Squamous cell carcinoma antigen in human liver carcinogenesis.

Background: Squamous cell carcinoma antigen (SCCA) is a serine protease inhibitor that can be overexpressed in hepatocellular carcinoma (HCC) at both molecular and protein level, but no data are available on its expression in pre-malignant stages. Aim: To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers. Methods: 55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 lowgrade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semi-quantitatively scored on a four-tiered scale. Results: SCCA hepatocyte immunostaining was always restricted to the cytoplasm, mainly exhibiting a granular pattern. Stain intensity varied, ranging from weak to very strong. Within the nodules, positive cells were unevenly distributed, either scattered or in irregular clusters. The prevalence of SCCA expression was 29% in LRNs, 100% in DNs and 93% in HCC. A significant difference emerged in both prevalence and score for LRNs versus LG-DNs (p < 0.039), HG- DNs (p= 0.001), and HCC (p= 0.000). A barely significant difference (p= 0.49) was observed between LG-DNs and HG- DNs, while no difference in SCCA expression was detected between HG- DNs and HCC. Cirrhotic tissue adjacent to the nodules was positive in 96% of cases, with a significant difference in the score (p= 0.000) between hepatocytes adjacent to HCC and those surrounding LRNs. Discussion: This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.