Abstract
AIMS/BACKGROUND: To study the expression of the H19 gene in hepatocellular carcinoma. H19 is an imprinted, maternally expressed gene, which is tightly linked, both physically and functionally, to the paternally expressed insulin-like growth factor 2 (IGF II). IGF II is known to be involved in liver carcinogenesis. H19 was first discovered in the fetal mouse liver to be under the same regulatory genes as alpha fetoprotein (alpha FP), a widely used tumour marker for hepatocellular carcinoma. METHODS: Using both radioactive and non-radioactive in situ hybridisation, the expression of the H19 gene was compared with the presence of alpha FP, as demonstrated by immunohistochemistry, in 18 cases of hepatocellular carcinoma. RESULTS: H19 expression was present in 13 of 18 cases, whereas staining for alpha FP was positive in only nine of 18 cases. Concordance was found in 12 of 18 tumours (66.7%). In general, the staining pattern for H19 was more diffuse than the immunohistochemical staining for alpha FP. CONCLUSIONS: The addition of a non-radioactive in situ hybridisation assay for H19 RNA to the panel of tumour markers used for the histopathological and cytological diagnosis of hepatocellular carcinoma might be useful.
Full Text
The Full Text of this article is available as a PDF (247.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abelev G. I. Alpha-fetoprotein: 25 years of study. Tumour Biol. 1989;10(2):63–74. doi: 10.1159/000217596. [DOI] [PubMed] [Google Scholar]
- Ariel I., Ayesh S., Perlman E. J., Pizov G., Tanos V., Schneider T., Erdmann V. A., Podeh D., Komitowski D., Quasem A. S. The product of the imprinted H19 gene is an oncofetal RNA. Mol Pathol. 1997 Feb;50(1):34–44. doi: 10.1136/mp.50.1.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ariel I., Lustig O., Oyer C. E., Elkin M., Gonik B., Rachmilewitz J., Biran H., Goshen R., de Groot N., Hochberg A. Relaxation of imprinting in trophoblastic disease. Gynecol Oncol. 1994 May;53(2):212–219. doi: 10.1006/gyno.1994.1118. [DOI] [PubMed] [Google Scholar]
- Ariel I., Lustig O., Schneider T., Pizov G., Sappir M., De-Groot N., Hochberg A. The imprinted H19 gene as a tumor marker in bladder carcinoma. Urology. 1995 Feb;45(2):335–338. doi: 10.1016/0090-4295(95)80030-1. [DOI] [PubMed] [Google Scholar]
- Ariel I., Weinstein D., Voutilainen R., Schneider T., Lustig-Yariv O., de Groot N., Hochberg A. Genomic imprinting and the endometrial cycle. The expression of the imprinted gene H19 in the human female reproductive organs. Diagn Mol Pathol. 1997 Feb;6(1):17–25. doi: 10.1097/00019606-199702000-00004. [DOI] [PubMed] [Google Scholar]
- Biran H., Ariel I., de Groot N., Shani A., Hochberg A. Human imprinted genes as oncodevelopmental markers. Tumour Biol. 1994;15(3):123–134. doi: 10.1159/000217882. [DOI] [PubMed] [Google Scholar]
- Brannan C. I., Dees E. C., Ingram R. S., Tilghman S. M. The product of the H19 gene may function as an RNA. Mol Cell Biol. 1990 Jan;10(1):28–36. doi: 10.1128/mcb.10.1.28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brockdorff N., Ashworth A., Kay G. F., McCabe V. M., Norris D. P., Cooper P. J., Swift S., Rastan S. The product of the mouse Xist gene is a 15 kb inactive X-specific transcript containing no conserved ORF and located in the nucleus. Cell. 1992 Oct 30;71(3):515–526. doi: 10.1016/0092-8674(92)90519-i. [DOI] [PubMed] [Google Scholar]
- Cariani E., Lasserre C., Seurin D., Hamelin B., Kemeny F., Franco D., Czech M. P., Ullrich A., Brechot C. Differential expression of insulin-like growth factor II mRNA in human primary liver cancers, benign liver tumors, and liver cirrhosis. Cancer Res. 1988 Dec 1;48(23):6844–6849. [PubMed] [Google Scholar]
- Casola S., Ungaro P., Pedone P. V., Lazzaro D., Fattori E., Ciliberto G., Zarrilli R., Bruni C. B., Riccio A. Loss of heterozygosity of imprinted genes in SV40 t/T antigen-induced hepatocellular carcinomas. Oncogene. 1995 Aug 17;11(4):711–721. [PubMed] [Google Scholar]
