CLINICAL IMPACT OF DETECTION OF LOSS OF HETEROZYGOSITY OF BRCA1 AND BRCA2 MARKERS IN SPORADIC BREAST-CANCER

The development of familial and sporadic breast cancer is based on gen etic alterations of tumour-suppressor genes, for which loss of heteroz ygosity (LOH) is one mechanism of gene inactivation. To investigate LO H of BRCA1 (17q21) and BRCA2 (13q12-13) in sporadic breast cancer, pol ymerase chain reaction (PCR)-based fluorescent DNA technology for dete ction of microsatellite polymorphisms was applied. A total of 137 brea st cancer and 15 benign breast specimens with matched normal tissue we re examined. Fluorescent-labelled PCR products were analysed in an aut omated DNA sequencer (ALF(TM) Pharmacia). Losses at both loci were cor related with different histological types, age, tumour size, lymph nod e status, grading and steroid hormone receptor expression. [SHR: oestr ogen receptor (ER), progesterone receptor (PgR)]. For BRCA1 (D17S855, THRA1, D17S579) losses could be detected in invasive ductal carcinoma (IDC; n=108) in 32-38%, invasive lobular carcinoma (ILC: n=19) in 21-4 2% depending on the marker applied, but not in benign breast tumours ( n=15). Losses of BRCA1 markers correlated with larger tumour size, hig her grade, and PgR expression. For BRCA2 (D13S260, D13S267, D13S171) l osses could be detected in 108 IDCs in 30-38%, in 19 ILCs in 17-39% de pending on the marker applied, but not in benign breast rumours. Losse s of BRCA2 markers correlated only with higher grade. Microsatellite a nalyses combined with detection of fluorescent-labelled PCR products b y an automated laser DNA sequencer can be used for routine determinati on of LOH. In sporadic breast cancer, LOH of BRCA1 or BRCA2 does not a dd decisive prognostic value as stated For familiar breast cancer.