Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Apr 25;13(9):1542.
doi: 10.3390/diagnostics13091542.

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value

Lavinia Patricia Mocan  1 , Ioana Rusu  2 , Carmen Stanca Melincovici  1 , Bianca Adina Boșca  1 , Tudor Mocan  3   4 , Rareș Crăciun  4   5 , Zeno Spârchez  4   5 , Maria Iacobescu  6 , Carmen Mihaela Mihu  1
Affiliations

The Role of Immunohistochemistry in the Differential Diagnosis between Intrahepatic Cholangiocarcinoma, Hepatocellular Carcinoma and Liver Metastasis, as Well as Its Prognostic Value

Lavinia Patricia Mocan et al. Diagnostics (Basel). .

Abstract

Intrahepatic cholangiocarcinoma (iCCA) is the second most frequent primary hepatic malignant tumor, after hepatocellular carcinoma (HCC). Its incidence has risen worldwide, yet the only potentially curative treatment, surgical resection, is seldom applicable, and the median overall survival remains extremely low. So far, there are no personalized therapy regimens. This study investigated whether routine immunohistochemical stains have diagnostic and/or prognostic value in iCCA. Clinical, imaging, and pathology data were retrospectively gathered for patients diagnosed with iCCA, HCC, or liver metastases assessed using liver needle biopsies. Three study groups with an equal number of cases (n = 65) were formed. In the iCCA group, CK19, CA19-9, CK7, and CEA demonstrated the highest sensitivities (100%, 100%, 93.7%, and 82.6%, respectively). The most relevant stains used for diagnosing HCCs were Glypican 3, CD34 (sinusoidal pattern), and Hep Par 1, with corresponding sensitivities of 100%, 100%, and 98.2%. The immunohistochemical panels for diagnosing metastatic tumors were chosen after correlating the clinical data and morphologic H&E aspects. Moderate/intensely positive CK7 expression and absent/low amount of intratumoral immune cells were favorable prognostic factors and correlated with increased overall survival in both the univariate analysis and the multivariate regression adjusted for age, existence of cirrhosis, number of tumors, and tumor differentiation.

Keywords: CK7; hepatocellular carcinoma; immunohistochemistry; intrahepatic cholangiocarcinoma; intratumoral immune cells; needle biopsy; secondary tumor.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Kaplan–Meier survival analysis regarding the pathology-confirmed diagnosis of intrahepatic cholangiocarcinoma (iCCA) versus hepatocellular carcinoma (HCC); p < 0.001 (log-rank test).
Figure 2
Figure 2
Kaplan–Meier survival analysis for intrahepatic cholangiocarcinoma (iCCA) cases, regarding CK7 immunoexpression.
Figure 3
Figure 3
Kaplan–Meier survival analysis for intrahepatic cholangiocarcinoma (iCCA) cases based on the amount of intratumoral immune cells.
See this image and copyright information in PMC

References

    1. Shaib Y., El-Serag H. The Epidemiology of Cholangiocarcinoma. Semin. Liver Dis. 2004;24:115–125. doi: 10.1055/s-2004-828889. - DOI - PubMed
    1. WHO Classification of Tumours Editorial Board . Digestive System Tumours, WHO Classification of Tumours. 5th ed. World Health Organization; Lyon, France: IARC Publications; Lyon, France: 2019.
    1. Saha S.K., Zhu A.X., Fuchs C.S., Brooks G.A. Forty-Year Trends in Cholangiocarcinoma Incidence in the U.S.: Intrahepatic Disease on the Rise. Oncologist. 2016;21:594–599. doi: 10.1634/theoncologist.2015-0446. - DOI - PMC - PubMed
    1. Mukkamalla S.K.R., Naseri H.M., Kim B.M., Katz S.C., Armenio V.A. Trends in Incidence and Factors Affecting Survival of Patients with Cholangiocarcinoma in the United States. J. Natl. Compr. Cancer Netw. 2018;16:370–376. doi: 10.6004/jnccn.2017.7056. - DOI - PubMed
    1. Tyson G.L., El-Serag H.B. Risk Factors for Cholangiocarcinoma. Hepatology. 2011;54:173–184. doi: 10.1002/hep.24351. - DOI - PMC - PubMed