A morpho-molecular prognostic model for hepatocellular carcinoma
British Journal of Cancer, 06/21/2012
Srivastava S et al. – The morpho–molecular prognostic model (MMPM), based on the expression of selected proteins and clinicopathological parameters, can be used to classify Hepatocellular carcinoma (HCC) patients between good vs poor prognosis and high vs low risk of recurrence following hepatic resection.Methods
- In all, 13 biomarkers related to the etiopathogenesis of HCC were evaluated by immunohistochemistry using tissue microarrays containing 121 primary HCC resection cases, and validated in subsequent cohort of 85 HCC cases.
- The results were compared with Affymetrix Gene Chip Human Genome U133Plus microarray data in a separate cohort of 228 HCC patients.
- On immunohistochemical evaluation and multivariate Cox regression analysis p53, alpha fetaprotein (AFP), CD44 and CD31, tumour size and vascular invasion, were significant predictors for worse survival in HCC patients.
- A morpho-molecular prognostic model (MMPM) was constructed and it was a significant independent predictor for overall survival (OS) and relapse-free survival (RFS) (P<0.000).
- The OS and RFS of HCClow was higher (104 and 78months) as compared with HCChigh (73 and 43months) (P<0.0001for OS and RFS).
- Hepatocellular carcinoma patients with higher stage (III+IV), >5cm tumour size, positive vascular invasion and satellitosis belonged to HCChigh group.
- The validation group reproduced the same findings.
- Gene expression analysis confirmed that 7 of the 12 biomarkers were overexpressed in >50% of tumour samples and significant overexpression in tumour samples was observed in AFP, CD31, CD117 and Ki-67 genes.