Association between the expression of hormone receptors, Her-2eu overexpression and tumor characteristics in women with primary breast cancer

摘要

Her-2eu overexpression has been correlated with poor prognostic tumors.The association between breast tumor characteristics and expression of ER, PR, Her-2eu overexpression, patient's age, tumor size, type and grade were retrospectively evaluated in 226 primary breast cancer referred to Armin pathobiology laboratory in 2005.We found that 21.7% of cases had HER-2eu overexpression. HER-2eu overexpression in ER negative cases(28.4%) was higher than ER positive cases(18.4%) and HER-2eu overexpression in PR negative cases(28.4%) was higher than PR positive cases(18.0%). The frequency of HER-2eu overexpression decreased from ER-PR- to ER+PR+(30.7% to 18.8%).The frequency of HER-2eu overexpression decreased significantly(P<0.05) from ER-PR- to ER+PR+(45.5% to 20.5%) in low grade tumors and HER-2eu overexpression decreased from ER-PR- to ER+PR+(18.8% to 15.4%) in high grade tumors but this difference was not significant(P=0.790).Our results revealed higher proportion of ER- and PR- tumors associated with HER-2eu overexpression, also younger patients have higher rate of HER-2eu overexpression. Introduction The HER-2eu(c-erbB-2) is an oncogene that encodes a transmembrane glycoprotein with tyrosin kinase activity known as p185, which belongs to the family of epidermal growth factor receptor [12]. Cells transfected with HER-2eu acquire a more malignant phenotype? with stimulation of cell proliferation? invasion and metastasis. This has been confirmed in the clinic: women with Her-2eu positive breast cancer have a worse prognosis than those with Her-2eu negative cancer [134]. although Her-2eu overexpression has been correlated with poor prognostic tumor characteristics such as higher histological grade? S phase fraction? increased tumor size? increased number of involved lymph nodes? absence of lobular histology and negative or lower Estrogen receptor (ER) expression [15] but its role as an independent prognostic factor is not significant in multivariate analysis [16]. Semiquantitative measurement using immunohistochemistery (IHC) for the Her-2eu membrane receptor protein can accurately predict gene amplification [7].Estrogen receptor (ER) correlates inversely with the presence of epidermal growth factor receptor [1] also it has been suggested that there is an inverse relation between the expression of the progesterone receptor (PR) and Her-2eu in women with ER+ breast cancer [58]. The aim of this study was to determine the relation between Her-2eu overexpression and other clinicopathological factors in women with operable breast cancer. Materials and methods The association between breast tumor characteristics and expression of ER, PR? Her-2eu overexpression, patient’s age, largest tumor size, tumor type and tumor grade were retrospectively evaluated in 226 women with primary breast cancer referred to Armin pathobiology laboratory in 1384. The evaluation of histopathologic characteristics was carried out on paraffin –embedded tissue blocks which were stained with Hematoxylin & Eosin. The Immunohistochemistry staining for ER, PR and Her-2eu were done on paraffin-embedded tissue blocks according to the envision method using primary monoclonal antibodies ( Dako Kits).The DAKO scoring system for Her-2eu was defined as negative for scores 0 &1+ and positive for score 2+ & 3+ and overexpression for score 3+ (Table1)[1]. Using the H score for ER and PR? a negative result was defined as a score of ≤50? weakly positive as 51-100? moderately positive as 101-200 and strongly positive as >200. Tumor grading was performed according to Richardson & Bloom grading system [1].In a univariate analysis the association between ER, PR and Her-2eu was evaluated and the chi square test was used to examine the categorical variables and the association between ER, PR expression and other clinicopathologic variables. The results were considered statistically significant if the P value was < 0.05. All analysis were perfo