Expression of Heat Shock Protein 105 in Cutaneous Squamous Cell Carcinoma: Correlation with Clinicopathological Characteristics

Abstract

Background Heat shock proteins (HSPs), a group of heat stress proteins, are characterized by highly conserved properties. Malignant transformation is a cellular stress, and the expression of HSPs may be affected during this process. Heat shock protein 105 (HSP105) is a protective protein that has long been observed in many cancer types, but little attention has been given to cutaneous squamous cell carcinoma (CSCC). As such, the objectives of this study were to observe the expression of HSP105 on CSCC and evaluate its correlation with clinicopathological characteristics. Methods This retrospective study enrolled 60 patients with CSCC. The patients’ clinical data, including sex, age, tumor location, tumor type, and degree of pathological differentiation, were collected. The expression of HSP105 was measured by Western blot and immunohistochemical staining. Results HSP105 expression was decreased in CSCC (HSCORE=0.65 (0.30, 1.98)) compared with normal skin (HSCORE=2.20 (1.50, 2.80)) (P<0.001). These results were consistent with the Western blot analysis. HSP105 immunostaining of Bowen disease (HSCORE=1.28 (1.08, 2.40)) revealed higher expression than in verrucous carcinoma (HSCORE=0.30 (0.23, 0.85)), keratoacanthoma (HSCORE=0.53 (0.29, 0.93)) and acantholytic squamous cell carcinoma (HSCORE=0.53 (0.41, 0.68) (P<0.01)). Poorly differentiated CSCC showed significantly higher expression of HSP105. Conclusion Our study reveals for the first time that the expression of HSP105 is decreased in CSCC. We suggest that the molecular mechanisms underlying the differential expression of HSP deserve a more rigorous future study, the results of which might explain its role in carcinogenesis and its potential as a target for selective tumor therapy.

The Contributions of Cancer-Testis and Developmental Genes to the Pathogenesis of Keratinocyte Carcinomas

“…Contrary to dogma, CTA expression is biased to gametes and cancer cells, but not restricted to them. Several CTAs, including brother of the regulator of imprinted sites (BORIS), piwi-like RNA mediated gene silencing 2 (PIWIL2) and heat shock protein 105 (HSP105) are expressed at low levels in healthy epidermal keratinocytes [ 97 , 98 , 99 , 100 ]. Their expression levels are altered in cancer (these CTAs are excluded from Table 1 ).…”

“…Loss of BORIS in keratinocytes is also linked to increased genomic instability and proliferation [ 100 ]. In contrast, HSP105, a stress-responsive chaperone, is overexpressed in poorly differentiated cSCC tumors and metastases [ 98 , 99 ]. These observations are interesting for at least two reasons.…”

“…On the other hand, overexpression of protective factors may foster more treatment-resistant cancer cells. HSP105 overexpression is observed in 100% of cSCC metastases and correlates with high tumor grade [ 98 , 99 ]. In vitro studies illustrate that HSP105 expression can confer a selective growth advantage to cSCC cells [ 98 ].…”

“…HSP105 overexpression is observed in 100% of cSCC metastases and correlates with high tumor grade [ 98 , 99 ]. In vitro studies illustrate that HSP105 expression can confer a selective growth advantage to cSCC cells [ 98 ]. Studying the significance of CTA expression in non-neoplastic and pre-neoplastic epidermis may yield insights into designing targeted chemoprevention or in predicting cancer development.…”