PMID- 15196531 OWN - NLM STAT- MEDLINE DCOM- 20040824 LR - 20141120 IS - 0959-8049 (Print) IS - 0959-8049 (Linking) VI - 40 IP - 10 DP - 2004 Jul TI - Expression of HER2 and its association with AP-2 in breast cancer. PG - 1485-95 AB - The aim of the study was to investigate the relationship between the expression of human epidermal growth factor receptor 2 (HER2) and activator protein 2 (AP-2), as well as the prognostic significance of HER2 in breast cancer. HER2 and AP-2 expressions were immunohistochemically (IHC) analysed in a large prospective, consecutive series of 425 breast cancer patients diagnosed and treated between 1990 and 1995 at the Kuopio University Hospital, Kuopio, Finland. In a subset of patients (n = 71), the gene amplification status was examined by using a chromogenic in situ hybridisation (CISH) analysis. Expression of HER2 was studied in relation to AP-2, clinicopathological parameters and patients' survival. Pathological membranous overexpression of the HER2 receptor was seen in 13% of the carcinomas, which was related both to gene amplification (78% of the cases) and high nuclear expression of AP-2 (67%, P = 0.007). HER2-positivity was most often seen in carcinomas having both high nuclear and high cytoplasmic AP-2 expression (P < 0.001). In the univariate survival analyses HER2-positivity predicted a shorter recurrence-free survival (RFS) (P < 0.0001) and a shorter breast cancer-related survival (BCRS) (P = 0.0063) in the whole patient group, as well as in the subgroup of node-negative patients. In the node-positive patients, HER2-positivity predicted only a shorter RFS. Combined expression of HER2 and nuclear AP-2 resulted in the separation of four groups with different prognoses, the best prognosis being for patients in the HER2-/AP-2+ group and the worse prognosis for those in the HER2+/AP-2- group. In the multivariate survival analyses, HER2-positivity independently predicted a shorter RFS in the whole patient group (P = 0.0067), as well as in the subgroup of node-positive patients (P = 0.0209). In conclusion, pathological membranous overexpression of the HER2 receptor in breast cancer is related both to gene amplification and a high AP-2 expression. Combining HER2 and AP-2 expressions may provide valuable information on the prognosis of breast cancer patients. FAU - Pellikainen, J AU - Pellikainen J AD - Department of Pathology, Kuopio University Hospital, Kuopio, Finland. FAU - Naukkarinen, A AU - Naukkarinen A FAU - Ropponen, K AU - Ropponen K FAU - Rummukainen, J AU - Rummukainen J FAU - Kataja, V AU - Kataja V FAU - Kellokoski, J AU - Kellokoski J FAU - Eskelinen, M AU - Eskelinen M FAU - Kosma, V-M AU - Kosma VM LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Cancer JT - European journal of cancer (Oxford, England : 1990) JID - 9005373 RN - 0 (DNA-Binding Proteins) RN - 0 (Ki-67 Antigen) RN - 0 (Neoplasm Proteins) RN - 0 (Transcription Factor AP-2) RN - 0 (Transcription Factors) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Analysis of Variance MH - Breast Neoplasms/*metabolism MH - Cell Division MH - DNA-Binding Proteins/*metabolism MH - Female MH - Follow-Up Studies MH - Humans MH - Immunohistochemistry/methods MH - Ki-67 Antigen/metabolism MH - Middle Aged MH - Neoplasm Proteins/*metabolism MH - Prognosis MH - Prospective Studies MH - Receptor, ErbB-2/*metabolism MH - Survival Analysis MH - Transcription Factor AP-2 MH - Transcription Factors/*metabolism EDAT- 2004/06/16 05:00 MHDA- 2004/08/25 05:00 CRDT- 2004/06/16 05:00 PHST- 2003/11/12 00:00 [received] PHST- 2004/02/13 00:00 [revised] PHST- 2004/02/25 00:00 [accepted] PHST- 2004/06/16 05:00 [pubmed] PHST- 2004/08/25 05:00 [medline] PHST- 2004/06/16 05:00 [entrez] AID - S095980490400214X [pii] AID - 10.1016/j.ejca.2004.02.020 [doi] PST - ppublish SO - Eur J Cancer. 2004 Jul;40(10):1485-95. doi: 10.1016/j.ejca.2004.02.020.