Reduction of telomeric length and c-erbb-2 gene amplification in human breast cancer, fibroadenoma, and gynecomastia. Relationship to histologic grade and clinical parameters

Abstract

BACKGROUND: Telomeric deletions contribute to genetic instability and may represent an important mechanism of carcinogenesis. Amplification of the c-erbB-2 gene has been demonstrated in breast carcinoma. The clinical significance of telomeric deletions and c-erbB-2 gene amplification therefore was studied in patients with breast disorders. METHODS: The Southern blot analysis was used to measure telomeric length as well as the c-erbB-2 gene amplification of breast carcinomas, adjacent normal breast tissues, fibroadenomas, and cases of gynecomastia. RESULTS: Significant reductions in telomeric length and concentration were observed in all breast tissues when compared to placental DNA. Mean telomeric lengths were lowest in carcinomas and fibroadenomas. There were no significant differences, however, in the telomeric lengths among tissues from patients with breast carcinomas, fibroadenomas, or gynecomastia. The degree of telomeric deletion correlated significantly with histologic grade and was most notable in Grade 3 (scirrhous) breast carcinoma. The extent of telomeric deletion reflects the histologic aggressiveness of breast carcinoma, and telomeric reduction already can be seen in the adjacent normal breast tissues from patients with breast cancer. c-erbB-2 gene amplification was observed in 26.8% of the patients with breast carcinoma. c-erbB-2 gene amplification was not observed, however, in patients with fibroadenomas or gynecomastia. The degree of telomeric deletion did not correlate with c-erbB-2 gene amplification, tumor size, clinical stage, steroid receptors, or prognosis. Telomeric length was shorter in lymph node-negative tumors than in lymph node-positive tumors. CONCLUSIONS: These findings indicate that a shorter telomere length reflects growth advantage in breast cancer tissue, and telomeric reduction may promote cancer progression.