Expression of proliferation-specific genes in the mucosa adjacent to colon carcinoma.

BACKGROUND

One of the main concerns in colon carcinoma therapy is local recurrence of the malignancy at the site of resection. Previous studies have shown that morphologically normal-appearing mucosa adjacent to colon carcinoma is different from mucosa distant from carcinoma. Mucosa adjacent to a carcinoma is characterized by crypt lengthening, cell hypertrophy, and change in production of mucopolysaccharides from sulfomucin in normal mucosa to sialomucins in carcinomas and adjacent mucosa. Recently there have been reports suggesting that there is an upward extension of the proliferative compartment in colonic crypts of this adjacent mucosa.

METHODS

Immunoblot analysis using antibodies to retinoblastoma, statin, c-Fos, c-Jun, and Cdc-2 proteins was used for our study on the expression of early cell cycle genes in carcinoma and its adjacent mucosa. In all, 15 tissue samples obtained from patients with colon carcinoma were analyzed. Tissue specimens were collected and immediately dissected as tumor, 0 to 1, 1 to 2, 2 to 3, 3 to 4, and 4 to 5 cm from the primary lesion. Dissected pieces were homogenized separately and subjected to immunoblot analysis.

RESULTS

We found upregulation of c-Fos, c-Jun, and Cdc-2 expression in carcinoma and adjacent mucosa up to 4 cm from the edge of the carcinoma. The phosphorylated form of retinoblastoma is present in the carcinoma as well as in adjacent mucosa up to 4 cm from the margin of the carcinoma. Furthermore, we observed that the level of statin, a nonproliferation-specific nuclear protein, is very low in the primary lesion and in adjacent mucosa up to 3 cm.

CONCLUSIONS

These results indicate that adjacent tissue up to 3 to 4 cm from the carcinoma has elevated levels of expression for cell cycle traverse-associated genes and down-regulation of nonproliferation-specific gene expressions such as statin. This imbalance indicates that within 3 to 4 cm from the edge of the carcinoma, colonic epithelial cells are already abnormal and may be in the hyperproliferative and preneoplastic state, susceptible to further steps leading to eventual malignant transformation.