Heterogeneity of antigenic constellation in human hepatocellular carcinoma

Ceausu,Mihai; Socea,Bogdan; Serban,Dragos; Smarandache,Cătălin   Gabriel; Predescu,Dragoş; Bacalbaşa,Nicolae; Slavu,Iulian; Tulin,Adrian; Alecu,Lucian; Ceauşu,Zenaida

doi:10.3892/etm.2021.9701

Heterogeneity of antigenic constellation in human hepatocellular carcinoma

Authors:
- Mihai Ceausu
- Bogdan Socea
- Dragos Serban
- Cătălin Gabriel Smarandache
- Dragoş Predescu
- Nicolae Bacalbaşa
- Iulian Slavu
- Adrian Tulin
- Lucian Alecu
- Zenaida Ceauşu
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Affiliations: Department of Pathology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Surgery, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Obstetrics and Gynecology, ‘Carol Davila’ University of Medicine and Pharmacy, 020021 Bucharest, Romania, Department of Surgery, ‘Prof. Dr. Agrippa Ionescu’ Clinical Emergency Hospital, 011356 Bucharest, Romania, Pathology Department, ‘Sf. Pantelimon’ Emergency Hospital, 021659 Bucharest, Romania
Published online on: January 25, 2021 https://doi.org/10.3892/etm.2021.9701
Article Number: 270

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Abstract

Hepatocellular carcinoma is one of the primary liver malignancies responsible for over a million deaths per year worldwide (approximately 10% of all deaths in the adult age range). The diagnosis of HCC can be difficult and often requires the use of more than one microscopic technique. A retrospective study was performed on a study batch of 42 cases that died of HCC due to metastasis or other secondary complications. Tissue samples were taken in order to investigate the tumour antigenic constellation by means of IHC method using a large variety of antibodies. In situ hybridization was also performed for albumin mRNA to assess the albumin expression in some selected cases. Telomerase activity was investigated using IHC method for the hTERT catalytic subunit. A cocktail of hepatic cytokeratins (CK8, 18) combined with Hep Par‑1 and associated to albumin proved to be more powerful than albumin alone in differentiating HCC and increased the value of tumour diagnosis. hTERT expression was proportionally reverse to the tumour degree of differentiation, but was independent from the expression of tumour‑proliferating indexes. The heterogeneity of the antigenic constellation in hepatocellular carcinoma suggests an antigenic mosaicism, which can be expressed a synchronous or metachronous manner, depending on the tumour degree of differentiation.

