H19 expression in hepatic metastases from a range of human carcinomas

Abstract

Aims: To investigate the expression of the imprinted oncofetal H19 gene in hepatic metastases derived from a range of human carcinomas and assess its prognostic value with the view of developing a DNA based treatment for such metastases. Methods: Non-radioactive in situ hybridisation for H19 RNA was performed on paraffin wax embedded sections of liver biopsies or partial hepatectomy specimens, taken from 80 patients with hepatic metastases derived from carcinomas from several medical centres in Israel. The degree of expression was graded qualitatively according to the number of cells expressing H19 and the intensity of staining. The medical files were searched for demographic data and survival times before and after diagnosis of hepatic metastases. Results: H19 expression was found in the hepatic metastases of 64 of 80 patients. High expression (higher staining grades) of H19 in the metastases was found in 43 of 80 patients. However, H19 expression status in the hepatic metastases did not correlate with either the length of time to development of metastasis or overall survival. Conclusions: H19 is highly expressed in more than half of hepatic metastases derived from a range of carcinomas. Thus, these metastases may be suitable candidates for H19 DNA based treatment. Further studies are needed to determine whether H19 expression has prognostic value in metastatic liver disease using larger numbers of specific subtypes of primary carcinomas.T he liver is one of the major sites of cancer metastasis. 1The most common primary malignancies producing hepatic metastases are carcinomas originating in the gastrointestinal tract, breast, and lung, in addition to melanoma, but cancer from any site may spread to the liver. 1 This is often an ominous sign, indicating poor prognosis. 1 However, it has been shown that in cases of colon and perhaps even breast carcinoma with a limited number of metastases, partial hepatectomy can provide hope for longterm survival. Other treatment methods for hepatic metastases include hepatic arterial chemotherapy, systemic chemotherapy, chemoembolisation, and several ablative techniques such as ethanol injection, cryoablation, radiofrequency ablation, microwave ablation, interstitial laser photocoagulation, and high intensity focused ultrasound. [3][4][5] All these methods have some, albeit limited, success in extending patient survival or in palliative treatment. [3][4][5][6][7] There are also some promising novel therapeutic modalities based on the molecular biology of metastasis in various phases of development.8 These include: antiangiogenesis agents, metalloprotease inhibitors, immunotherapy, and gene therapy based treatment strategies. ''The aim of our present study was to determine whether H19 is expressed in hepatic metastases from a range of human carcinomas, with a view to establishing the mechanistic basis for developing a DNA based treatment for such metastases'' H19 is an imprinted, maternally expressed oncofetal gene that functions as an RNA molecule. 9 H19 resides on chromosome ...

Long non-coding RNAs in cancer invasion and metastasis

“…50 Adriaenssens et al 51 have suggested that H19 has a role in epithelialmesenchymal interactions and thus in morphogenesis and/or migration of epithelial cells. A previous study has shown that H19 is highly expressed in hepatic metastases from a range of human carcinomas, 52 although the underlying mechanism has not been clearly shown. A recent study suggested that upregulated H19 enhances bladder cancer metastasis by associating with EZH2, resulting in Wnt/b-catenin activation and the subsequent downregulation of CDH1.…”

Regional therapy with DTA-H19 vector suppresses growth of colon adenocarcinoma metastases in the rat liver

“…H19 was found highly expressed and /or manifest aberrant allelic pattern of expression in over 30 types of cancer (14). Investigation of the expression of the H19 gene in hepatic metastases derived from a range of human carcinomas showed that H19 is highly expressed in the majority of hepatic metastases tested (18). Moreover, in the first report on the importance of the Twist gene product in tumor metastasis, the investigators showed that H19 is the highest differentially expressed gene in metastatic tumor cell lines investigated (19).…”

Aflatoxin B1 Promotes Cell Growth and Invasion in Hepatocellular Carcinoma HepG2 Cells through H19 and E2F1

“…H19 is an imprinted oncofetal gene, and loss of imprinting at the H19 locus resulted in over-expression of H19 in cancers of the esophagus, colon, liver, bladder and hepatic metastases (Hibi et al, 1996;Fellig et al, 2005;Matouk et al, 2007). H19 has been implicated as having both oncogenic and tumor suppression properties in cancer.…”