Abstract
Background: The assessment of human epidermal growth factor receptor 2 (HER2) gene amplification is essential in order to identify those patients affected by advanced gastric cancer who may benefit from Trastuzumab targeted therapy. Materials and Methods: With the aim to investigate the concordance rate in HER2 status between primary gastric carcinoma (GC) and synchronous lymphnode metastases, we investigated HER2 status in a cohort of 108 surgical formalin-fixed paraffin-embedded specimens of GC and matched synchronous metastatic lymph nodes collected from three different units of Anatomic Pathology in southern of Italy. Fleiss-Cohen weighted k statistics were used to assess the concordance rate of HER2 status. Results: HER2 amplification was observed in 17% of primary GCs and the overall concordance rate with corresponding nodal metastases was 90.74%. Changes in HER2 status between primary GC and matched synchronous metastases were evidenced in 10 (9.26%) cases. Of these, 6 cases were HER2 amplified in the primary GC and not amplified in the metastases, while 4 were HER2 not amplified in the primary tumour and amplified in the lymph node metastases. Conclusions: Although at present the simultaneous determination of HER2 in advanced gastric cancer and corresponding metastatic lymph nodes is not mandatory, the possibility that the synchronous metastases of GC have a different HER2 status from that of the primary tumour is of remarkable significance; Indeed this may have influence on the therapeutic management and prognosis of the patients.
Highlights
Recent studies showed that the gene expression profile of breast and colorectal cancer may display significant variation among paired samples of primary tumours, disseminated neoplastic cells and patient metastases [1,2,3,4,5]
Histopathological diagnosis according to the World Health Organization (WHO) criteria was: Adenocarcinoma in 62 cases, poorly cohesive carcinoma in 35 and mixed in 11
Trastuzumab on the basis of human epidermal growth factor receptor 2 (HER2) positivity in the gastric carcinoma (GC) only, while our findings suggest that HER2 status should be assessed, in metachronous metastases, and in synchronous nodal metastases before treatment decision
Summary
Recent studies showed that the gene expression profile of breast and colorectal cancer may display significant variation among paired samples of primary tumours, disseminated neoplastic cells and patient metastases [1,2,3,4,5]. A significant discordance rate in human epidermal growth factor receptor (HER2) receptor status was retrospectively demonstrated between primary and recurrent/metastatic breast cancer [6,7,8,9,10]. This discrepancy may depend upon changes in HER2 receptor expression during the natural history of the tumour and has clinical and therapeutic relevance [11].
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