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Multiple Detection of Genetic Alterations in Tumors and Stool

Istituto Oncologico Romagnolo [C. R., D. C.], Divisione di Gastroenterologia, Ospedale Morgagni [P. M.], and Divisioni di Anatomia Patologica [L. S.] e Oncologia [D.A.], Ospedale Pierantoni, Forlì, Italy

Detection of genetic alterations in exfoliated intestinal cells in stool could represent an alternative, noninvasive tool for the screening of colorectal tumors. To verify this, we analyzed p53 and K-ras mutations and microsatellite instability on 46 cases of colorectal cancer and compared the presence of molecular alterations in tumor tissue and stool samples from individual patients. p53 exons 5–8 and K-ras exons 1–2 were analyzed by denaturing gradient gel electrophoresis. For the microsatellite instability, a set of 5 microsatellite markers (D2S123, D5S346, D17S250, BAT25, and BAT26) was evaluated. In the 18 healthy individuals, no genetic alterations in either tissue or stool were detected. p53 mutations were detected in 17 (37%), K-ras alterations in 15 (33%), and microsatellite instabilities in 5 (11%) of the 46 tumors analyzed. In a side study, we analyzed the correlation in genetic alteration profiles between tumors and macroscopically normal or healthy tissue from the same patient. The presence of at least one molecular alteration in tumor was observed in 31 (67%) of the cases. p53, K-ras mutations, and microsatellite instabilities were detected in stool samples in 18, 40, and 60% of patients with tumors harboring the same alterations. Due to the largely complementary presence of p53 and K-ras mutations in tumors, the use of highly sensitive procedures for stool analysis could offer a means competitive with colonoscopy and the fecal occult blood test.

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