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1	Jiang Y, Han QJ and Zhang J: Hepatocellular carcinoma: Mechanisms of progression and immunotherapy. World J Gastroenterol. 25:3151–3167. 2019.PubMed/NCBI View Article : Google Scholar
2	Amarapurkar AD, Rege JD, Joshi AS, Vaiphei K and Amarapurkar DN: Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors. Indian J Pathol Microbiol. 49:341–344. 2006.PubMed/NCBI
3	Negrut N, Khan SA, Bungau S, Zaha DC, Aron CR, Bratu O, Diaconu CC and Ionita-Radu F: Diagnostic challenges in gastrointestinal infections. Rom J Mil Med. 123:83–90. 2020.
4	Draghici T, Negreanu L, Bratu OG, Stoian AP, Socea B, Neagu TP, Stanescu AM, Manuc D and Diaconu CC: Paraneoplastic syndromes in digestive tumors: A review. Rom Biotechnol Lett. 24:813–819. 2019.
5	Quaglia A: Hepatocellular carcinoma: A review of diagnostic challenges for the pathologist. J Hepatocell Carcinoma. 5:99–108. 2018.PubMed/NCBI View Article : Google Scholar
6	Lai YS, Cheng CC, Lee MT, Chao WT, Lai YC, Hsu YH and Liu YH: The prognostic value of cytokeratin and sal-like protein 4 expression in hepatocellular carcinoma and intra-hepatic cholangiocarcinoma in Taiwan. Int J Med Sci. 15:1746–1756. 2018.PubMed/NCBI View Article : Google Scholar
7	Ferrell LD: Hepatocellular carcinoma and its variants. In: Odze and Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract, and Pancreas. 3rd edition. Elsevier Saunders Publishing House, pp1549-1557, 2015.
8	Torbenson MS, Ng IOL, Park YN, Roncalli M and Sakamoto M: Hepatocellular carcinoma, chapter 8: Tumours of tumours of the liver and intrahepatic bile ducts. In: WHO Classification of Tumours, Digestive System. 5th edition, pp229-239, 2019.
9	Kutlesic C, Katic V, Veliekovic L and Katic K: Atypical adenomatous hyperplasia in liver cirrhosis. Arch Oncol. 12 (Suppl 1):S10–S11. 2004.
10	Shafizadeh N and Kakar S: Diagnosis of well-differentiated hepatocellular lesions: role of immunohistochemistry and other ancillary techniques. Adv Anat Pathol. 18:438–445. 2011.
11	Epîngeac ME, Găman MA, Diaconu CC, Gad M and Găman AM: The evaluation of oxidative stress in obesity. Rev Chim (Bucharest). 70:2241–2244. 2019.
12	Dumitru N, Cocolos A, Caragheorgheopol A, Dumitrache C, Bratu OG, Neagu TP, Diaconu CC and Ghemigian A: Collagen-the ultrastructural element of the bone matrix. Rev Chim (Bucharest). 69:1706–1709. 2018.
13	Van Eyken P, Sciot R, Paterson A, Callea F, Kew MC and Desmet VJ: Cytokeratin expression in hepatocellular carcinoma: An immunohistochemical study. Hum Pathol. 19:562–568. 1988.PubMed/NCBI View Article : Google Scholar
14	Witjes CD, ten Kate FJ, Verhoef C, de Man RA and Jzermans JN: Immunohistochemical characteristics of hepatocellular carcinoma in non-cirrhotic livers. J Clin Pathol. 66:687–691. 2013.PubMed/NCBI View Article : Google Scholar
15	Fan Z, van de Rijn M, Montgomery K and Rouse RV: Hep Par 1 antibody stain for the differential diagnosis of hepatocellular carcinoma: 676 tumors tested using tissue microarrays and conventional tissue sections. Mod Pathol. 16:137–144. 2003.PubMed/NCBI View Article : Google Scholar
16	Hanif R and Mansoor S: Hep par-1: A novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma. J Coll Physicians Surg Pak. 24:186–189. 2014.PubMed/NCBI
17	Kakar S, Gown AM, Goodman ZD and Ferrell LD: Best practices in diagnostic immunohistochemistry: Hepatocellular carcinoma versus metastatic neoplasms. Arch Pathol Lab Med. 131:1648–1654. 2007.PubMed/NCBI View Article : Google Scholar
18	Wang XY, Degos F, Dubois S, Tessiore S, Allegretta M, Guttmann RD, Jothy S, Belghiti J, Bedossa P and Paradis V: Glypican-3 expression in hepatocellular tumors: Diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Hum Pathol. 37:1435–1441. 2006.PubMed/NCBI View Article : Google Scholar
