LOSS OF C-MET PROTOONCOGENE IN PRIMARY AND METASTATIC SITES OF BREAST-CANCER

Background: It has been proposed that clones of tumor cells acquire hi gher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncog ene in systemic spread by comparing the loss of the c-met protooncogen e between primary and metastatic breast carcinomas. Methods: Only pati ents who had not received chemotherapy or radiotherapy in the precedin g 6 months were included in this study. Histologically proven malignan t tissue was obtained from the primary tumor, involved nodes, and dist ant metastatic and recurrent tumors of patients with breast carcinomas . Allelic loss of the c-met protooncogene in tumor tissue was determin ed by Southern blotting using a polymerase chain reaction-generated 34 7-bp human met-H probe. Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls. Results: O f 52 patients, lymphocyte DNA from 36 patients was heterozygous for th e c-met protooncogene (69% informative). Forty-six tumors from these 3 6 patients were analyzed. Four of 30 primary tumors (13%) showed allel ic loss of c-met. Of the nine nodal metastases examined, three (33%) s howed allelic loss of the c-met protooncogene. Of seven distant metast atic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall). Conclusion s: Allelic loss of the c-met protooncogene was detected in both primar y (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/re current disease, the difference when compared with the primary tumor w as not statistically significant. These findings indicate a limited ro le of the c-met protooncogene in breast cancer metastases.