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 β-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.
*Department of Pathology, University of Pittsburgh Medical Center, Presbyterian Hospital, Pittsburgh, PA †Department of Radiation Oncology, Stanford University, Stanford, CA.
Taher R
TR
Kermanshahi
Priya
P
Jayachandran
Daniel T
DT
Chang
Reet
R
Pai
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D000071616:CDX2 Transcription Factor; D002467:Cell Nucleus / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000401:mortality; D003937:Diagnosis, Differential; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D053554:Keratin-20 / Q000378:metabolism; D051821:Lymphoid Enhancer-Binding Factor 1 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011379:Prognosis; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D014408:Biomarkers, Tumor; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D018398:Homeodomain Proteins; C117307:KRAS protein, human; C507499:KRT20 protein, human; D053554:Keratin-20; C497573:LEF1 protein, human; D051821:Lymphoid Enhancer-Binding Factor 1; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins