Fibrolamellár hepatocellular carcinoma. An immunohistochemical and ultrastructural study

Caballero, T.; Aneiros, José Antonio Ocampo; López-Caballero, José J; Gómez‐Morales, Mercedes; Nogales, F.

doi:10.1111/j.1365-2559.1985.tb02827.x

Cited by 37 publications

(13 citation statements)

References 19 publications

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“…Further studies in a larger number of fibrolamellar carcinomas will have to clarify whether a-HCG may have a marker function for this tumour. If this proves correct, it may be additional evidence that these tumours are biologically different from other types of hepatocellular carcinoma (Craig et al 1980, Caballero et al 1985, possibly being of neuroendocrine nature as has recently been suggested (Payne e f al, 1986).…”

Section: Discussionmentioning

confidence: 82%

The significance of alpha‐fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours

Brumm

Schulze

Karina³

et al. 1989

Histopathology

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One hundred benign and malignant primary liver tumours were screened immunocytochemically for alpha-fetoprotein (AFP), alpha 1-antitrypsin, alpha-human chorionic gonadotropin, carcinoembryonic antigen (CEA), keratin and vimentin. Alpha-fetoprotein was found in 16/63 (24%) hepatocellular carcinomas and in two hepatoblastomas. When comparing tissue positivity for AFP with tumour differentiation, grade 1 hepatocellular carcinomas were found to be negative, while 21% of grade 2, 36% of grade 3 and 16% of grade 4, respectively, stained positively. Alpha-fetoprotein positive cells were present in 9/10 hepatocellular carcinomas with serum levels exceeding 5000 ng/ml, but were absent in 17 tumours with serum AFP levels below 5000 ng/ml. All tumours other than hepatocellular carcinomas and hepatoblastomas were AFP negative. Carcinoembryonic antigen was present in 72% of cholangiocarcinomas, but was demonstrated in only one hepatocellular carcinoma. This exception was a combined hepatocellular-cholangiocarcinoma in which CEA expression was restricted to the cholangiocellular part. Alpha 1-antitrypsin was found in 4/63 hepatocellular carcinomas, in 2/2 fibrolamellar carcinomas and in 2/18 cholangiocarcinomas. Alpha-human chorionic gonadotropin was detected in one hepatocellular carcinoma and was strongly expressed in both fibrolamellar carcinomas. Weak staining for keratin was seen in most tumours with hepatocellular differentiation. All cholangiocarcinomas, in contrast, were strongly labelled with the keratin antibody. Co-expression of keratin and vimentin was observed in seven poorly differentiated hepatocellular carcinomas and three cholangiocarcinomas as well as in the two hepatoblastomas. The findings suggest that AFP is a diagnostic but rather insensitive immunocytochemical marker for hepatocellular differentiation in malignant liver tumours; CEA and keratin may help in discriminating cholangiocarcinomas from hepatocellular carcinomas.

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Section: Discussionmentioning

confidence: 82%

The significance of alpha‐fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours

Brumm

Schulze

Karina³

et al. 1989

Histopathology

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“…29,30 Structures resembling neurosecretory granules have been noticed in some 29 but not all ultrastructural studies. 1,31 The significance of this 'neuroendocrine differentiation' remains unclear, but is unlikely to be helpful in distinction from conventional HCC as up to one-fourth of the latter may also show 'neuroendocrine differentiation'. 30,32,33 Immunohistochemistry for AFP was negative in all cases tested, similar to other studies, 8 although focal positive reaction in small groups of cells has been reported.…”

Section: Discussionmentioning

confidence: 99%

“…30,32,33 Immunohistochemistry for AFP was negative in all cases tested, similar to other studies, 8 although focal positive reaction in small groups of cells has been reported. 31 Several studies have emphasized the better survival in fibrolamellar carcinoma compared to conventional hepatocellular carcinoma. 1,[3][4][5][8][9][10][11][12][13][14] However, these results could not be confirmed by many authors.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis

et al. 2005

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Fibrolamellar carcinoma arises in noncirrhotic livers of young individuals and has been considered to be less aggressive than conventional hepatocellular carcinoma. This study compares survival and clinicopathologic features of fibrolamellar carcinoma with hepatocellular carcinoma arising in noncirrhotic and cirrhotic livers. Clinical and pathologic features including age, gender, tumor size, stage and survival were recorded in 20 resected cases of fibrolamellar carcinoma. Survival was compared with resected hepatocellular carcinoma without (n ¼ 32) and with cirrhosis (n ¼ 30). Proliferative activity was determined by immunohistochemistry for Ki-67. In all, 12 (60%) patients with fibrolamellar carcinoma died during follow-up; the 5-year survival was 45%. Mortality in fibrolamellar carcinoma was higher with metastatic disease at presentation (6/7, 86% vs 5/13, 39%, P ¼ 0.06). Age, gender and tumor size did not correlate with survival. The 5-year (45 vs 56%, P ¼ 0.4) as well as overall survival (40 vs 56.3%, P ¼ 0.3) was similar in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis. The 5-year and overall survival in hepatocellular carcinoma with cirrhosis was 27 and 23.3%, respectively, which was not significantly different compared to fibrolamellar carcinoma (P ¼ 0.2). Among the cases without metastases at presentation, 5-year survival in fibrolamellar carcinoma (62%) and hepatocellular carcinoma without cirrhosis (57%) was significantly better (P ¼ 0.03) than hepatocellular carcinoma with cirrhosis (27%). The mean Ki-67 index was similar in all three groups (P ¼ 0.1). In conclusion, fibrolamellar carcinoma is an aggressive neoplasm with 45% 5-year survival and overall mortality of 60%. Nearly half the patients develop lymph node or distant metastasis. The prognosis of fibrolamellar carcinoma is similar to conventional hepatocellular carcinoma. Among nonmetastatic cases, the prognosis is better in fibrolamellar carcinoma and hepatocellular carcinoma without cirrhosis compared to hepatocellular carcinoma with cirrhosis. The better outcome in fibrolamellar carcinoma appears to be due to the absence of cirrhosis rather than its distinct clinicopathologic features.

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“…Thus, the bile canaliculi, or the propensity of hepatocytes to polarize with canalicular lumina in vitro , may be retained in cells of HCC origin. Examples of this phenomenon come from histological data on human HCC, as well from the different hepatic cell lines that were mentioned in earlier sections of this review, such as WIFB and HepG2, and Can10 cells (60, 113, 200, 226, 357). Moreover, certain pathways that promote hepatic polarization may incidentally be upregulated in hepatic carcinogenesis.…”

Section: Hepatic Polarity In Diseasementioning

confidence: 99%

Hepatocyte Polarity

Treyer

Müsch

2013

Comprehensive Physiology

250

266

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Hepatocytes, like other epithelia, are situated at the interface between the organism’s exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes.

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Fibrolamellár hepatocellular carcinoma. An immunohistochemical and ultrastructural study

Cited by 37 publications

References 19 publications

The significance of alpha‐fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours

The significance of alpha‐fetoprotein and other tumour markers in differential immunocytochemistry of primary liver tumours

Clinicopathologic features and survival in fibrolamellar carcinoma: comparison with conventional hepatocellular carcinoma with and without cirrhosis

Hepatocyte Polarity

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