REDUCTION OF TELOMERIC LENGTH AND C-ERBB-2 GENE AMPLIFICATION IN HUMAN BREAST-CANCER, FIBROADENOMA, AND GYNECOMASTIA - RELATIONSHIP TO HISTOLOGIC GRADE AND CLINICAL-PARAMETERS

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 cl inical significance of telomeric deletions and c-erbB-2 gene amplifica tion therefore was studied in patients with breast disorders. Methods. The Southern blot analysis was used to measure telomeric length as we ll as the c-erbB-2 gene amplification of breast carcinomas, adjacent n ormal breast tissues, fibroadenomas, and cases of gynecomastia. Result s. Significant reductions in telomeric length and concentration were o bserved in all breast tissues when compared to placental DNA. Mean tel omeric lengths were lowest in carcinomas and fibroadenomas. There were no significant differences, however, in the telomeric lengths among t issues from patients with breast carcinomas, fibroadenomas, or gynecom astia. The degree of telomeric deletion correlated significantly with histologic grade and was most notable in Grade 3 (scirrhous) breast ca rcinoma. The extent of telomeric deletion reflects the histologic aggr essiveness 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 patie nts with breast carcinoma. c-erbB-2 gene amplification was not observe d, however, in patients with fibroadenomas or gynecomastia. The degree of telomeric deletion did not correlate with c-erbB-2 gene amplificat ion, tumor size, clinical stage, steroid receptors, or prognosis. Telo meric length was shorter in lymph node-negative tumors than in lymph n ode-positive tumors. Conclusions. These findings indicate that a short er telomere length reflects growth advantage in breast cancer tissue, and telomeric reduction may promote cancer progression.