- De Souza A. T., Yamada T., Mills J. J., Jirtle R. L. Imprinted genes in liver carcinogenesis. FASEB J. 1997 Jan;11(1):60–67. doi: 10.1096/fasebj.11.1.9034167. [DOI] [PubMed] [Google Scholar]
- Elkin M., Shevelev A., Schulze E., Tykocinsky M., Cooper M., Ariel I., Pode D., Kopf E., de Groot N., Hochberg A. The expression of the imprinted H19 and IGF-2 genes in human bladder carcinoma. FEBS Lett. 1995 Oct 23;374(1):57–61. doi: 10.1016/0014-5793(95)01074-o. [DOI] [PubMed] [Google Scholar]
- Eversole-Cire P., Ferguson-Smith A. C., Surani M. A., Jones P. A. Coordinate regulation of Igf-2 and H19 in cultured cells. Cell Growth Differ. 1995 Mar;6(3):337–345. [PubMed] [Google Scholar]
- Feinberg A. P. Genomic imprinting and gene activation in cancer. Nat Genet. 1993 Jun;4(2):110–113. doi: 10.1038/ng0693-110. [DOI] [PubMed] [Google Scholar]
- Fiorentino M., Grigioni W. F., Baccarini P., D'Errico A., De Mitri M. S., Pisi E., Mancini A. M. Different in situ expression of insulin-like growth factor type II in hepatocellular carcinoma. An in situ hybridization and immunohistochemical study. Diagn Mol Pathol. 1994 Mar;3(1):59–65. doi: 10.1097/00019606-199403010-00010. [DOI] [PubMed] [Google Scholar]
- Goshen R., Rachmilewitz J., Schneider T., de-Groot N., Ariel I., Palti Z., Hochberg A. A. The expression of the H-19 and IGF-2 genes during human embryogenesis and placental development. Mol Reprod Dev. 1993 Apr;34(4):374–379. doi: 10.1002/mrd.1080340405. [DOI] [PubMed] [Google Scholar]
- Guindi M., Yazdi H. M., Gilliatt M. A. Fine needle aspiration biopsy of hepatocellular carcinoma. Value of immunocytochemical and ultrastructural studies. Acta Cytol. 1994 May-Jun;38(3):385–391. [PubMed] [Google Scholar]
- Hao Y., Crenshaw T., Moulton T., Newcomb E., Tycko B. Tumour-suppressor activity of H19 RNA. Nature. 1993 Oct 21;365(6448):764–767. doi: 10.1038/365764a0. [DOI] [PubMed] [Google Scholar]
- Hochberg A., Gonik B., Goshen R., de Groot N. A growing relationship between genomic imprinting and tumorigenesis. Cancer Genet Cytogenet. 1994 Mar;73(1):82–83. doi: 10.1016/0165-4608(94)90188-0. [DOI] [PubMed] [Google Scholar]
- Hurlimann J., Gardiol D. Immunohistochemistry in the differential diagnosis of liver carcinomas. Am J Surg Pathol. 1991 Mar;15(3):280–288. doi: 10.1097/00000478-199103000-00008. [DOI] [PubMed] [Google Scholar]
- Kondo M., Suzuki H., Ueda R., Osada H., Takagi K., Takahashi T., Takahashi T. Frequent loss of imprinting of the H19 gene is often associated with its overexpression in human lung cancers. Oncogene. 1995 Mar 16;10(6):1193–1198. [PubMed] [Google Scholar]
- Leighton P. A., Ingram R. S., Eggenschwiler J., Efstratiadis A., Tilghman S. M. Disruption of imprinting caused by deletion of the H19 gene region in mice. Nature. 1995 May 4;375(6526):34–39. doi: 10.1038/375034a0. [DOI] [PubMed] [Google Scholar]
- Li X., Nong Z., Ekström C., Larsson E., Nordlinder H., Hofmann W. J., Trautwein C., Odenthal M., Dienes H. P., Ekström T. J. Disrupted IGF2 promoter control by silencing of promoter P1 in human hepatocellular carcinoma. Cancer Res. 1997 May 15;57(10):2048–2054. [PubMed] [Google Scholar]
- Lustig O., Ariel I., Ilan J., Lev-Lehman E., De-Groot N., Hochberg A. Expression of the imprinted gene H19 in the human fetus. Mol Reprod Dev. 1994 Jul;38(3):239–246. doi: 10.1002/mrd.1080380302. [DOI] [PubMed] [Google Scholar]
- Pachnis V., Belayew A., Tilghman S. M. Locus unlinked to alpha-fetoprotein under the control of the murine raf and Rif genes. Proc Natl Acad Sci U S A. 1984 Sep;81(17):5523–5527. doi: 10.1073/pnas.81.17.5523. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rachmilewitz J., Goshen R., Ariel I., Schneider T., de Groot N., Hochberg A. Parental imprinting of the human H19 gene. FEBS Lett. 1992 Aug 31;309(1):25–28. doi: 10.1016/0014-5793(92)80731-u. [DOI] [PubMed] [Google Scholar]
- Rastinejad F., Conboy M. J., Rando T. A., Blau H. M. Tumor suppression by RNA from the 3' untranslated region of alpha-tropomyosin. Cell. 1993 Dec 17;75(6):1107–1117. doi: 10.1016/0092-8674(93)90320-p. [DOI] [PubMed] [Google Scholar]
