The incidence of hepatocellular carcinoma (HCC) is 750,000 new cases globally, it is the second leading cause of cancer-related death and represents a major health problem. When identified at early stages, curative treatments such as resection, transplantation and percutaneous ablation are feasible. Surveillance programs established in developed countries allow for early detection in 50% of cases. Candidates for entering surveillance are mostly cirrhotic patients that account for 1% of the human population. Around half of the nodules identified in the setting of these programs are ultimately malignant. In fact, small nodules of 1- 2 cm are difficult to characterize by radiologic or pathologic examination. Different signatures using immunohistochemistry (IHC) have been developed to accurately discriminate dysplastic nodules from early tumors. Among those, a panel of three IHC markers [glypican 3 (GPC3), glutamine synthase (GS), and heat shock protein 70 (HSP70)] has been recently proposed. Another approach uses CD34 and α-fetoprotein (AFP) immunostaining. Nevertheless, both panels have significant diagnostic limitations. Noninvasive radiologic techniques and serum biomarkers have also proved to be inaccurate
Dr. Josep Llovet, Director of the Liver Cancer Program and Professor of Medicine at Mount Sinai Health System, has developed a molecular diagnosis based on a 3-gene signature for the differential diagnosis of dysplastic nodules from early tumors in hepatitis C virus (HCV) patients. The combined mRNA analysis provides an accurate, simple and objective diagnosis of the nature of the lesion, applicable in routine clinical use. This model has a sensitivity and specificity of 95% and 94% respectively. It also carries a positive predictive value of 95%, a negative predictive value of 94% and a likelihood ratio for a positive result of 16.
Current Development Status
- The 3-gene panel is currently under investigation in a cohort of nodule-in-nodule samples which morphologically represents a carcinoma in situ HCC within a well-delimited high grade dysplastic nodules
Applications
- 3-gene panel diagnostic for early detection of hepatocellular carcinoma (HCC)
Advantages
- Ability to distinguish early HCC from other entities (mostly dysplastic nodules) with high sensitivity and specificity
- Earlier diagnosis of HCC will lead to an increase in applicability of curative procedures, and ultimately to decrease cancer-related death
- Technically simple, more accurate and cost effective diagnostic model compared to current methods
Publications
- Josep M. Llovet et al. “A molecular signature to discriminate dysplastic nodules from early hepatocellular carcinoma in HCV cirrhosis.” Gastroenterology 2006; 131:1758-1767
Patent Status
- US Application No. 11/735,402 filed April 13, 2007
- Status: Issued. US Patent No. 8,030,013
Contact
Idoia Gamez, PhD, MBA
Business Development Director
Mount Sinai Innovation Partners | Icahn School of Medicine at Mount Sinai
Phone: 646.605.7317