Analysis of Novel Immunohistochemical Markers and Genetic Pathways in Mixed Carcinomas of the Pancreas
F Bao, M Arcila, J Garcia, E Stelow, R Hruban, DS Klimstra. Memorial Sloan-Kettering Cancer Center, New York, NY; University of Virginia Health System, Charlottesville, VA; Johns Hopkins University, Baltimore, MD
Background: Mixed pancreatic carcinomas have significant elements of more than one line of differentiation. Because of their rarity, mixed carcinomas raise many problems in diagnosis, management and therapy. The pathogenesis of these tumors is poorly understood.
Design: We collected 21 cases of mixed carcinomas of the pancreas, including 13 acinar-ductal carcinomas, 6 acinar-endocrine carcinomas and 2 ductal-endocrine carcinomas. Most of the mixed carcinomas (19 of 21, 91%) expressed markers of acinar differentiation in >25% of the tumor cells. Immunohistochemical analysis using novel pancreatic epithelial markers (maspin and mesothelin) and stromal marker (fascin) as well as CK19, p53, DPC4 and b-catenin was performed on paraffin-embedded tissues. KRAS mutations were analyzed by direct sequencing.
Results: Twenty out of 21 mixed carcinomas (95%) expressed CK19 in 40-100% of the tumor cells. Focal expression of maspin and mesothelin (10-40%) was infrequently observed in mixed carcinomas (4/21 and 2/21, respectively). More than half of mixed carcinomas (11/21) showed focal expression of fascin (5-15%). Interestingly, two of 6 mixed acinar-endocrine carcinomas (33%) had strong cytoplasmic fascin and nuclear b-catenin expression in more than 30% of the tumor cells. This finding supports a correlation between b-catenin abnormality and fascin expression. KRAS mutations were identified in 1 ductal-endocrine and 2 acinar-ductal carcinomas, one of which also showed p53 expression by immunohistochemistry. The loss of DPC4 was found in 1 mixed acinar-ductal and 1 ductal-endocrine carcinoma. Detailed immunohistochemical results are listed in the table.
|Tumor/marker||CK19||maspin||mesothelin||fascin||b-catenin||p53||loss of DPC4|
Conclusions: The fact that mixed carcinomas of the pancreas universally expressed CK19 but infrequently expressed the terminally differentiated ductal markers (maspin and mesothelin) indicates that they resemble protodifferentiated epithelial cells with features of ductal cells. Our study shows that, in contrast with conventional ductal adenocarcinoma, KRAS, p53, and DPC4 are rarely involved in the pathogenesis of the mixed tumors that predominantly express acinar differentiation.
Category: Liver & Pancreas
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 239, Wednesday Morning