Clinicopathological characteristics of breast carcinomas with allelic loss in the p73

Abstract

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 primary human tumors. Allelic loss studies involving the 1p arm in breast carcinomas 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 correlations with patient age and 10 pathologic parameters in a series of 193 breast carcinomas. The LOH analysis was performed by amplifying DNA by PCR, using the five markers of the 1p 36 region (p73P1, D1S2694, D1S214, D1S2666 and D1S450). LOH was found in at least one of these markers in 27% of tumors. When we established the comparison between tumors with and without LOH and the distribution of the 10 pathologic parameters considered, we observed statistically significant differences in association with higher histologic grade (p = 0.02), more advanced pathological stage (p = 0.02), peritumoral vessel involvement (p = 0.04) and poorly differentiated carcinomas (p = 0.01), as well as in tumors that concomitantly exhibited lymph node metastases, peritumoral vessel involvement and absence of steroid receptors (p = 0.02). These data suggest that LOH in the p73 region could be pathogenically related to breast cancer and possibly to a poor tumor prognosis.

Increased choline kinase activity in human breast carcinomas: clinical evidence for a potential novel antitumor strategy

“…Tumor size, lymph node metastases and stage were assessed using the TNM classi®cation. Tumors were graded according to the Bloom ± Richardson grading system (Dominguez et al, 2000). Steroid receptor content was determined by an immunohistochemical procedure, the results of which were considered to be positive when 25% or more of the cells stained positively.…”

A família do p53: aspectos estruturais e funcionais do p73 e do p63

“…A perda de alelos no braço 1p é observada em 13% a 75% dos carcinomas mamários, conforme o intervalo gênico estudado. Tumores com essas perdas apresentam pior prognóstico, apresentando alto grau histológico, invasão angiolinfática peritumoral e ausência de receptores hormonais (13). De fato, a perda da heterozigosidade do p73 foi verificada em carcinomas mamários de mau prognóstico (1, 13).…”

Ανάλυση των μεταγραφικών επιπέδων των γονιδίων ΤΡ53, ΤΡ63 και ΤΡ73 και των ισομορφών ΤΑp63, ΔΝp63, ΤΑp73 και ΔΝp73 στον καρκίνο της ουροδόχου κύστεως

“…In breast cancers, TP73 LOH has been detected at frequencies ranging from 13% to at least 27% [196,221,222]. In a cohort of 193 breast carcinoma patients, TP73 LOH was significantly associated with higher tumor grade and advanced stage, with peritumoral vessel involvement and with tumors exhibiting lymph node metastases [221].…”

“…In breast cancers, TP73 LOH has been detected at frequencies ranging from 13% to at least 27% [196,221,222]. In a cohort of 193 breast carcinoma patients, TP73 LOH was significantly associated with higher tumor grade and advanced stage, with peritumoral vessel involvement and with tumors exhibiting lymph node metastases [221]. Also, Ahomadegbe et al reported significantly higher TP73 LOH frequency in inflammatory breast carcinomas (IBC), which are characterized by very poor prognosis, when compared to their counterparts with no inflammatory symptoms (NBC) [223].…”

“…Overall, ΔNp73 mRNA was not detected in 3 tissue pairs. Loss of heterozygosity (LOH) in 1p36, where TP73 is located, has frequently been reported in neuroblastomas and other nervous system tumors [159,185,186,189,194], in breast cancers [196,[221][222][223], in hepatocellular [201,202,224] and ovarian carcinomas [211,[226][227][228], but not in bladder tumors. Apart from that, TP73 mutations that are required to completely inactivate the remaining allele have rarely been detected in bladder malignancies [219,234].…”