Difference in transducin-like enhancer of split 1 protein expression between basal cell adenomas and basal cell adenocarcinomas - an immunohistochemical study

Yuzo Oyama, Haruto Nishida, Takahiro Kusaba, Hiroko Kadowaki, Motoki Arakane, Junpei Wada, Shogo Urabe, Takashi Hirano, Kenji Kawano, Masashi Suzuki, Shigeo Yokoyama, Tsutomu Daa

Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are benign and malignant, basaloid salivary gland neoplasms, respectively. These tumors show a dual-cell proliferation of inner luminal/ductal cells and outer abluminal/myoepithelial or basal cells. The only difference between them is defined as a malignant morphology such as invasion. Recently, the nuclear expression of β-catenin and a catenin beta-1 (CTNNB1) mutation were found in BCA. Transducin-like enhancer of split 1 (TLE1) belongs to the Groucho/TLE family, and it functions in the "off" state in the Wnt/β-catenin signaling pathway. We hypothesized that if the dysregulation of the Wnt/β-catenin signaling pathway could be attributed to the tumorigenesis of BCA/BCAC, there might be differences in TLE1 expression between BCA and BCAC. The study included 35 BCA and 4 BCAC cases. We performed immunohistochemistry to detect TLE1 and β-catenin and investigated the catenin beta-1 (CTNNB1) mutational profile among BCA and BCAC cases. In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of β-catenin in abluminal cells. The BCA cases harbored CTNNB1 gene mutations (12/35). In BCAC, luminal cell staining of TLE1 was identical to BCA in non-invasive areas (4/4) but indistinct in invasive areas (3/4). The BCAC cases were β-catenin positive for abluminal cells in both areas. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. Immunohistochemical analysis for TLE1 can identify BCA and BCAC by luminal cell staining difference, especially indistinct luminal cell expression for TLE1 in invasive areas of BCAC. Moreover, TLE1 can be luminal/ductal cell markers.