Impact of ADAM17 Expression as a Potential Prognostic Biomarker and Target for Therapy in Node-negative Breast Carcinoma

Abstract

Aims: To evaluate the expression and the possible prognostic impact of the tissue-based protein ADAM17 in node-negative breast cancer and investigate its association with clinical and pathological features to aid in differentiating indolent node-negative breast cancer from aggressive node-negative breast cancer. Study Design:  Cross sectional. Place and Duration of Study: Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, from December 2012 to June 2013. Methodology: 50 cases of breast cancer patients (40 node-negative and 10 node-positive) with ages ranging from 24 - 89 and with tumor size ranging from 0.6 cm to 4.7 cm were used. The ADAM17 protein expression was confirmed by immunohistochemistry analysis, which was performed on formalin-fixed, paraffin-embedded, 3 micro meters thick tissue sections using the avidin-biotin-peroxidase complex method. In addition, the presence of HER2, Ki67, Progesterone and Estrogen receptors were also determined. Results: Both node-negative and node-positive breast cancer showed ADAM17 expression with more expression in node-negative cases. The anti-ADAM17 antibodies showed immunostaining with 19 strong expression (38% - 19/50) and 31 weak expression (62% - 31/50) .In addition to ADAM17, other markers such as ER, PR, HER2 and Ki67 were also expressed. In analyzing the relationship between ADAM17 expression and clinicopathological parameters, the expression level did not present any statistical relationship with all the conventional prognostic factors with P value >0.05 except histological type with P value of .009 and .01. Conclusion: Our study shows ADAM17 protein expression may be involved in human breast cancer initiation, progression and distant metastasis and its prognostic impact could be independent of conventional prognostic factors. In grouping high expression against low, we had 19 high risks and 31 low risks. Upon further confirmation, ADAM17 could be used to determine individuals who may need adjuvant chemotherapy and those who could be spared from the toxic effect of chemotherapy.