CDX2 and LEF-1 expression in pilomatrical tumors and their utility in the diagnosis of pilomatrical carcinoma

Abstract

Background: The Wnt signaling pathway has been implicated in the pathogenesis of pilomatrical tumors. Lymphoid enhancer-binding factor 1 (LEF-1) is a downstream component of this pathway, and Caudal-related homeobox transcription factor 2 (CDX2) has been postulated to regulate it, but little is known about expression of these transcription factors in pilomatrical tumors.

Methods: Immunohistochemistry for CDX2, β-catenin, LEF-1, CK19, CK5, Special AT-rich sequence- binding protein 2 (SATB2), cadherin 17 and androgen receptor was performed on pilomatricomas (PMs) (N = 12), pilomatrical carcinomas (PMCAs) (N = 12) and non-pilomatrical cutaneous tumors (N = 18).

Results: PMs and PMCAs were positive for CDX2 (9/12 PMs, sensitivity = 75%, specificity = 100%; 11/12 PMCAs, sensitivity = 92%, specificity = 100%; P < 0.01), β-catenin (12/12 PMs, sensitivity = 100%, specificity = 94%; 10/12 PMCAs, sensitivity = 83%, specificity = 94%; P < 0.01) and LEF-1 (12/12 PMs, sensitivity = 100%, specificity = 56%; 12/12 PMCAs, sensitivity = 100%, specificity = 56%; P < 0.01). CDX2 expression was commonly focal, within a discrete subpopulation of squamoid cells. The LEF-1 expression pattern was different and discernable between pilomatrical tumors (strong, diffuse) and non-pilomatrical tumors (weak, patchy).

Conclusion: This study reaffirms the importance of the Wnt signaling pathway in the tumorigenesis of pilomatrical tumors, and this introduces CDX2 as a possible regulator and marker of pilomatrical tumorigenesis. LEF-1 and CDX2 performed at least as well as β-catenin, if not better when taking into account expression pattern, as a diagnostic marker for PMCA, and should be considered in the workup of ambiguous primitive-appearing cutaneous tumors.

Keywords: CDX2; LEF-1; pilomatrical carcinoma; pilomatricoma.