Fascin expression in progression and prognosis of hepatocellular carcinoma.
ABSTRACT Fascin is an actin-bundling protein and induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been reported to be associated with progression or prognosis in various neoplasms, but the role of fascin in hepatocellular carcinoma (HCC) remains unknown. The aim of this study was to investigate the clinicopathological and prognostic relevance of fascin by immunohistochemistry.
A total of 137 patients with HCC were stained with anti-fascin antibody. The tumor cells having unequivocal cytoplasmic and/or membranous fascin immunoreactivity were defined as fascin-positive.
Immunohistochemically, 23 (16.8%) HCCs having unequivocal fascin immunoreactivity were found. Tumors showing fascin expression were larger and less differentiated than those showing no fascin expression (P = 0.0239 and 0.0018, respectively). Portal venous invasion, bile duct invasion, and intrahepatic metastasis were detected significantly more frequently in fascin-positive group (P = 0.0029, 0.0333, and 0.0403, respectively). In addition, high alpha-fetoprotein (AFP) levels were significantly associated with the fascin expression in HCC (P = 0.0116). Fascin-positive group had significantly poorer outcomes than fascin-negative group and was an independent prognostic factor for disease-free survival.
Fascin might become a novel marker of progression in HCC and a significant indicator of a poor prognosis for patients with HCC.
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ABSTRACT: Recent studies have shown that the prognosis of recurrent hepatocellular carcinoma (HCC) after resection was dependent on the time of recurrence. The current study investigated whether early and late intrahepatic recurrences were associated with different risk factors and prognostic factors. After curative resection of HCC, 246 patients were followed prospectively for recurrence. Intrahepatic recurrences were classified into early (</= 1 year) and late (> 1 year) recurrences. Risk factors for recurrence and prognostic factors for survival after recurrence in each group were analyzed. Early and late intrahepatic recurrences developed in 80 patients and 46 patients, respectively. By multivariate analysis, preoperative tumor rupture (P = 0.022) and venous invasion (P < 0.001) were independent risk factors for early recurrence, whereas cirrhosis (P = 0.018) was the only significant risk factor for late recurrence. By comparing histologic features of resected recurrent and primary tumors, 8 of 9 resected early recurrent tumors (89%) were classified as intrahepatic metastases, whereas all 6 resected late recurrent tumors (100%) were multicentric occurrences. Despite similar treatments, the prognosis for patients with early recurrence was worse than that of patients with late recurrence (median survival of 15.8 months vs. 29.6 months; P = 0.005). Independent prognostic factors for early recurrence were serum albumin level and initial tumor pTNM classification, whereas only serum bilirubin level was found to be an independent prognostic factor for late recurrence. Early and late intrahepatic recurrences after resection of HCC were associated with different risk factors and prognostic factors. Early recurrences appear to arise mainly from intrahepatic metastases, whereas late recurrences are more likely to be multicentric in origin. The current study suggests that different strategies may be needed for the prevention and management of early and late recurrences. Further studies based on genetic analysis of clonal origins of tumors are required to clarify fully the mechanism of early and late recurrences after resection of HCC.Cancer 08/2000; 89(3):500-7. · 5.20 Impact Factor
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ABSTRACT: Fascin is an actin-bundling protein that induces membrane protrusions and cell motility after the formation of lamellipodia or filopodia. Fascin expression has been associated with progression or prognosis in various neoplasms; however, its role in intrahepatic cholangiocarcinoma is unknown. Tumor sections from 84 patients with intrahepatic cholangiocarcinoma and 16 patients with intrahepatic biliary dysplasia were stained with antifascin antibody. Fascin mRNA expression, measured by real-time reverse transcription-polymerase chain reaction in 20 frozen samples, was compared with the immunohistochemical results. Furthermore, the expression of cyclin D1 was compared with that of fascin. Immunohistochemically, fascin expression was absent or sporadic in normal biliary epithelium, whereas high expression (>70% of tumor cells) was found in 2 (12.5%) dysplasias and 30 (35.7%) intrahepatic cholangiocarcinomas. The difference between the fascin mRNA concentrations in the high-expression and low-expression groups was significant (P = .0082). Tumors showing high expression were poorly differentiated (P = .0019), and among poorly differentiated intrahepatic cholangiocarcinoma, larger tumors (>5 cm) were more likely than smaller lesions to have high fascin expression (P = .0205). A significant correlation was observed between fascin and cyclin D1 immunoreactivity (P = .0289). Patients whose tumors expressed fascin abundantly had a poorer outcome (P = .0085), and fascin overexpression was an independent prognostic factor (P = .0477). Fascin is expressed early in biliary carcinogenesis and might contribute to poor differentiation and to growth of intrahepatic cholangiocarcinoma. It is a significant indicator of a poor prognosis for patients with intrahepatic cholangiocarcinoma.Human pathology 10/2008; 40(2):174-80. · 3.03 Impact Factor
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ABSTRACT: The purpose of this study was to determine whether a relation does exist between clinicopathologic features and the prognosis of hepatocellular carcinoma (HCC) with respect to serum alpha-fetoprotein (AFP) levels at diagnosis. We reviewed the clinical data of 309 pathologically proven HCC cases divided into three groups: group 1 with normal AFP (<20 IU/mL), group 2 with moderately elevated AFP (20-399 IU/mL) and group 3 with markedly elevated AFP (> or =400 IU/mL). Of these, there were 76 (24.6%), 78 (25.2%), and 155 patients (50.2%) in groups 1, 2, and 3, respectively. We found that HCC patients with high AFP tended to have greater tumor size, bilobar involvement, massive or diffuse types, and portal vein thrombosis. Nonetheless, we could not establish a correlation between increased AFP and Okuda's stages, degree of tumor differentiation, or extrahepatic metastasis. The median survival rates in groups 1 (6 months) and 2 (7 months) were significantly longer than that of group 3 (3 months). On multivariate logistic regression analysis, positive hepatitis B surface antigen (HBsAg) status and bilobar tumor involvement represented the independent factors for predicting high AFP values. We concluded that AFP is useful not only for diagnosis, but also as a prognostic indicator in patients with HCC . However, it cannot be considered a sensitive tumor marker, particularly during the early stages in HBsAg-negative patients.Journal of Clinical Gastroenterology 12/2000; 31(4):302-8. · 3.20 Impact Factor