Changes in human epidermal growth factor receptor 2 status between primary breast/gastric carcinomas and synchronous metastatic lymph nodes: how can we explain them?

Ieni A, Barresi V, Branca G, Licata L, Caruso RA, Tuccari G. Changes in human ep

Antonio Ieni, Valeria Barresi, Giovanni Branca, Lu

Department of Human Pathology "Gaetano Barresi", U

2015

21-26

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Aim: Previous studies demonstrated discordant expression of human epidermal growth-factor receptor 2 (HER2) between primary cancer and their recurrence/metastasis. This study further evaluated HER2 status between primary gastric and breast invasive carcinomas and paired metastatic disease to lymph nodes. Methods: This study collected formalin-fixed paraffin-embedded representative tissue blocks from 62 gastric and 65 breast primary carcinomas as well as synchronous metastatic lymph nodes (male:female = 39:88; age ranged between 44 and 95 years with mean age of 69.32 years) for immunohistochemical staining of HER2 expression (DAKO HercepTest™ kit). If immunohistochemical HER2 score reached to 2+, HER2 amplification was then assessed using fluorescence in situ hybridization (PharmDx™ kit DAKO). Results: The discordant HER2 pooled rate, regardless either negative or positive conversion, was 9.67% in primary gastric carcinoma and corresponding nodal metastasis, while the changes in HER2 expression were revealed in 4.61% of mammary and lymph node neoplastic samples. A high-level concordance in HER2 expression between primary carcinoma and synchronous metastatic lymph nodes was confirmed in both types of cancer; the observed event of discordant HER2 status should be ascribed to intra-tumor heterogeneity, mostly appreciable in gastric cancer. Conclusion: In any case, the shift from positive to negative HER2 expression suggests that trastuzumab could be the targeted treatment choice whereas the opposite shift should be evaluated by a simultaneous HER2 determination in both primary and metastatic lymph nodes.