MOLECULAR-GENETICS FOR CLINICAL MANAGEMENT OF COLORECTAL-CARCINOMA

Background. The molecular genetic changes associated with colorectal c arcinoma are among the best understood of any common human cancer. The genetic changes during the late stages of colorectal carcinomas may b e useful in clinical management for determining the metastatic potenti al of the carcinoma. Methods. Tumor tissues were evaluated by restrict ion fragment length polymorphism (RFLP) analysis of chromosomes 5q, 17 p, 18q, and 22q (n = 98), by reverse transcription-polymerase chain re action (RT-PCR) analysis of messenger RNA expression of the DCC gene ( deleted in colorectal carcinoma) (n = 27) and by immunohistochemical a nalysis of p53 protein expression (n = 44). Results. Loss of heterozyg osity (LOH) on chromosomes 17p, 18q, and 22q, but not on 5q, was much more frequently detected in advanced carcinomas than in intramucosal c arcinomas (P < 0.01). 17p LOH was significantly correlated with vascul ar invasion (P < 0.001), whereas 18q LOH was correlated with lymphatic invasion and hepatic metastasis (P < 0.01), and 22q LOH was correlate d with lymph node metastasis (P < 0.05). LOH on 5q did not show a sign ificant correlation with any factors of tumor invasion or metastasis. DCC expression was not observed in any of five hepatic metastasis or i n five of seven advanced carcinomas that were accompanied by hepatic m etastasis (10 of 12). However, a similar lack of expression was observ ed in only 5 of 15 carcinomas without hepatic metastasis (P < 0.05), p 53 Expression was found to vary in both primary and metastatic carcino mas by immunohistochemistry. Conclusions. The clinical application of molecular genetics (i.e., RFLP analysis of chromosome 17p, 18q, and 22 q and RT-PCR analysis of DCC expression into messenger RNA) can be use d to determine the metastatic potential of colorectal carcinomas.