An immunostaining panel of C-reactive protein, N-cadherin, and S100 calcium binding protein P is useful for intrahepatic cholangiocarcinoma subtyping.

Abstract

This study aimed to establish an immunohistochemical panel useful for subclassification of intrahepatic cholangiocarcinoma (iCCA) into small- and large-duct types. Fifty surgical cases of iCCA consisting of small- (n = 31) and large-duct types (n = 19) were examined. To imitate liver needle biopsies, tissue microarrays were constructed using three tissue cores (2 mm in diameter) obtained from one representative paraffin block of each case. Immunostaining for C-reactive protein (CRP), N-cadherin, tubulin beta-III (TUBB3), neural cell adhesion molecule (NCAM), and S100 calcium binding protein P (S100P) was conducted. Most cases of small-duct iCCA were immunoreactive to CRP and N-cadherin, whereas expressions of these markers were markedly less common in large-duct iCCA (CRP, 97% vs. 5%, P < 0.001; N-cadherin, 87% vs. 16%, P < 0.001). TUBB3 and NCAM were also more frequently expressed in small-duct iCCA (65% vs. 32%, P = 0.006; 58% vs. 5%, P < 0.001), but their sensitivities were lower than those of CRP and N-cadherin. S100P was more commonly expressed in large-duct iCCA than in small-duct iCCA (95% vs. 29%, P < 0.001), and diffuse expressions were observed in 17 of 19 cases of large-duct iCCA (90%). All cases with a CRP+/S100P- immunophenotype were of small-duct type, whereas all but one case with a CRP-/S100P+ immunophenotype were of large-duct type. Of 10 cases with a double-positive or double-negative immunophenotype, 7 were appropriately classified based on immunoreactivity to N-cadherin. In conclusion, CRP, N-cadherin, and S100P form a useful immunohistochemical panel for iCCA subclassification, and correct subclassification was possible in 92% of cases based on a proposed, simple algorithm.

• Authors: Masayuki Akita, Ryuichiro Sawada, Masato Komatsu, Nadia Suleman, Tomoo Itoh, Tetsuo Ajiki, Nigel Heaton, Takumi Fukumoto, Yoh Zen
• Journal: Human pathology (Hum Pathol) Vol. 109 Pg. 45-52 (03 2021) ISSN: 1532-8392 [Electronic] United States
• PMID: 33321161 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Inc.

Chemical References

• Biomarkers, Tumor
• Cadherins
• Calcium-Binding Proteins
• Neoplasm Proteins
• S100P protein, human
• C-Reactive Protein

Topics

• Aged
• Aged, 80 and over
• Bile Duct Neoplasms (metabolism, pathology)
• Bile Ducts, Intrahepatic (metabolism, pathology)
• Biomarkers, Tumor (analysis)
• C-Reactive Protein (metabolism)
• Cadherins (metabolism)
• Calcium-Binding Proteins (metabolism)
• Cholangiocarcinoma (metabolism, pathology)
• Diagnosis, Differential
• Female
• Humans
• Immunophenotyping (methods)
• Liver Neoplasms (metabolism, pathology)
• Male
• Middle Aged
• Neoplasm Proteins (metabolism)