Chromosomal Abnormalities Determined by Comparative Genomic Hybridization Are Helpful in the Diagnosis of Atypical Hepatocellular Neoplasms

Overview

Journal Histopathology

Specialties Anatomy & Histology
Pathology

Date 2009 Aug 22

PMID 19694827

Citations 12

Authors

Sanjay Kakar

Xin Chen

Coral Ho

Lawrence J Burgart

Oyedele Adeyi

Dhanpat Jain

Viabhav Sahai

Linda D Ferrell

Affiliations

Soon will be listed here.

Abstract

Aims: To explore the utility of cytogenetic abnormalities in the distinction of hepatic adenoma (HA) and well-differentiated hepatocellular carcinoma (HCC).

Methods And Results: Array-based comparative genomic hybridization (CGH) was used to determine chromosomal abnormalities in 39 hepatocellular neoplasms: 12 HA, 15 atypical hepatocellular neoplasms (AHN) and 12 well-differentiated HCC. The designation of AHN was used in two situations: (i) adenoma-like neoplasms (n = 8) in male patients (any age) and women >50 years and <15 years old; (ii) adenoma-like neoplasms with focal atypical features (n = 7). CGH abnormalities were seen in none of the HAs (0/12), eight (53%) AHNs and 11 (92%) HCCs. The number and nature of abnormalities in AHN was similar to HCC with gains in 1q, 8q and 7q being the most common. Although follow-up information was limited, recurrence and/or metastasis were observed in three AHNs (two with abnormal, one with normal CGH).

Conclusions: Adenoma-like neoplasms with focal atypical morphological features or unusual clinical settings such as male gender or women outside the 15-50 year age group can show chromosomal abnormalities similar to well-differentiated HCC. Even though these tumours morphologically mimic adenoma, they can recur and metastasize. Determination of chromosomal abnormalities can be useful in the diagnosis of AHN.

Citing Articles

Hepatocellular adenoma in the paediatric population: Molecular classification and clinical associations.

Hahn E, Putra J World J Gastroenterol. 2020; 26(19):2294-2304.

PMID: 32476794 PMC: 7243640. DOI: 10.3748/wjg.v26.i19.2294.

gene function during hepatoma cells proliferation.

Vega-Benedetti A, Saucedo C, Zavattari P, Vanni R, Royo F, Llavero F Oncotarget. 2018; 9(67):32775-32794.

PMID: 30214684 PMC: 6132347. DOI: 10.18632/oncotarget.25996.

Malignant transformation of hepatocellular adenoma.

Sempoux C, Balabaud C, Bioulac-Sage P Hepat Oncol. 2018; 1(4):421-431.

PMID: 30190977 PMC: 6095435. DOI: 10.2217/hep.14.14.

Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma.

Hale G, Liu X, Hu J, Xu Z, Che L, Solomon D Mod Pathol. 2016; 29(11):1370-1380.

PMID: 27469330 PMC: 5149418. DOI: 10.1038/modpathol.2016.122.

Molecular alterations in hepatocellular carcinoma associated with hepatitis B and hepatitis C infections.

Tornesello M, Buonaguro L, Izzo F, Buonaguro F Oncotarget. 2016; 7(18):25087-102.

PMID: 26943571 PMC: 5041890. DOI: 10.18632/oncotarget.7837.

References

Reddy K, Kligerman S, Levi J, Livingstone A, Molina E, Franceschi D . Benign and solid tumors of the liver: relationship to sex, age, size of tumors, and outcome. Am Surg. 2001; 67(2):173-8. View

Balsara B, Pei J, De Rienzo A, Simon D, Tosolini A, Lu Y . Human hepatocellular carcinoma is characterized by a highly consistent pattern of genomic imbalances, including frequent loss of 16q23.1-24.1. Genes Chromosomes Cancer. 2001; 30(3):245-53. DOI: 10.1002/1098-2264(2000)9999:9999<::aid-gcc1083>3.0.co;2-m. View

Coston W, Loera S, Lau S, Ishizawa S, Jiang Z, Wu C . Distinction of hepatocellular carcinoma from benign hepatic mimickers using Glypican-3 and CD34 immunohistochemistry. Am J Surg Pathol. 2008; 32(3):433-44. DOI: 10.1097/PAS.0b013e318158142f. View

Ferrell L, Crawford J, Dhillon A, Scheuer P, Nakanuma Y . Proposal for standardized criteria for the diagnosis of benign, borderline, and malignant hepatocellular lesions arising in chronic advanced liver disease. Am J Surg Pathol. 1993; 17(11):1113-23. DOI: 10.1097/00000478-199311000-00004. View

