Discordance rate of HER2 status in primary breast carcinomas versus synchronous axillary lymph node metastases: a multicenter retrospective investigation

Abstract

Antonio Ieni,1 Valeria Barresi,1 Rosario Caltabiano,2 Anna Maria Cascone,3 Rachele Del Sordo,4 Daniela Cabibi,5 Pio Zeppa,3 Salvatore Lanzafame,2 Angelo Sidoni,4 Vito Franco,5 Giovanni Tuccari1 1Department of Human Pathology Gaetano Barresi, Section of Anatomic Pathology, University of Messina, Messina, 2Department GF Ingrassia, Section of Anatomic Pathology, University of Catania, Catania, 3Department of Medicine and Surgery, University of Salerno, Salerno, 4Institute of Pathologic Anatomy and Histology, Division of Cancer Research, University of Perugia, Perugia, 5Department of Human Pathology, Section of Anatomic Pathology, University of Palermo, Palermo, Italy Background: Human epidermal growth factor receptor 2 (HER2) is considered to be a therapeutic and prognostic marker in the management of breast carcinoma (BC), although discordance rates between primary and metastatic or locally recurrent lesions have been reported. Methods: One hundred and forty-eight paraffin-embedded BC tissues from patients of mean age 59.27 (33–96) years and corresponding synchronous lymph node metastases were collected and retrospectively studied using immunohistochemistry and fluorescence in situ hybridization to evaluate HER2 status. Fleiss-Cohen weighted k statistics were used to assess the concordance rate between HER2 status of the primary BC and the synchronous metastatic lesions. Results: The overall concordance rate for HER2 was 95.28%. Eighty-nine cases were concordantly HER2-negative in primary BC and nodal metastases, and 52 cases were HER2-positive in both primary and metastatic tumors. Changes in HER2 status between primary BC and corresponding synchronous metastases were observed in seven (4.72%) cases. Three of the discordant cases were HER2-negative in the primary tumor and HER2-positive in the metastases, while four cases were HER2-positive in the primary BC and HER2-negative in the metastases. No significant correlations were identified between HER2 status and expression of hormone receptors, growth fraction (Ki-67), or other histopathological parameters (pT, pN, grade). Conclusion: Simultaneous determination of HER2 in BC and corresponding metastatic lymph nodes is not mandatory, but may strongly influence the therapeutic management. It was demonstrated that loss of HER2 amplification results in worse post-relapse survival and overall survival in BC patients and, on the other hand, a gain in HER2 expression in metastatic lymph nodes of BC may allow the possibility of a targeted treatment. Thus, our opinion is that significant prognostic information may be obtained by simultaneous assessment of HER2 status in both primary and synchronous metastatic BC. Keywords: human epidermal growth factor receptor 2, breast cancer, synchronous lymph nodes, metastases, prognosis