An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas

Takahiro Yoshizawa; Takeshi Uehara; Mai Iwaya; Tomoyuki Nakajima; Akira Shimizu; Koji Kubota; Tsuyoshi Notake; Noriyuki Kitagawa; Hitoshi Masuo; Hiroki Sakai; Hikaru Hayashi; Hidenori Tomida; Shiori Yamazaki; Shohei Hirano; Hiroyoshi Ota; Yuji Soejima

doi:10.1097/PAS.0000000000002224

An Immunohistochemical Analysis of Osteopontin and S100 Calcium-binding Protein P is Useful for Subclassifying Large- and Small-duct Type Intrahepatic Cholangiocarcinomas

Am J Surg Pathol. 2024 Apr 8. doi: 10.1097/PAS.0000000000002224. Online ahead of print.

Authors

Takahiro Yoshizawa^{1

2}, Takeshi Uehara², Mai Iwaya², Tomoyuki Nakajima², Akira Shimizu¹, Koji Kubota¹, Tsuyoshi Notake¹, Noriyuki Kitagawa¹, Hitoshi Masuo¹, Hiroki Sakai¹, Hikaru Hayashi¹, Hidenori Tomida¹, Shiori Yamazaki¹, Shohei Hirano¹, Hiroyoshi Ota^{2

3}, Yuji Soejima¹

Affiliations

¹ Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto Japan.
² Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.
³ Department of Biomedical Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan.

PMID: 38584480
DOI: 10.1097/PAS.0000000000002224

Abstract

Intrahepatic cholangiocarcinoma (iCCA) has been newly subclassified into two different subtypes: large-duct (LD) type and small-duct (SD) type. However, many cases are difficult to subclassify, and there is no consensus regarding subclassification criteria. LD type expresses the highly sensitive diagnostic marker S100 calcium-binding protein P (S100P), while SD type lacks sensitive markers. We identified osteopontin (OPN) as a highly sensitive marker for SD type. This study aimed to develop new subclassification criteria for LD-type and SD-type iCCA. We retrospectively investigated 74 patients with iCCA and subclassified them based on whole-section immunostaining of S100P and OPN. Of the 74 cases, 41 were subclassified as LD type, 32 as SD type, and one was indeterminate. Notably, all S100P-negative cases had OPN positivity. Seventy-three of the 74 cases (98.6%) were clearly and easily subclassified as LD or SD type using only these 2 markers. We also determined the value of immunohistochemistry in cases that were difficult to diagnose based on hematoxylin-eosin and Alcian blue-periodic acid-Schiff staining. Furthermore, we analyzed the clinicopathological characteristics and prognoses of these 2 subtypes. LD type was a poor prognostic factor on univariate analysis; it had significantly worse overall survival (P= 0.007) and recurrence-free survival (P < 0.001) than the SD type. In conclusion, we propose new subclassification criteria for iCCA based on immunostaining of S100P and OPN. These criteria may help pathologists to diagnose subtypes of iCCA, supporting future clinical trials and the development of medications for these 2 subtypes as distinct cancers.