PMID- 10502729 OWN - NLM STAT- MEDLINE DCOM- 19991021 LR - 20190708 IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 84 IP - 5 DP - 1999 Oct 22 TI - Genetic alterations in early-onset invasive breast carcinomas: correlation of c-erbB-2 amplification detected by fluorescence in situ hybridization with p53 accumulation and tumor phenotype. PG - 511-5 AB - p53 tumor-suppressor gene mutation and p53 protein over-expression have been reported with higher frequency in early-onset breast carcinomas (EOBC). Given the role attributed to normal p53 protein in DNA-repair mechanisms, other somatic genomic alterations would be expected to be associated with this abnormality. Amplification of the c-erbB-2 (HER-2/neu) oncogene and over-expression of the corresponding p185erbB-2 protein have been linked to prognosis and response to therapy in breast cancer. In a retrospective study of 62 formalin-fixed paraffin-embedded invasive EOBC (diagnosed at 35 years or less), the amplification status of the c-erbB-2 gene detected by fluorescence in situ hybridization (FISH) using a unique sequence probe was compared with p53 protein accumulation measured by immunohistochemistry (IHC) and phenotypic features. p185erbB2-protein expression was also detected by immunohistochemistry, together with estrogen-receptor (ER) and progesterone-receptor (PR) expression. The data for a sub-set of 33 node-negative EOBC cases were compared with 70 node-negative tumors diagnosed in women above 36 years of age. Compared with node-negative BC in older women, node-negative EOBC was significantly more likely to feature high grade, high proliferation rate, negative ER and/or PR and p53 over-expression (p < 0.05). A trend toward a higher incidence of c-erbB-2 amplification in EOBC (21% vs. 9%) reached near-significance (p = 0.07). In EOBC, c-erbB-2 amplification and p53 over-expression were not associated with high tumor grade or high cell-proliferation rate, in contrast to the significant associations of these markers in tumors in older women. Abnormalities in tumor markers, including c-erbB-2 gene amplification and p53-protein over-expression, occur at different rates in women with EOBC as compared with BC developing in older women. This finding may reflect a different pathogenesis for EOBC, and warrants further investigation. CI - Copyright 1999 Wiley-Liss, Inc. FAU - Fiche, M AU - Fiche M AD - University Hospital, Nantes, France. FAU - Avet-Loiseau, H AU - Avet-Loiseau H FAU - Heymann, M F AU - Heymann MF FAU - Moussaly, F AU - Moussaly F FAU - Digabel, C AU - Digabel C FAU - Joubert, M AU - Joubert M FAU - Classe, J M AU - Classe JM FAU - Dravet, F AU - Dravet F FAU - Fumoleau, P AU - Fumoleau P FAU - Ross, J AU - Ross J FAU - Maugard, C M AU - Maugard CM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Tumor Suppressor Protein p53) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Breast Neoplasms/*genetics MH - Female MH - *Gene Amplification MH - *Genes, erbB-2 MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Middle Aged MH - Phenotype MH - Receptor, ErbB-2/analysis MH - Tumor Suppressor Protein p53/*analysis EDAT- 1999/09/30 00:00 MHDA- 1999/09/30 00:01 CRDT- 1999/09/30 00:00 PHST- 1999/09/30 00:00 [pubmed] PHST- 1999/09/30 00:01 [medline] PHST- 1999/09/30 00:00 [entrez] AID - 10.1002/(SICI)1097-0215(19991022)84:5<511::AID-IJC11>3.0.CO;2-5 [pii] AID - 10.1002/(sici)1097-0215(19991022)84:5<511::aid-ijc11>3.0.co;2-5 [doi] PST - ppublish SO - Int J Cancer. 1999 Oct 22;84(5):511-5. doi: 10.1002/(sici)1097-0215(19991022)84:5<511::aid-ijc11>3.0.co;2-5.