Variability In HER2 Expression Between Primary Colorectal Cancer And Corresponding Metastases

Background:Human epidermal growth factor receptor-2(HER2)served a function in tumorigenesis and development of several solid tumors and guided the choice of targeted drugs.Nevertheless,few data about the expression of HER2 in colorectal cancer(CRC)are available,let alone the evidence of the HER2 differential expression in primary lesion and matched metastases.Additionally,there are no agreement on the relationship between HER2 and the prognosis of CRC.Objective:This study aimed to investigate the HER2 status of primary colorectal cancer and corresponding metastases,and determine the correlation between HER2 and clinicopathological characteristics.Methods:We collected the clinicopathlogical features of 98 CRC patients and 66 patients which were previously evaluated for the KRAS status.The tissue samples of primary CRC tumors(n=98),noninvolved colorectal mucosa(n=98),paired lymph nodes(n=98),69 patients had positive metastatic nodes,and liver metastases(n=22)were evaluated using immunohistochemistry for HER2.The kappa test was used to evaluate the concordance rate of HER2 status.Survival analysis was established according to the Kaplan-Meier method.Results:HER2 overexpression was more common in primary tumors among the younger patients(P<0.05).No survival significance was revealed in the HER2 status.The HER2-positive rate was 11.2%for the primary CRC tumors,0%for the normal adjacent mucosa tissues,10.1%for the matched positive lymph nodes,and 31.8%for the corresponding metastasis.Seven of sixty-nine cases(10.1%)exhibited biomarker discordance in nodal metastases compared with primary tumors(κ=0.48,P<0.05);6 out of 22 cases(27.3%)exhibited biomarker discrepancy in liver metastases compared with primary tumors(κ=0.32,P>0.05).Compared with lymph nodes,HER2 overexpression in the primary tissue was more common in KRAS wild-type patients(P<0.05).Conclusions:The present study showed a high rate of discordance in matched pairs of primary tumors and metastases,suggesting that the accurate evaluation of HER2 status is essential before any therapeutic decision.