Guido M, Roskams T, Pontisso P, Fassan M, Thung S N, Giacomelli L, Sergio A, Farinati F, Cillo U, Rugge M
Department of Diagnostic Medical Sciences & Special Therapies, Universitè degli Studi di Padova, Italy.
J Clin Pathol. 2008 Apr;61(4):445-7. doi: 10.1136/jcp.2007.051383. Epub 2007 Sep 24.
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.
To assess SCCA expression by immunohistochemistry in HCC and its nodular precursors in cirrhotic livers.
55 nodules from 42 explanted livers were evaluated: 7 large regenerative nodules (LRNs), 7 low-grade dysplastic nodules (LG-DNs), 10 high-grade DNs (HG-DNs), and 31 HCC. SCCA expression was semiquantitatively scored on a four-tiered scale.
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.
This study provides the first evidence that aberrant SCCA expression is an early event in liver cell carcinomatous transformation.
鳞状细胞癌抗原（SCCA）是一种丝氨酸蛋白酶抑制剂，在肝细胞癌（HCC）中可在分子和蛋白质水平上过度表达，但关于其在癌前阶段的表达尚无数据。
通过免疫组织化学评估SCCA在HCC及其肝硬化肝脏中的结节前体中的表达。
对42例移植肝脏中的55个结节进行评估：7个大再生结节（LRN）、7个低级别发育异常结节（LG-DN）、10个高级别发育异常结节（HG-DN）和31个HCC。SCCA表达采用四级量表进行半定量评分。
SCCA在肝细胞中的免疫染色始终局限于细胞质，主要呈颗粒状。染色强度各不相同，从弱到非常强。在结节内，阳性细胞分布不均，呈散在或不规则簇状。SCCA表达的发生率在LRN中为29%，在DN中为100%，在HCC中为93%。LRN与LG-DN（p<0.039）、HG-DN（p = 0.001）和HCC（p = 0.000）在发生率和评分上均出现显著差异。LG-DN和HG-DN之间观察到的差异几乎无统计学意义（p = 0.49），而HG-DN和HCC之间未检测到SCCA表达的差异。结节周围的肝硬化组织在96%的病例中呈阳性，HCC周围的肝细胞与LRN周围的肝细胞在评分上存在显著差异（p = 0.000）。
本研究首次提供证据表明SCCA异常表达是肝细胞癌变转化的早期事件。
