Detection of oncogene mutation from neoplastic colonic cells exfoliated in feces.
OBJECTIVE
Best chances of a cure from colorectal cancer are obtained before metastatic spread. Lack of specific tests allowing early diagnosis of the tumor accounts for investigation of gene alterations involved in carcinogenesis by a noninvasive method. In the present study, K-ras codons 12 and 13 mutations were studied in neoplastic cells shed from the bowel into the stool and those contained in the tumor and normal mucosa. Moreover, healthy patients and a few others with precancerous conditions were examined.


METHODS
Stool, tumor, and mucosa samples were taken from 25 patients with colorectal adenocarcinoma. Stool and mucosa samples were obtained from 11 healthy patients, and stool, pathologic bowel tissue, and normal mucosa samples were obtained from 3 patients with adenoma (1) or ulcerative colitis (2). Polymerase chain reaction amplification and restriction enzyme analysis were performed.


RESULTS
K-ras codon 12 mutations were detected in both tumor and stool samples of 10 cancer patients, and no gene alterations were observed in 14 patients. In one patient with a tumor, a mutation was shown in only the tumor tissue. The agreement rate in tumor and stool analysis was 96 percent. A normal pattern of K-ras codons 12 and 13 was observed in the bowel mucosa. All stool and mucosa samples from healthy patients were not altered in K-ras. Agreement was registered between samples taken from patients with preneoplastic lesions.


CONCLUSIONS
These preliminary findings show a high rate of accuracy in the investigation of K-ras alterations in the colorectal cells shed into the feces, suggesting that such an approach could be used to study other gene alterations and, prospectively, to identify early colorectal cancers.
Ratto
C
C
Catholic University-Policlinico A. Gemelli, Department of Clinica Chirurgica, Rome, Italy.
Flamini
G
G
Sofo
L
L
Nucera
P
P
Ippoliti
M
M
Curigliano
G
G
Ferretti
G
G
Sgambato
A
A
Merico
M
M
Doglietto
G B
GB
Cittadini
A
A
Crucitti
F
F
D000368:Aged; D000369:Aged, 80 and over; D003062:Codon; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D005243:Feces / Q000166:cytology*; D005260:Female; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D015183:Restriction Mapping
D003062:Codon; D004273:DNA, Neoplasm