Hedgehog Components Are Present in Polymorphous Adenocarcinoma of the Salivary Gland Regardless of PRKD1 Mutation and Tissue Invasion.

Purpose: Polymorphous adenocarcinoma of the salivary gland is characterized by cellular uniformity associated with a variety of morphological growth patterns, a fact that makes its diagnosis challenging. Therefore, the identification of genetic alterations and signaling pathways emerges as a tool for elucidation of the pathogenesis of this tumor and accurate differential diagnosis. The aim of this study was to assess mutations in the PRKD1 gene and in protein components of the HH pathway (SHH, IHH, SMO, and GLI-1) in cases of polymorphous adenocarcinoma of the salivary gland.

Methods: Sanger sequencing was used to interrogate hotspot mutations in PRKD1 exon 15 and immunohistochemistry to analyze the protein expression of PRKD1, SHH, IHH, SMO, and GLI-1.

Results: The PRKD1 c.2130A>C/T hotspot mutation was detected in 50% of the sequenced samples. A previously unreported variant, c.2110C>T resulting in p.His704Tyr, was identified in one case, while 100% of the samples carried the intronic variation rs2273813, regardless of tissue invasion (perineural, lymphovascular, fat, bone, muscle, and mucous acini). Immunostaining revealed significant results for several associations between PRKD1, IHH, SMO, and GLI-1. In contrast, SHH immunoexpression did not correlate with the expression of the other proteins.

Conclusion: The PRKD1 E710D hotspot mutation and protein expression of PRKD1 and HH components (SHH, IHH, SMO, and GLI-1) were detected in PAC regardless of tissue invasion, although HH proteins contributed to the morphogenesis of this rare oral cancer. Additionally, the positive correlation between the expression of PRKD1 and HH pathway components (IHH, SMO, and GLI-1) suggests a possible interaction between these proteins, independent of the HH pathway ligand.