Tumminello Katherine, Hosler Gregory A
University of Mississippi Medical Center, Department of Pathology, Jackson, Mississippi.
ProPath, Division of Dermatopathology, Dallas, Texas.
J Cutan Pathol. 2018 May;45(5):318-324. doi: 10.1111/cup.13113. Epub 2018 Mar 1.
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.
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).
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).
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.
Wnt信号通路与毛母质瘤的发病机制有关。淋巴样增强因子结合因子1（LEF-1）是该信号通路的下游成分，尾型相关同源框转录因子2（CDX2）被推测可对其进行调控，但关于这些转录因子在毛母质瘤中的表达情况知之甚少。
对12例毛母质瘤（PMs）、12例毛母质癌（PMCAs）和18例非毛母质皮肤肿瘤进行CDX2、β-连环蛋白、LEF-1、细胞角蛋白19（CK19）、细胞角蛋白5（CK5）、富含AT序列结合蛋白2（SATB2）、钙黏蛋白17和雄激素受体的免疫组化检测。
PMs和PMCAs中CDX2呈阳性（9/12例PMs，敏感性=75%，特异性=100%；11/12例PMCAs，敏感性=92%，特异性=100%；P<0.01），β-连环蛋白呈阳性（12/12例PMs，敏感性=100%；特异性=94%；10/12例PMCAs，敏感性=83%，特异性=94%；P<0.01），LEF-1呈阳性（12/12例PMs，敏感性=100%，特异性=56%；12/12例PMCAs，敏感性=100%，特异性=56%；P<0.01）。CDX2表达通常呈局灶性，存在于离散的鳞状细胞亚群中。LEF-1的表达模式有所不同，在毛母质瘤（强、弥漫性）和非毛母质瘤（弱、斑片状）之间可辨别。
本研究再次证实Wnt信号通路在毛母质瘤发生中的重要性，并将CDX2引入作为毛母质瘤发生的可能调节因子和标志物。考虑到表达模式，LEF-1和CDX2作为PMCA的诊断标志物，其表现至少与β-连环蛋白一样好，甚至可能更好，在诊断不明确的原始外观皮肤肿瘤时应予以考虑。
