LEF1 – Antibody Lexicon

Synonyms: Lymphoid enhancer binding factor 1, LEF-1, TCF10, TCF7L3, TCF1ALPHA

by Jan Klos

Background

The protein encoded by LEF1 gene is a transcription factor involved in the Wnt pathway. It is expressed in pre-B and T cells. It can bind to a functionally important site in the T-cell receptor-alpha enhancer. It is involved in in hair cell differentiation and follicle morphogenesis. Probably involved also in development of submucosal glands in trachea and bronchi, mammary glands and teeth. Mutations are often found in sebaceous tumors. The gene is linked also to other cancers, including androgen-independent prostate cancer. Aberrant expression of LEF1 is implicated in tumorigenesis and cancer cell proliferation, migration, and invasion.

Expression in normal tissues

Expression in normal tissues is seen in lymph nodes (highest), but also in appendix, testis and spleen are most often positive. Positive staining is also seen in adrenals, placenta, endometrium, bone marrow, prostate, urinary bladder, lung, gallbladder and to lesser extend in some other organs.

Expression in tumors

Reported as high as 80-100% cases in the following tumors:

hair follicle derived tumors
solid pseudo papillary tumor of pancreas
basal cell adenoma and pleomorphic adenoma of salivary gland (but only in single cases of adenoid cystic carcinoma)
cribriform-morular variant of papillary carcinoma of thyroid (but in less than 20% of classic papillary carcinomas of thyroid)
squamous cell carcinoma of esophagus (adenocarcinoma is usually negative)
chronic lymphocytic leukemia/small lymphocytic lymphoma (but rarely in other small cell lymphomas), positive staining correlates with poorer prognosis of atypical variant
malignant melanoma

Gastro-intestinal adenocarcinomas only infrequently stain for LEF1 with the exception of colorectal carcinomas (around 40% positive). Positive staining in metastatic setting may support the colorectal origin of adenocarcinoma, especially that these tumors are often negative for CK20, CDX2. Moderate to strong LEF1 positive nuclear staining used to correlate with poorer prognosis as compared to LEF1 negative colorectal tumors.

Staining pattern

There are reports of focal, nonspecific staining with peripheral accentuation in cytoplasm of basal cell adenoma and pleomorphic adenoma of salivary glands.

Control tissue

Diagnostic application

Differentiation between adenoid cystic carcinoma (negative) and its potential mimics (positive) in salivary glands
Confirming cribriform-morular variant of papillary carcinoma of thyroid
Supporting diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma
Supporting diagnosis of solid pseudo papillary tumor of pancreas (positive) against pancreatic neuroendocrine tumors (negative)
Positive staining in DLBCL may suggest that it is more likely a result of Richter`s transformation than primary DLBCL

by Jan Klos

Background

Expression in normal tissues

Expression in tumors

Staining pattern

Control tissue

Selected references