Clinicopathological characteristics of breast carcinomas with allelic lossin the p73 region

p73, a new member of the p53 family, has been mapped to chromosome 1p 36, a region where loss of heterozygosity (LOH) is frequently observed in primar y human tumors. Allelic loss studies involving the 1p arm in breast carcino mas offer rates ranging from 13% to 75%, depending on the genetic interval being studied. We investigated LOH in an intragenic microsatellite marker, and those centromerically flanking the p73 gene, at 1p 36, and their correl ations with patient age and 10 pathologic parameters in a series of 193 bre ast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, us ing five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D 1S450). LOH was found in at least one of these markers in 27% of tumors. Wh en we established the comparison between tumors with and without LOH and th e distribution of the 10 pathologic parameters considered, we observed stat istically significant differences in association with higher histologic gra de (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral ves sel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, p eritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically relat ed to breast cancer and possibly to a poor tumor prognosis.