The Bcl‐xL inhibitor of apoptosis is preferentially expressed in cutaneous squamous cell carcinoma compared with that in keratoacanthoma

Abstract

Keratoacanthoma (KA) is difficult to histologically distinguish from squamous cell carcinoma (SCC). Therefore, although KA is a benign self‐resolving skin lesion, KA is commonly treated as SCC. Biomarkers to distinguish KA and SCC would thus be desirable. In search for specific markers, paraffin‐embedded tissue samples from 25 SCC and 64 KA were arranged in a tissue microarray (TMA) and stained for immunologic cell‐markers CD3, CD20 and CD68 as well as for proteins considered of relevance in tumorgenesis, namely NFκB/p65, IκB‐α, STAT3, p53, TRAP‐1, pRB, phosphorylated pRb, Cyld, p21, p16INK4, Survivin, Bcl‐xL, Caspase 3, Bak, FLK‐1/VEGF‐r2 and Ki‐67. In addition, the tumors were tested for presence of human papillomavirus by PCR. We detected that the two lesions differed significantly in expression of Bcl‐xL which was present in 84% of the SCC compared with only 15% in the KA (p < 0.001). The lower expression of the antiapoptotic protein Bcl‐xL in KA is consistent with a possible role of apoptosis in the regression of KA. © 2008 Wiley‐Liss, Inc.

Array Comparative Genomic Hybridization of Keratoacanthomas and Squamous Cell Carcinomas: Different Patterns of Genetic Aberrations Suggest Two Distinct Entities

“…Candidates for such genes may be found within amplifications on chromosome X (e.g., apoptosis-inducing factor 1 and tumor necrosis factor receptor superfamily) and within amplifications on chromosome 20 (e.g., Bcl-X, death associated transcription factor 1, and retinoblastoma protein 1). The anti-apoptotic Bcl-xL protein was found to be present in 84% of SCCs compared with only 15% in KAs (Po0.001) (Vasiljevic et al, 2009), suggesting a possible role for the anti-apoptotic Bcl-xL protein for progression and lack of regression in SCCs, and for a possible role of apoptosis in the regression of KA.…”

Keratoacanthoma and squamous cell carcinoma are distinct from a molecular perspective

“…23 Another study examined keratoacanthomas showed lower expression of the anti-apoptotic protein Bcl-xL that is consistent with a possible role of apoptosis in keratoacanthoma regression. 24 BCL-2 is a proto-oncogene involved in protecting cells from undergoing apoptosis and has been shown to have decreased expression in regressing keratoacanthomas. 23,25 We hypothesize that prominent enrichment of the clathrin-mediated endocytosis signaling pathway may be because of granzyme-mediated apoptosis.…”

Histogenesis of keratoacanthoma: histochemical and immunohistochemical study

“…7,47,48 There are several reports of differential expression of molecular markers, such as laminin-32, nuclear factor kappa B/p50, cortactin, glut-1, Bcl-x, beta-catenin, CD44, anti-P2 X7, K10, E-cadherin, transforming growth factor-a, peanut agglutinin, peanut lectin receptor, and carcinoembryonic antigen, in KAs and SCCs. 22,31,40,43,44,[49][50][51][52][53][54][55][56][57][58][59][60][61][62] KAs were consistently positive for K6, K10, and K14. K10 and K14 were observed in specialized cells within the ORS of the hair follicle and in the interfollicular epithelium.…”