19	DU JL, Wei LX and Wang YL: Expression and clinicopathologic significance of GPC3 and other antibodies in well-differentiated hepatocellular carcinoma. Zhonghua Bing Li Xue Za Zhi. 40:11–16. 2011.PubMed/NCBI(In Chinese).
20	Coston WM, Loera S, Lau SK, Ishizawa S, Jiang Z, Wu CL, Yen Y, Weiss LM and Chu PG: Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 32:433–444. 2008.PubMed/NCBI View Article : Google Scholar
21	Suceveanu AI, Stoian AP, Mazilu L, Voinea F, Hainarosie R, Diaconu CC, Pituru S, Nitipir C, Badiu DC, Ceausu I and Suceveanu AP: Interferon-free therapy is not a trigger for hepatocellular carcinoma in patients with chronic infection with hepatitis C virus. Farmacia. 66:904–908. 2018.PubMed/NCBI View Article : Google Scholar
22	Gheorghe G, Pantea Stoian A, Gaman MA, Socea B, Neagu TP, Stanescu AMA, Bratu OG, Mischianu DLD, Suceveanu AI and Diaconu CC: The benefits and risks of antioxidant treatment in liver diseases. Rev Chim (Bucharest). 70:651–655. 2019.
23	Segatelli V, de Oliveira EC, Boin IF, Ataide EC and Escanhoela CA: Evaluation and comparison of microvessel density using the markers CD34 and CD105 in regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Hepatol Int. 8:260–265. 2014.PubMed/NCBI View Article : Google Scholar
24	Lau SK, Prakash S, Geller SA and Alsabeh R: Comparative immunohistochemical profile of hepatocellular carcinoma, cholangiocarcinoma, and metastatic adenocarcinoma. Hum Pathol. 33:1175–1181. 2002.PubMed/NCBI View Article : Google Scholar
25	Du JL, Wang YL, Shi HY, Guo AT and Wei LX: Expression of glypican-3, hepatocyte antigen, alpha-fetoprotein, CD34 and CD10 in hepatocellular carcinoma: A clinicopathologic analysis of 375 cases. Zhonghua Bing Li Xue Za Zhi. 41:309–13. 2012.PubMed/NCBI View Article : Google Scholar : (In Chinese).
26	Cui DJ, Wu Y and Wen DH: CD34, PCNA and CK19 expressions in AFP-hepatocellular carcinoma. Eur Rev Med Pharmacol Sci. 22:5200–5205. 2018.PubMed/NCBI View Article : Google Scholar
27	Surcel M, Huică RI, Munteanu AN, Isvoranu G, Pîrvu IR, Ciotaru D, Constantin C, Bratu O, Căruntu C, Neagu M and Ursaciuc C: Phenotypic changes of lymphocyte populations in psoriasiform dermatitis animal model. Exp Ther Med. 17:1030–1038. 2019.PubMed/NCBI View Article : Google Scholar
28	Plotogea O, Ilie M, Sandru V, Chiotoroiu A, Bratu O and Diaconu C: Cardiovascular and metabolic consequences of liver transplantation: A review. Medicina (Kaunas). 55(E489)2019.PubMed/NCBI View Article : Google Scholar
29	Nasir A, Lehrke HD, Mounajjed T, Said S, Zhang L, Yasir S, Shah SS, Chandan VS, Smyrk TC, Moreira RK, et al: Albumin in situ hybridization can be positive in adenocarcinomas and other tumors from diverse sites. Am J Clin Pathol. 152:190–199. 2019.PubMed/NCBI View Article : Google Scholar
30	Kakar S, Muir T, Murphy LM, Lloyd RV and Burgart LJ: Immunoreactivity of Hep Par 1 in hepatic and extrahepatic tumours and its correlation with albumin in situ hybridization in hepatocellular carcinoma. Am J Clin Pathol. 119:361–366. 2003.PubMed/NCBI View Article : Google Scholar
31	Shahid M, Mubeen A, Tse J, Kakar S, Bateman AC, Borger D, Rivera MN, Ting DT and Deshpande V: Branched chain in situ hybridization for albumin as a marker of hepatocellular differentiation: Evaluation of manual and automated in situ hybridization platforms. Am J Surg Pathol. 39:25–34. 2015.PubMed/NCBI View Article : Google Scholar
32	Fang YW: Expression and significance of hTERT, c-myc and Ki-67 in hepatocellular carcinoma. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 25:338–340. 2009.PubMed/NCBI(In Chinese).
33	Zhou X, Zhu H and Lu J: PTEN and hTERT gene expression and the correlation with human hepatocellular carcinoma. Pathol Res Pract. 211:316–319. 2015.PubMed/NCBI View Article : Google Scholar