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Expression of HER2 and its association with AP-2 in breast cancer
Ist Teil von
European journal of cancer (1990), 2004-07, Vol.40 (10), p.1485-1495
Ort / Verlag
Oxford: Elsevier Ltd
Erscheinungsjahr
2004
Quelle
Access via ScienceDirect (Elsevier)
Beschreibungen/Notizen
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.