Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Mod Pathol. 2010 Sep;23(9):1180-90. doi: 10.1038/modpathol.2010.105. Epub 2010 May 21.
Fibrolamellar carcinoma is a rare malignant primary liver neoplasm with characteristic histological features that typically arises in young patients without viral hepatitis or cirrhosis. Previous studies on this entity have been limited by small numbers of patients. In contrast to classical hepatocellular carcinoma, individual cases of fibrolamellar carcinoma have been reported to express cytokeratin 7. In addition, ultrastructural and serological studies have suggested that fibrolamellar carcinoma may show neuroendocrine differentiation. The cellular differentiation of fibrolamellar carcinoma has not been studied and little is reported about its immunohistochemical profile. We studied 26 cases of fibrolamellar carcinoma and 62 cases of classical hepatocellular carcinoma by immunohistochemistry for HepPar1, glypican-3, pCEA, CD10, alpha-fetoprotein, cytokeratin 20, neuroendocrine markers, and surrogate markers for biliary differentiation (cytokeratin 7, cytokeratin 19, epithelial membrane antigen, EpCAM, mCEA, B72.3, and CA19.9). In situ hybridization for albumin mRNA was also performed. Tumor cells of fibrolamellar carcinoma and hepatocellular carcinoma showed positive signals for albumin mRNA by in situ hybridization in all cases. Both tumor types stained uniformly positively with HepPar1 and most showed a canalicular staining pattern for pCEA, confirming their hepatocellular differentiation. In addition, 39% of hepatocellular carcinoma cases and 59% of fibrolamellar carcinoma cases were positive for glypican-3. All 22 fibrolamellar carcinoma cases tested showed positive staining for cytokeratin 7 and epithelial membrane antigen, whereas less than one-third of hepatocellular carcinoma cases were positive for these markers (P<0.0001). Further, 36% of fibrolamellar carcinoma cases showed staining for B72.3, cytokeratin 19, EpCAM, or mCEA. Minimal evidence of neuroendocrine differentiation in either tumor was found with any of the usual immunohistochemical markers used for this purpose. Therefore, cytokeratin 7 and epithelial membrane antigen may be useful to differentiate between fibrolamellar carcinoma and hepatocellular carcinoma. On the basis of immunohistochemistry, fibrolamellar carcinoma seems to show both hepatocellular and bile duct differentiation.
纤维板层样肝细胞癌是一种罕见的恶性原发性肝肿瘤，具有特征性的组织学特征，通常发生在无病毒性肝炎或肝硬化的年轻患者中。以前对该实体的研究受到患者数量少的限制。与经典的肝细胞癌不同，个别纤维板层样肝细胞癌已被报道表达细胞角蛋白 7。此外，超微结构和血清学研究表明，纤维板层样肝细胞癌可能表现出神经内分泌分化。纤维板层样肝细胞癌的细胞分化尚未得到研究，其免疫组织化学特征也鲜有报道。我们通过免疫组织化学法对 26 例纤维板层样肝细胞癌和 62 例经典肝细胞癌进行了 HepPar1、glypican-3、pCEA、CD10、甲胎蛋白、细胞角蛋白 20、神经内分泌标志物以及胆管分化的替代标志物（细胞角蛋白 7、细胞角蛋白 19、上皮膜抗原、EpCAM、mCEA、B72.3 和 CA19.9）的检测。还进行了白蛋白 mRNA 的原位杂交。所有病例的纤维板层样肝细胞癌和肝细胞癌的肿瘤细胞均通过原位杂交显示出白蛋白 mRNA 的阳性信号。两种肿瘤类型均均匀地对 HepPar1 呈阳性染色，大多数对 pCEA 呈管腔染色模式，证实了它们的肝细胞分化。此外，39%的肝细胞癌病例和 59%的纤维板层样肝细胞癌病例对 glypican-3 呈阳性。我们检测的所有 22 例纤维板层样肝细胞癌均对细胞角蛋白 7 和上皮膜抗原呈阳性染色，而不到三分之一的肝细胞癌病例对这些标志物呈阳性（P<0.0001）。此外，36%的纤维板层样肝细胞癌病例对 B72.3、细胞角蛋白 19、EpCAM 或 mCEA 呈阳性染色。用通常用于此目的的任何免疫组织化学标志物都很少发现两种肿瘤中存在神经内分泌分化的证据。因此，细胞角蛋白 7 和上皮膜抗原可能有助于区分纤维板层样肝细胞癌和肝细胞癌。根据免疫组织化学，纤维板层样肝细胞癌似乎表现出肝细胞和胆管分化。
