Pilomatrix carcinomas contain mutations in CTNNB1, the gene encoding β‐catenin

Abstract

Mutations in beta-catenin are present in benign pilomatrixomas. beta-catenin is a downstream effector in the WNT-signalling pathway, acting as a signal for differentiation and proliferation. Mutations in CTNNB1, the gene encoding beta-catenin, are present in a wide variety of benign and malignant neoplasms. We examined beta-catenin in a series of pilomatrix carcinomas (15 cases) by using immunohistochemistry and DNA sequencing of exon 3 from CTNNB1, and compared these to a series of benign pilomatrixomas (13 cases). All 11 pilomatrix carcinomas available for examination showed nuclear localization of beta-catenin and mutations in exon 3 similar to those demonstrated in benign pilomatrixomas. Two of 11 pilomatrix carcinomas showed significant nuclear accumulation of p53, whereas this was absent in all 13 benign pilomatrixomas. Expression of nuclear cyclin D1 was similar in both benign pilomatrixomas and pilomatrix carcinomas. Clinical follow-up from the 15 malignant cases reported in this study and by others indicates that wide excision offers superior control of local recurrence, compared to simple excision. Immunohistochemical and molecular analysis of beta-catenin reveals that both pilomatrix carcinomas and benign pilomatrixomas harbour mutations in beta-catenin. This implies a common initial pathogenesis and is compatible with the proposition that pilomatrix carcinomas may at least on occasion arise from their benign counterparts.

Nuclear β-Catenin Expression is Frequent in Sinonasal Hemangiopericytoma and Its Mimics

“…CTNNB1 alterations in sinonasal HPC have been consistently reported in exon 3, with missense mutations [4,5]; mutations affecting positions 32-45 of the amino-terminal region disrupt phosphorylation-dependent degradation of b-catenin [6]. Numerous other tumor types harbor CTNNB1 mutations, most frequently desmoid-type fibromatosis [7,8] as well as salivary basal cell adenoma [9], pilomatricoma and pilomatrix carcinoma [10], hepatocellular carcinoma [11], colorectal carcinoma [12], medulloblastoma [13], endometrial adenocarcinoma [14], Wilms tumor [15], and adrenocortical carcinoma [16]. Sinonasal HPC shares the features of a uniform spindle and ovoid cell population and HPC-like vessels with SFT, Fig.…”

Vulvar Adnexal Lesions: A 32-Year, Single-Institution Review From Massachusetts General Hospital

“…51 Mutations in exon 3 of the CTNNB1 (b-catenin) gene have been documented in pilomatricoma, pilomatrical carcinoma, and BCC with matrical differentiation. 52,53 We identified 2 of the 56 malignant cases (4%) of pilomatricoma in our series.…”

“Tumour Perplex” called pilomatricoma — Report of a case with confounding chest wall mass in an adult male and its literature review

“…Although local trauma, folliculitis or insect bites are considered as likely initiative factors, their precise role in the pathogenesis still remains blurred [5]. Nonetheless, recent research has highlighted a persuasive role of certain mutations (CTNNB1) in the β-catenin pathway towards its tumorigenesis [6][7][8].…”