Expression of Hedgehog signalling molecules in microcystic adnexal carcinoma

Abstract

Background. Microcystic adnexal carcinoma (MAC) is a rare skin neoplasm that has not been characterized on a molecular basis. Aim. To assess expression profiles of Hedgehog (HH) signalling molecules in MAC and control tumours. Methods. Immunohistochemistry was performed for Sonic Hedgehog (SHH), Indian Hedgehog (IHH), Patched 1 (PTCH1) and Smoothened (SMO) on patient MAC tissue (n = 26) and control tumour tissue, including syringoma (SyG; n = 11), trichoepithelioma (TE; n = 11) and basal cell carcinoma (BCC; n = 12) tissues. Results. Patched 1 and SMO immunoreactivity was significantly higher in BCC than in SyG, TE or MAC (P < 0.001 and P < 0.03, respectively). The highest IHH expression was observed in BCC and TE compared with SyG and MAC (P < 0.04). Notably, the highest SHH protein expression was observed in SyG compared with MAC, TE and even BCC (P < 0.001). In patients with MAC, SMO immunoreactivity significantly (r = 0.51; P < 0.01) correlated with PTCH1 expression. Further correlation studies did not show significant associations between the HH expression markers assessed (P > 0.05). Conclusion.Our results indicate that alterations of the HH signalling are unlikely to play a major role in the pathogenesis of MAC, which is in contrast to the morphologically similar BCC and TE. Our observation provides additional information to the limited molecular pathology knowledge on this rare tumour.

Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors

“…These data were consistent with another study in which sequencing indicated a mutation of TP53 with loss of CDKN2A and CDKN2B in metastatic MAC [74]. Another study reported that, unlike basal cell carcinoma, Hedgehog signaling was not significantly altered in MAC [75]. Considering its lack of UV signature and since no oncogenic mutation was identified in one third of the cases in the largest study to date, more studies are required, including the detection of gene fusions, to reveal the genomic landscape of MAC.…”