Molecular genetic changes associated with colorectal carcinogenesis are not prognostic for tumor regression following preoperative chemoradiation of rectal carcinoma.
OBJECTIVE
Preoperative chemotherapy and radiation has become the standard of care for many patients with rectal cancer. The therapy may have toxicity and delays definitive surgery. It would therefore be desirable to identify those cancers that will not regress with preoperative therapy. We assessed a series of rectal cancers for the molecular changes of loss of heterozygosity of the APC and DCC genes, K-ras mutations, and microsatellite instability, changes that have clearly been associated with rectal carcinogenesis.


METHODS
Diagnostic colonoscopic biopsies from 53 patients who received preoperative chemotherapy and radiation were assayed using polymerase chain reaction techniques followed by single-stranded conformation polymorphism and DNA sequencing. Regression of the primary tumor was evaluated using the surgically removed specimen.


RESULTS
Twenty-three lesions (45%) were found to have a high degree of regression. None of the molecular changes were useful as indicators of regression.


CONCLUSIONS
Recognized molecular changes critical for rectal carcinogenesis including APC and DCC loss of heterozygosity, K-ras mutations, and microsatellite instability are not useful as indicators of tumor regression following chemoradiation for rectal carcinoma.
Zauber
N Peter
NP
Department of Medicine, Saint Barnabas Medical Center, Livingston, NJ, USA. pzauber@gmail.com
Marotta
Steven P
SP
Berman
Errol
E
Grann
Alison
A
Rao
Maithili
M
Komati
Naga
N
Ribiero
Kezia
K
Bishop
D Timothy
DT
D000368:Aged; D001706:Biopsy; D015179:Colorectal Neoplasms / Q000235:genetics*; D003131:Combined Modality Therapy / Q000379:methods; D005260:Female; D017491:Genes, APC; D016163:Genes, DCC / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D053842:Microsatellite Instability; D018807:Polymorphism, Single-Stranded Conformational; D011300:Preoperative Care; D011379:Prognosis; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D012007:Rectum / Q000473:pathology; D012074:Remission Induction / Q000379:methods