Eкспресија на рецепторите ЕР, ПР и ХЕР-2 кај примарен карцином на дојка и кај метастази на лимфните аксиларни јазли

Abstract

Introduction: Breast cancer is described as heterogenic, changing, disease, from clinical and pathological point of view, as well as from different responses to treatment and prognosis. Traditional biomarkers as Estrogen receptors (ER) and Progesteron receptors (PR) are not only clinical prognostic factors, but they have also significant role in selection of patients who would benefit from endocrine treatment. Lately, HER2/neu has been reported not only as prognostic factor, but as well as responsible indicator for treatment targeting this receptor. Ki-67 is cell proliferation biomarker which has been reported not only as prognostic factor, but also as important marker for application of adjuvant treatment. Important factor for determination of treatment strategy is presence of metastasis, especially in regional lymph nodes. These days it is important to examine the molecular profile of metastasis, noticing that a number of data are showing instability of receptors in tumor cells during the metastatic process. Aim: To review hormonal receptors (ER and PR), Her2/neu and Ki-67 with immunohistochemical methods at invasive breast cancer, to evaluate its relation with stage of tumor differentiation and to determine expression of ER, PR, Her-2/neu and Ki-67 between primary tumor and its metastasis in axillary lymph nodes. Designe: This is retrospective-prospective study. Materials and methods: There were 64 subjects includes in the study, patients with invasive breast cancer and with metastasis in axillary lymph nodes. Subjects included in the study have undergone radical mastectomy and axillary dissection. None of patients selected for the study have undergone prior treatment. The study has been approved by the Ethical Committee of University and Clinical Centre of Kosovo. Immunohistochemistry has been implemented manually, which was conducted with paraffin blocs and samples from new patients. Immunohistochemistry for ER, PR, Her2/neu and Ki-67 receptors has been conducted based on producer’s instructions (En vision+, DAKO Denmark). Results: Majority of tumors were of grade 2 (64%), and the rest of tumors (26%) included in the study were of the grade 3. Our results showed that there is significant correlation between ER expression and grade of primary tumor differentiation, while ER expression in axillary lymph nodes didn’t show significance with grade of tumor differentiation. Correlation between PR of primary tumor with grade of tumor differentiation was not shown to be significant, while moderate and low differentiated tumors had similar expression with of PR in metastatic axillary lymph nodes. Expression of Her2/neu did not show significant difference between grade of primary tumor differentiation and with axillary lymph nodes. Index of proliferation measured between Ki-67 from primary breast cancer and grade of tumor differentiation showed statistical significance. Positive statistical significance were found between Ki-67 marker and grade of tumor differentiation in axillary lymph nodes. The degree of matching of ER between primary tumor and axillary metastasis was 70.3%, for PR was 64.1%, for Her2/neu marker was 75% and degree of matching for Ki-67 expression in our study was 73.4%. Conclusion: In the primary tumor ER and PR overexpression is seen at high frequency at grade 2 tumor compared to Her2/neu overexpression where tumor grade 2 and 3 are seen equally with 50%. Her2/neu expression in primary tumors and metastatic lymph nodes decreases with increasing expression of estrogenic and progesterone receptors and vice versa. The Ki-67 receptor in primary tumor is directly related to the degree tumor differentiation. There is direct concordance in expression of ER and PR between primary breast cancer and metastasis in axillary lymph nodes. Frequent expression of Her2/neu proto-oncogene in metastatic axillary lymph nodes in relation to the primary tumor has been confirmed as statistically significant. There is direct concordance in frequency of Ki-67 proliferation between primary invasive ductal carcinoma and metastasis in axillary lymph nodes.