HER2 oncogene amplification, being accompanied by its overexpression, is an established driver event in breast and gastric carcinomas. The functional role of HER2 in pathogenesis of other tumor types is less defined.
2401 archival samples of lung carcinomas (LC) and 1969 samples of colorectal carcinomas (CRC) were subjected to HER2 copy number analysis. Selected tumors with amplification of this oncogene were further subjected to HER2 immunohistochemistry and mRNA quantitation. In addition, the expression levels of some neighbouring genes located in 17q12-21 amplicon were analyzed.
Frequency of HER2 amplification was similar in both groups, being 100/2401 (4.2%) in LC and 84/1969 (4.3%) in CRC, respectively. 10 (82%) out of 12 analyzed HER2-amplified CRCs demonstrated clear evidence for HER2 protein and mRNA overexpression, while this estimate approached to only 3 (27%) out of 11 for LCs. Expression analysis of GRB7, STARD3, and LASP1 revealed a statistically significant correlation between HER2 and STARD3 levels [r = 0.571, Spearman test]. High STARD3 expression was observed in HER2-amplified CRCs but not LCs [p = 0.03].
HER2 amplification is frequently accompanied by gene overexpression in colorectal but not lung adenocarcinomas. STARD3 gene belonging to 17q12-21 amplicon demonstrates evidence for activation in HER2-amplified colorectal neoplasms and therefore deserves further analysis.
Clinical trial identification
Legal entity responsible for the study
Russian Science Foundation.
All authors have declared no conflicts of interest.