Loss of heterozygosity in BRCA1 and BRCA2 markers and high-grade malignancy in breast cancer

Loss of heterozygosity (LOH) in loci of the 17q21 and 13q12-13 regions can collaborate in the inactivation of BRCA1, BRCA2, and possibly other genes i mplicated in the pathogenesis of breast carcinomas. We investigate allelic losses in microsatellites of the BRCA1 and BRCA2 regions, and their correla tions with seven pathologic parameters in 140 breast carcinomas. Those case s showing LOH in the region of the RE gene, 13q14, were excluded from the s tudy. The LOH analysis was performed by amplifying DNA by PCR, using four m arkers of the 17q21 region (D17S856, D17S855, D17S1323, and D17S1327) and f our markers of the 13q12-13 region (D13S290, D13S260, D13S310, and D13S267) . LOH in the BRCA1 region was found in 47% of tumors, correlating significa ntly with estrogen receptor content (p = 0.025), progesterone receptors (p = 0.004), higher grade (p = 0.0008), peritumoral vessel invasion (p = 0.001 ), and lymph node metastases (p = 0.002). When we excluded the cases with L OH in the BRCA2 region and those not informative for it, the significance d isappeared. In the BRCA2 region, a rate of LOH of 51% was found; it correla ted significantly with estrogen receptor content (p = 0.002), progesterone receptors (p = 0.03), peritumoral vessel invasion (p = 0.005), higher grade (p = 0.002), and lymph node metastases (p = 0.001). When cases with BRCA1 losses and those not informative were excluded, again the significance disa ppeared. Concomitant losses in the BRCA1 and BRCA2 regions were found in 32 % of cases, correlating significantly with lymph node metastases (p = 0.000 2), estrogen receptor content (p = 0.003), progesterone receptors (p = 0.00 1), histologic grade (p = 0.01), and peritumoral vessel invasion (p = 0.000 4). These results suggest that concomitant losses in both regions could hav e a functional effect, influencing the presence of a poor tumor pathophenot ype in breast carcinomas.