The apoptotic paradox in retinoblastoma.

The purpose of this study was to investigate the clinicopathological features and the expression of proteins involved in cell proliferation and the different pathways of apoptosis in retinoblastoma. Nineteen retinoblastoma patients were included, and mitotic index (MI) and apoptotic index (AI) were assessed. The expression of MIB-1, p53, caspase-3, Bcl-2, and Fas protein was assessed by immunohistochemistry. Mann-Whitney U test and Fisher's exact test were used for statistical comparison. High MI (mean 16.84, range 0-66) and high MIB-1 expression (mean 57.89, range 0-90) were found. The MI was significantly related to MIB-1 expression (P= 0.01). The tumors showed a high apoptotic index (mean 40.26, range 1-110), and the AI was associated with the mitotic index (P= 0.02). The caspase-3 expression was positively related to the AI (P= 0.03), although a small number of tumors with no significant or very low caspase-3 staining showed a high number of apoptotic cells, suggestive of a caspase-3-independent apoptosis pathway. Bcl-2 expression was not significantly related to AI (P= 0.07). No striking relationship was found in expression patterns of p53, Bcl-2, caspase-3, and Fas. In conclusion, we found that (1) cell proliferation and apoptosis are linked in retinoblastoma; (2) activation of effector caspase-3 induces apoptosis in retinoblastoma, but Bcl-2 overexpression does not prevent apoptosis in many tumors; (3) there is a p53-independent pathway in approximately one-quarter of cases; (4) the findings suggesting a caspase-3-independent pathway might lead to apoptosis in retinoblastoma; and, finally, we found no consistent pattern of expression of apoptotic and antiapoptotic molecules, suggesting that in retinoblastoma there is no preference for any single pathway of apoptosis. Confirmation of the results in a large set of tumors would be useful.

Hepatoid carcinoma of the gallbladder.

Hepatoid carcinoma is a special type of extrahepatic tumor associated with hepatic differentiation, and has the morphological and functional features of hepatocellular carcinoma. Hepatoid carcinoma of the gallbladder is very rarely reported in the literature. We report a case of hepatoid carcinoma of the gallbladder in a 71-year-old female who presented with abdominal pain and was first diagnosed as cholelithiasis with cholecystitis. The microscopic findings of the gallbladder after cholecystectomy showed an area of tumor with polygonal cells, eosinophilic cytoplasm, distinct cell borders, round vesicular nuclei and prominent nucleoli, arranged in trabecular pattern resembling hepatocellular carcinoma intermingled with areas of adenocarcinoma or cholangiocarcinoma. The specimen from the pancreas also showed the same type of tumor cells. Histochemically, some of tumor cells were positive for Victoria Blue, Stein, and PAS. The immunohistochemistry for alpha-fetoprotein (AFP) showed strong intra cytoplasmic positivity, both in tumor cells with hepatic differentiation and tumor cells with bile duct epithelium differentiation. Based on these findings, this case was diagnosed as hepatoid carcinoma of the gallbladder with metastasis to the pancreas. This is the first case that has been reported in our department.