Short abstract
This letter to the editor remarks on the topic of HER2 expression as a potential target of adjuvant therapy for biliary tract cancer, focusing on patients with intrahepatic cholangiocarcinoma.
With great interest, we read the manuscript by Vivaldi et al. entitled “HER2 Overexpression as a Poor Prognostic Determinant in Resected Biliary Tract Cancer” [1] in the recent issue of The Oncologist. This study demonstrated that HER2 overexpression was associated with poorer disease‐free survival in 100 patients with resected biliary tract cancer (BTC), and the authors asserted that HER2 expression could be a potential target of adjuvant therapy. Although the authors should be congratulated on a substantial effort and this manuscript provides significant clinical impact in the field of BTC, we wish to discuss this topic focusing on patients with intrahepatic cholangiocarcinoma (ICC).
First, the proportion of HER2 overexpression in patients with BTC may be different according to anatomical site on the basis of recent genomic analyses [2]. Especially, HER2 overexpression seems to be rare (a recent systematic review reported a mean HER2 overexpression rate of 4.8% [3]) in patients with ICC compared with the other BTCs, although the present study included four patients with HER2‐overexpressing ICC (12.5%). In this context, we analyzed 51 patients with ICC who underwent R0/R1 resection between 2009 and 2017 in our institution. HER2 expression was evaluated using gastric criteria [4] by two dedicated pathologists (S.M. and H.H.). Contrary to the present study, no patients had HER2 overexpression in our study population (Fig. 1). Considering our findings and previous series, the proportion of HER2 overexpression in patients with resected ICC may be very low, and the reproducibility of the prognostic impact of HER2 overexpression may be limited in these patients.
Figure 1.
Examples of HER2 immunohistochemistry (IHC) staining. (A): Score 1+. (B): Score 0. Of the 51 samples, two samples had score 1, and 49 samples had score 0. IHC in HER2 was performed using rabbit anti‐ErbB2 antibody (ab214275, Abcam plc, Cambridge, U.K.) at 1:400 dilutions, and staining was done with an automated staining machine (Ventana Discovery Ultra, Roche Diagnostics, Tokyo, Japan).
Second, surgical procedures in patients with BTC are considerably different (e.g., hepatectomy or pancreaticoduodenectomy) according to anatomical site, and corresponding morbidity may be varied [5]. Furthermore, omission of lymphadenectomy seems to be an ICC‐specific topic considering the surgical anatomy [6], although the authors included this factor in the overall study population. Considering the possible prognostic impact of surgical complications or implementation of lymphadenectomy in patients with resected ICC [7, 8], the impact of HER2 expression on patients with resected BTC should be analyzed separately by anatomical site. The present study attempted to compensate for this topic by using multivariate analysis; however, small sample size might influence statistical validity. Meanwhile, both ICC and HER2 overexpression were associated with poor disease‐free survival in the present study; their interaction suggested that prognostic impact of HER2 overexpression in patients with resected ICC was limited.
In conclusion, the present study by Vivaldi et al. does provide clinical impact regarding the possible role of HER2 overexpression as a negative prognostic factor in resected BTC. Difference of genetic profiles of BTC or surgical procedures according to anatomical site may require further studies with much larger sample size, which may lead to a better understanding clinical significance of HER2 overexpression in resected BTC.
Disclosures
The authors indicated no financial relationships.
Acknowledgments
This letter was supported by Public Interest Incorporated Foundation, The Kyoto University Foundation.
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