Abstract：
The methylated SEPT9 DNA ( mSEPT9 ) in plasma is a US Food and Drug Administration (FDA)-approved screening biomarker in colorectal cancer and is emerging as a promising diagnostic and prognostic biomarker in hepatocellular carcinoma (HCC). We evaluated the SEPT9 protein expression by immunohistochemistry (IHC) in various hepatic tumors from 164 hepatectomies and explants. Cases diagnosed as HCC (n=68), hepatocellular adenoma (n=31), dysplastic nodule (n=24), and metastasis (n=41) were retrieved. SEPT9 stain was performed on representative tissue blocks showing tumor/liver interface. For HCC, archived IHC (SATB2, CK19, CDX2, CK20, and CDH17) slides were also reviewed. The findings were correlated with demographics, risk factors, tumor size, alpha fetoprotein levels at diagnosis, T stage and oncologic outcomes, with significance defined as P <0.05. Percentage of SEPT9 positivity differed significantly among hepatocellular adenoma (3%), dysplastic nodule (0%), HCC (32%), and metastasis (83%, P <0.001). Compared with patients with SEPT9- HCC, those with SEPT9+ HCC were older (70 vs. 63 y, P =0.01). The extent of SEPT9 staining correlated with age ( rs =0.31, P =0.01), tumor grade ( rs =0.30, P =0.01), and extent of SATB2 staining ( rs =0.28, P =0.02). No associations were found between SEPT9 staining and tumor size, T stage, risk factors, CK19, CDX2, CK20, or CDH17 expression, alpha fetoprotein levels at diagnosis, METAVIR fibrosis stage, and oncologic outcome in the HCC cohort. SEPT9 is likely implicated in liver carcinogenesis in a HCC subset. Similar to mSEPT9 DNA measurement in liquid biopsies, SEPT9 staining by IHC may prove helpful as an adjunct diagnostic biomarker with potential prognostic ramifications.
摘要：
血浆中的甲基化SEPT9DNA（mSEPT9）是美国食品药品监督管理局（FDA）批准的结直肠癌筛查生物标志物，并且正在成为肝细胞癌（HCC）中有前途的诊断和预后生物标志物。我们通过免疫组织化学（IHC）评估了来自164个肝切除术和外植体的各种肝肿瘤中SEPT9蛋白的表达。诊断为HCC的病例（n=68），肝细胞腺瘤（n=31），发育不良结节（n=24），和转移（n=41）。在显示肿瘤/肝界面的代表性组织块上进行SEPT9染色。对于HCC，同时回顾了存档的IHC(SATB2,CK19,CDX2,CK20和CDH17)载玻片.这些发现与人口统计学相关，危险因素，肿瘤大小,诊断时甲胎蛋白水平，T期和肿瘤学结果，显著性定义为P<0.05。SEPT9阳性的百分比在肝细胞腺瘤中存在显着差异（3％），发育不良结节（0%），肝癌（32%），和转移(83%，P<0.001)。与SEPT9-HCC患者相比，SEPT9+HCC患者年龄较大（70vs.63y,P=0.01）。SEPT9染色程度与年龄相关(rs=0.31,P=0.01),肿瘤分级(rs=0.30,P=0.01),和SATB2染色的程度（rs=0.28，P=0.02）。没有发现SEPT9染色和肿瘤大小之间的关联，T级,危险因素，CK19、CDX2、CK20或CDH17表达，诊断时甲胎蛋白水平，METAVIR纤维化分期，和HCC队列中的肿瘤学结果。SEPT9可能与HCC亚组的肝癌发生有关。类似于液体活检中的mSEPT9DNA测量，通过IHC的SEPT9染色可能被证明作为具有潜在预后后果的辅助诊断生物标志物。
