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

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.