Loss of c-met protooncogene in primary and metastatic sites of breast cancer.
BACKGROUND
It has been proposed that clones of tumor cells acquire higher metastatic potential as a result of specific genetic alterations. This study was designed to determine the role of the c-met protooncogene in systemic spread by comparing the loss of the c-met protooncogene between primary and metastatic breast carcinomas.


METHODS
Only patients who had not received chemotherapy or radiotherapy in the preceding 6 months were included in this study. Histologically proven malignant tissue was obtained from the primary tumor, involved nodes, and distant metastatic and recurrent tumors of patients with breast carcinomas. Allelic loss of the c-met protooncogene in tumor tissue was determined by Southern blotting using a polymerase chain reaction-generated 347-bp human met-H probe. Restriction digestion was performed using Taq I and Msp I, with the patient's lymphocyte DNA as controls.


RESULTS
Of 52 patients, lymphocyte DNA from 36 patients was heterozygous for the c-met protooncogene (69% informative). Forty-six tumors from these 36 patients were analyzed. Four of 30 primary tumors (13%) showed allelic loss of c-met. Of the nine nodal metastases examined, three (33%) showed allelic loss of the c-met protooncogene. Of seven distant metastatic breast tumors or recurrent disease, two (29%) showed allelic loss (both in patients with skin metastasis in the chest wall).


CONCLUSIONS
Allelic loss of the c-met protooncogene was detected in both primary (13%) and metastatic sites (31%) of breast cancer. Although a higher proportion of allelic loss of c-met was noted in nodal and distant/recurrent disease, the difference when compared with the primary tumor was not statistically significant. These findings indicate a limited role of the c-met protooncogene in breast cancer metastases.
Ng
E H
EH
Department of Surgery, Singapore General Hospital, Singapore.
Pey
H B
HB
Law
H Y
HY
Ng
I
I
Ji
C Y
CY
Lin
V
V
Soo
K C
KC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D015139:Blotting, Southern; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D002277:Carcinoma / Q000235:genetics* / Q000556:secondary / Q000628:therapy; D003131:Combined Modality Therapy; D015342:DNA Probes / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D016133:Polymerase Chain Reaction; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics*; D012189:Retrospective Studies
D015342:DNA Probes; D004273:DNA, Neoplasm; D019859:Proto-Oncogene Proteins c-met