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

journal article Apr 08, 2024

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

American Journal of Surgical Pathology Vol. 48 No. 6 pp. 751-760 · Ovid Technologies (Wolters Kluwer Health)

View at Publisher Save 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.

Topics

No keywords indexed for this article. Browse by subject →

References

29

[1]

Blechacz "Clinical diagnosis and staging of cholangiocarcinoma" Nat Rev Gastroenterol Hepatol (2011) 10.1038/nrgastro.2011.131

[2]

Razumilava "Cholangiocarcinoma" Lancet (2014) 10.1016/s0140-6736(13)61903-0

[3]

Bertuccio "Global trends in mortality from intrahepatic and extrahepatic cholangiocarcinoma" J Hepatol (2019) 10.1016/j.jhep.2019.03.013

[4]

Florio "Global trends in intrahepatic and extrahepatic cholangiocarcinoma incidence from 1993 to 2012" Cancer (2020) 10.1002/cncr.32803

[5]

Sirica "Intrahepatic cholangiocarcinoma: Continuing challenges and translational advances" Hepatology (2019) 10.1002/hep.30289

[6]

Marin "Current and novel therapeutic opportunities for systemic therapy in biliary cancer" Br J Cancer (2020) 10.1038/s41416-020-0987-3

[7]

Wirth "Surveillance in cholangiocellular carcinoma" Best Pract Res Clin Gastroenterol (2016) 10.1016/j.bpg.2016.11.001

[8]

Mavros "Treatment and prognosis for patients with intrahepatic cholangiocarcinoma: Systematic review and meta-analysis" JAMA Surg (2014) 10.1001/jamasurg.2013.5137

[9]

The 2019 WHO classification of tumours of the digestive system

Iris D Nagtegaal, Robert D Odze, David Klimstra et al.

Histopathology 2020 10.1111/his.13975

[10]

Aishima "Pathogenesis and classification of intrahepatic cholangiocarcinoma: Different characters of perihilar large duct type versus peripheral small duct type" J Hepatobiliary Pancreat Sci (2015) 10.1002/jhbp.154

[11]

Akita "Dichotomy in intrahepatic cholangiocarcinomas based on histologic similarities to hilar cholangiocarcinomas" Mod Pathol (2017) 10.1038/modpathol.2017.22

[12]

Komuta "Clinicopathological study on cholangiolocellular carcinoma suggesting hepatic progenitor cell origin" Hepatology (2008) 10.1002/hep.22238

[13]

Liau "Morphological subclassification of intrahepatic cholangiocarcinoma: Etiological, clinicopathological, and molecular features" Mod Pathol (2014) 10.1038/modpathol.2013.241

[14]

Kendall "Anatomical, histomorphological and molecular classification of cholangiocarcinoma" Liver Int (2019) 10.1111/liv.14093

[15]

Akita "Histological and molecular characterization of intrahepatic bile duct cancers suggests an expanded definition of perihilar cholangiocarcinoma" HPB (Oxford) (2019) 10.1016/j.hpb.2018.07.021

[16]

Banales "Cholangiocarcinoma 2020: The next horizon in mechanisms and management" Nat Rev Gastroenterol Hepatol (2020) 10.1038/s41575-020-0310-z

[17]

Hayashi "Distinct clinicopathologic and genetic features of 2 histologic subtypes of intrahepatic cholangiocarcinoma" Am J Surg Pathol (2016) 10.1097/pas.0000000000000670

[18]

Song "Single-cell transcriptomic analysis suggests two molecularly subtypes of intrahepatic cholangiocarcinoma" Nat Commun (2022) 10.1038/s41467-022-29164-0

[19]

Franzén "Isolation and characterization of two sialoproteins present only in bone calcified matrix" Biochem J (1985) 10.1042/bj2320715

[20]

Subraman "OPN -Revisited" J Clin Diagn Res (2015)

[21]

Anborgh "Pre- and post-translational regulation of osteopontin in cancer" J Cell Commun Signal (2011) 10.1007/s12079-011-0130-6

[22]

Agrawal "Osteopontin identified as colon cancer tumor progression marker" C R Biol (2003) 10.1016/j.crvi.2003.09.007

[23]

Lin "Overexpression of osteopontin in hepatocellular carcinoma and its relationships with metastasis, invasion of tumor cells" Mol Biol Rep (2011) 10.1007/s11033-010-0671-4

[24]

Loosen "Elevated levels of circulating osteopontin are associated with a poor survival after resection of cholangiocarcinoma" J Hepatol (2017) 10.1016/j.jhep.2017.06.020

[25]

Nakajima "Osteopontin expression in the invasive front stroma of colorectal adenocarcinoma is associated with tumor budding and prognosis" Pathol Res Pract (2022) 10.1016/j.prp.2022.154190

[26]

Hass "Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis" World J Gastroenterol (2008) 10.3748/wjg.14.2501

[27]

Akita "An immunostaining panel of C-reactive protein, N-cadherin, and S100 calcium binding protein P is useful for intrahepatic cholangiocarcinoma subtyping" Hum Pathol (2021) 10.1016/j.humpath.2020.12.005

[28]

Ma "Single-cell atlas of tumor cell evolution in response to therapy in hepatocellular carcinoma and intrahepatic cholangiocarcinoma" J Hepatol (2021) 10.1016/j.jhep.2021.06.028

[29]

Zen "Intrahepatic cholangiocarcinoma: typical features, uncommon variants, and controversial related entities" Hum Pathol (2023) 10.1016/j.humpath.2022.06.001

Metrics

8

Citations

29

References

Details

Published: Apr 08, 2024
Vol/Issue: 48(6)
Pages: 751-760

Authors

T

Takahiro Yoshizawa

Department of Surgery, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Shinshu University School of Medicine, Matsumoto Japan; Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

T

Takeshi Uehara

Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

M

Mai Iwaya

Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

T

Tomoyuki Nakajima

Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan

A

Akira Shimizu