Wang Hanlin L, Anatelli Florencia, Zhai Qihui Jim, Adley Brian, Chuang Shang-Tian, Yang Ximing J
Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
Arch Pathol Lab Med. 2008 Nov;132(11):1723-8. doi: 10.5858/132.11.1723.
Histopathologic distinction between hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions, particularly hepatocellular adenoma, can sometimes be challenging. The currently available ancillary tools are suboptimal in terms of sensitivity and specificity.
To further characterize the diagnostic value of glypican-3 (GPC3), a cell surface proteoglycan that has recently been shown to be overexpressed in HCC, in the distinction between HCC and benign hepatocellular mass lesions.
A total of 221 surgically resected liver specimens were subjected to immunohistochemical staining using a monoclonal antibody specific for GPC3. These included 111 HCCs, 48 hepatocellular adenomas, 30 focal nodular hyperplasias, and 32 large regenerative nodules in the background of cirrhosis.
Cytoplasmic, membranous, and canalicular staining for GPC3 was detected in 84 (75.7%) of the 111 HCCs, among which, 61 (72.6%) of the 84 cases exhibited diffuse immunoreactivity. In contrast, none of the 110 cases of hepatocellular adenoma, focal nodular hyperplasia, and large regenerative nodule showed detectable GPC3 staining. Focal GPC3 immunoreactivity was detected in cirrhotic nodules in 11 (16.4%) of 67 HCC cases with a cirrhotic background, but no background staining was observed in the remaining 44 HCCs without cirrhosis. GPC3 expression in HCCs did not correlate with the size, differentiation, or stage of the tumors; the presence or absence of cirrhotic background; or the underlying etiologies.
GPC3 is a specific immunomarker for HCC that can be used to distinguish HCC from benign hepatocellular mass lesions, particularly hepatocellular adenoma. However, the diagnosis of HCC should not rely entirely on positive GPC3 immunostaining because focal immunoreactivity can be detected in a small subset of cirrhotic nodules. In addition, GPC3 expression in HCC can also be focal, and thus, the lack of GPC3 staining does not exclude the diagnosis of HCC.
肝细胞癌（HCC）与良性肝细胞肿块性病变，尤其是肝细胞腺瘤之间的组织病理学区分有时具有挑战性。目前可用的辅助工具在敏感性和特异性方面并不理想。
进一步明确磷脂酰肌醇蛋白聚糖-3（GPC3）在肝细胞癌与良性肝细胞肿块性病变鉴别诊断中的诊断价值，GPC3是一种细胞表面蛋白聚糖，最近研究表明其在HCC中过表达。
使用针对GPC3的单克隆抗体对221例手术切除的肝脏标本进行免疫组织化学染色。这些标本包括111例HCC、48例肝细胞腺瘤、30例局灶性结节性增生以及32例肝硬化背景下的大再生结节。
111例HCC中有84例（75.7%）检测到GPC3的细胞质、细胞膜及胆小管染色，其中84例中有61例（72.6%）表现为弥漫性免疫反应。相比之下，110例肝细胞腺瘤、局灶性结节性增生及大再生结节均未检测到GPC3染色。在67例有肝硬化背景的HCC病例中，11例（16.4%）的肝硬化结节中检测到局灶性GPC3免疫反应，但其余44例无肝硬化的HCC未观察到背景染色。HCC中GPC3的表达与肿瘤大小、分化程度、分期、有无肝硬化背景或潜在病因均无相关性。
GPC3是HCC的一种特异性免疫标志物，可用于将HCC与良性肝细胞肿块性病变，尤其是肝细胞腺瘤相鉴别。然而，HCC的诊断不应完全依赖GPC3免疫染色阳性，因为在一小部分肝硬化结节中可检测到局灶性免疫反应。此外，HCC中GPC3的表达也可能是局灶性的，因此，GPC3染色阴性并不能排除HCC的诊断。