- Rogler C. E., Sherman M., Su C. Y., Shafritz D. A., Summers J., Shows T. B., Henderson A., Kew M. Deletion in chromosome 11p associated with a hepatitis B integration site in hepatocellular carcinoma. Science. 1985 Oct 18;230(4723):319–322. doi: 10.1126/science.2996131. [DOI] [PubMed] [Google Scholar]
- Su Q., Liu Y. F., Zhang J. F., Zhang S. X., Li D. F., Yang J. J. Expression of insulin-like growth factor II in hepatitis B, cirrhosis and hepatocellular carcinoma: its relationship with hepatitis B virus antigen expression. Hepatology. 1994 Oct;20(4 Pt 1):788–799. doi: 10.1002/hep.1840200404. [DOI] [PubMed] [Google Scholar]
- Tabor E. Tumor suppressor genes, growth factor genes, and oncogenes in hepatitis B virus-associated hepatocellular carcinoma. J Med Virol. 1994 Apr;42(4):357–365. doi: 10.1002/jmv.1890420406. [DOI] [PubMed] [Google Scholar]
- Taniguchi T., Sullivan M. J., Ogawa O., Reeve A. E. Epigenetic changes encompassing the IGF2/H19 locus associated with relaxation of IGF2 imprinting and silencing of H19 in Wilms tumor. Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2159–2163. doi: 10.1073/pnas.92.6.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tatarinov Y. S. The past and the future for cancer testing by alpha-fetoprotein. A review. J Nucl Med Allied Sci. 1989 Jul-Sep;33(3 Suppl):5–11. [PubMed] [Google Scholar]
- Tycko B. Genomic imprinting: mechanism and role in human pathology. Am J Pathol. 1994 Mar;144(3):431–443. [PMC free article] [PubMed] [Google Scholar]
- Ueda K., Ganem D. Apoptosis is induced by N-myc expression in hepatocytes, a frequent event in hepadnavirus oncogenesis, and is blocked by insulin-like growth factor II. J Virol. 1996 Mar;70(3):1375–1383. doi: 10.1128/jvi.70.3.1375-1383.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Voutilainen R., Ilvesmäki V., Ariel I., Rachmilewitz J., de Groot N., Hochberg A. Parallel regulation of parentally imprinted H19 and insulin-like growth factor-II genes in cultured human fetal adrenal cells. Endocrinology. 1994 May;134(5):2051–2056. doi: 10.1210/endo.134.5.7512497. [DOI] [PubMed] [Google Scholar]
- Wee A., Nilsson B., Tan L. K., Yap I. Fine needle aspiration biopsy of hepatocellular carcinoma. Diagnostic dilemma at the ends of the spectrum. Acta Cytol. 1994 May-Jun;38(3):347–354. [PubMed] [Google Scholar]
- Wevrick R., Kerns J. A., Francke U. Identification of a novel paternally expressed gene in the Prader-Willi syndrome region. Hum Mol Genet. 1994 Oct;3(10):1877–1882. doi: 10.1093/hmg/3.10.1877. [DOI] [PubMed] [Google Scholar]
- Yang D., Faris R., Hixson D., Affigne S., Rogler C. E. Insulin-like growth factor II blocks apoptosis of N-myc2-expressing woodchuck liver epithelial cells. J Virol. 1996 Sep;70(9):6260–6268. doi: 10.1128/jvi.70.9.6260-6268.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yballe C. M., Vu T. H., Hoffman A. R. Imprinting and expression of insulin-like growth factor-II and H19 in normal breast tissue and breast tumor. J Clin Endocrinol Metab. 1996 Apr;81(4):1607–1612. doi: 10.1210/jcem.81.4.8636375. [DOI] [PubMed] [Google Scholar]
- Zhang Y., Tycko B. Monoallelic expression of the human H19 gene. Nat Genet. 1992 Apr;1(1):40–44. doi: 10.1038/ng0492-40. [DOI] [PubMed] [Google Scholar]
- Zvibel I., Brill S., Reid L. M. Insulin-like growth factor II regulation of gene expression in rat and human hepatomas. J Cell Physiol. 1995 Jan;162(1):36–43. doi: 10.1002/jcp.1041620106. [DOI] [PubMed] [Google Scholar]
- d'Arville C. N., Nouri-Aria K. T., Johnson P., Williams R. Regulation of insulin-like growth factor II gene expression by hepatitis B virus in hepatocellular carcinoma. Hepatology. 1991 Feb;13(2):310–315. [PubMed] [Google Scholar]
- van Gurp R. J., Oosterhuis J. W., Kalscheuer V., Mariman E. C., Looijenga L. H. Biallelic expression of the H19 and IGF2 genes in human testicular germ cell tumors. J Natl Cancer Inst. 1994 Jul 20;86(14):1070–1075. doi: 10.1093/jnci/86.14.1070. [DOI] [PubMed] [Google Scholar]