) patients had the same K-ras (n = 1) or p53 (n = 1) mutation detected in post-treatment tissue.ConclusionsSensitive molecular techniques detect K-ras and p53 mutations in post-CRT surgical specimens in some patients with a pCR. This suggests histopathological techniques might not be completely accurate, and some patients diagnosed with a pCR to CRT might have occult cancers cells in their surgical specimens.Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

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