Early precursor of mixed endocrine-exocrine tumors of the gastrointestinal tract: histologic and molecular correlations.

BACKGROUND: Mixed endocrine-exocrine tumors display histologic features of endocrine and glandular differentiation. Unlike in collision tumors, the two components are thought to arise from a monoclonal precursor. Evidence from molecular testing supports the monoclonal theory and suggests that the exocrine component may give rise to the endocrine component but not vice versa. CASE REPORT: We report a case of an adenomatous polyp in the large intestine that had groups of endocrine cells arising from the crypt bases of the adenomatous (exocrine) epithelium. To our knowledge, ours is only the second report of an adenomatous polyp in which groups of microcarcinoid endocrine cells were recognized. The histologic findings in our case correlate with the molecular findings described in mixed endocrine-exocrine tumors. CONCLUSION: Our description may represent the primordial stage of a mixed endocrine-exocrine neoplasm.

LEF-1 is frequently expressed in colorectal carcinoma and not in other gastrointestinal tract adenocarcinomas: an immunohistochemical survey of 602 gastrointestinal tract neoplasms.

LEF-1 is a DNA-binding protein that interacts with ß-catenin and activates Wnt-responsive target genes. We analyzed the immunohistochemical expression of LEF-1 in 602 gastrointestinal and pancreatobiliary neoplasms in an attempt to (1) investigate the utility of LEF-1 immunohistochemistry as an ancillary marker in gastrointestinal/pancreatobiliary neoplasia, and (2) to perform a clinicopathologic and survival analysis of colorectal carcinoma stratified by LEF-1 expression. LEF-1 nuclear positivity was frequently identified in colorectal carcinoma (89/241, 37%) and only infrequently identified in other neoplasms: 11% esophagus/esophagogastric adenocarcinomas, 7% gastric adenocarcinomas, 1% pancreatic ductal adenocarcinomas, 4% pancreatic intraductal papillary mucinous neoplasms, and in no cases of appendiceal mucinous neoplasms or pancreatic mucinous cystic neoplasms. LEF-1 expression was identified in 35% of colorectal carcinomas that lacked CK20 and CDX2 expression. In colorectal carcinomas, LEF-1-positive tumors more frequently harbored KRAS mutations compared with LEF-1-negative tumors (39% vs. 16%, P=0.005). Patients with moderate/strong LEF-1-positive colorectal carcinoma had a trend of worse overall survival compared with patients with colorectal carcinomas with weak/negative LEF-1 expression (5 y overall survival, 31% vs. 47%, P=0.15). In conclusion, LEF-1 is most commonly expressed in colorectal carcinoma and infrequently observed in the upper gastrointestinal tract and pancreatic adenocarcinoma. LEF-1 Immunohistochemistry may be especially useful as an ancillary diagnostic marker in colorectal carcinomas, which lack the expression of both CK20 and CDX2. LEF-1 expression is associated with the presence of KRAS mutations and may have prognostic value as a trend of worse overall survival is seen in patients with LEF-1-positive colorectal carcinoma.