Wilkens L, Bredt M, Flemming P, Schwarze Y, Becker T, Mengel M . Diagnostic impact of fluorescence in situ hybridization in the differentiation of hepatocellular adenoma and well-differentiated hepatocellular carcinoma. J Mol Diagn. 2001; 3(2):68-73. PMC: 1907351. DOI: 10.1016/S1525-1578(10)60654-X. View

Wang X, Degos F, Dubois S, Tessiore S, Allegretta M, Guttmann R . Glypican-3 expression in hepatocellular tumors: diagnostic value for preneoplastic lesions and hepatocellular carcinomas. Hum Pathol. 2006; 37(11):1435-41. DOI: 10.1016/j.humpath.2006.05.016. View

Nasarek A, Werner M, Nolte M, Klempnauer J, Georgii A . Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver cell adenoma and focal nodular hyperplasia. A fluorescence in situ hybridization study. Virchows Arch. 1995; 427(4):373-8. DOI: 10.1007/BF00199385. View

Wilkens L, Bredt M, Flemming P, Becker T, Klempnauer J, Kreipe H . Differentiation of liver cell adenomas from well-differentiated hepatocellular carcinomas by comparative genomic hybridization. J Pathol. 2001; 193(4):476-82. DOI: 10.1002/path.825. View

Jain A, Tokuyasu T, Snijders A, Segraves R, Albertson D, Pinkel D . Fully automatic quantification of microarray image data. Genome Res. 2002; 12(2):325-32. PMC: 155276. DOI: 10.1101/gr.210902. View

10.

Poon T, Wong N, Lai P, Rattray M, Johnson P, Sung J . A tumor progression model for hepatocellular carcinoma: bioinformatic analysis of genomic data. Gastroenterology. 2006; 131(4):1262-70. DOI: 10.1053/j.gastro.2006.08.014. View

11.

Shafizadeh N, Ferrell L, Kakar S . Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum. Mod Pathol. 2008; 21(8):1011-8. DOI: 10.1038/modpathol.2008.85. View

12.

Patil M, Gutgemann I, Zhang J, Ho C, Cheung S, Ginzinger D . Array-based comparative genomic hybridization reveals recurrent chromosomal aberrations and Jab1 as a potential target for 8q gain in hepatocellular carcinoma. Carcinogenesis. 2005; 26(12):2050-7. DOI: 10.1093/carcin/bgi178. View

13.

Laurent-Puig P, Legoix P, Bluteau O, Belghiti J, Franco D, Binot F . Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis. Gastroenterology. 2001; 120(7):1763-73. DOI: 10.1053/gast.2001.24798. View

14.

Wong N, Lai P, Lee S, Fan S, Pang E, Liew C . Assessment of genetic changes in hepatocellular carcinoma by comparative genomic hybridization analysis: relationship to disease stage, tumor size, and cirrhosis. Am J Pathol. 1999; 154(1):37-43. PMC: 1853447. DOI: 10.1016/S0002-9440(10)65248-0. View

15.

Chuang W, Chen T, Hsu H, Lee W, Jeng L, Huang S . Liver cell adenoma with concomitant hepatocellular carcinoma: report of two cases. J Formos Med Assoc. 2003; 101(11):798-802. View

16.

Tesluk H, Lawrie J . Hepatocellular adenoma. Its transformation to carcinoma in a user of oral contraceptives. Arch Pathol Lab Med. 1981; 105(6):296-9. View

17.

Burri E, Steuerwald M, Cathomas G, Mentha G, Majno P, Rubbia-Brandt L . Hepatocellular carcinoma in a liver-cell adenoma within a non-cirrhotic liver. Eur J Gastroenterol Hepatol. 2006; 18(4):437-41. DOI: 10.1097/00042737-200604000-00020. View

18.

Terkivatan T, de Wilt J, de Man R, van Rijn R, Zondervan P, Tilanus H . Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal. Arch Surg. 2001; 136(9):1033-8. DOI: 10.1001/archsurg.136.9.1033. View

19.

Moinzadeh P, Breuhahn K, Stutzer H, Schirmacher P . Chromosome alterations in human hepatocellular carcinomas correlate with aetiology and histological grade--results of an explorative CGH meta-analysis. Br J Cancer. 2005; 92(5):935-41. PMC: 2361895. DOI: 10.1038/sj.bjc.6602448. View

20.

Bioulac-Sage P, Rebouissou S, Thomas C, Blanc J, Saric J, Sa Cunha A . Hepatocellular adenoma subtype classification using molecular markers and immunohistochemistry. Hepatology. 2007; 46(3):740-8. DOI: 10.1002/hep.21743. View