Tissue Expression of Carbonic Anhydrase IX Correlates to More Aggressive Phenotype of Basal Cell Carcinoma

Daniela Russo,Francesco Merolla,Rosa Maria Di Crescenzo,Claudia Costa,Francesco Martino,Sara Pignatiello,Silvia Varricchio,Gennaro Ilardi,Stefania Staibano,Massimiliano Scalvenzi,Massimo Mascolo

doi:10.3389/fonc.2021.659332

Daniela Russo, Francesco Merolla + Show 9 more

Open Access

https://doi.org/10.3389/fonc.2021.659332

Copy DOI

Abstract

Basal cell carcinoma (BCC) is the most common cancer in the white-skinned population accounting for about 15% of all neoplasms. Its incidence is increasing worldwide, at a rate of about 10% per year. BCC, although infrequently metastasizing, very often causes extensive tissue losses, due to the high propensity toward stromal infiltration, particularly in its dedifferentiated forms, with disfiguring and debilitating results. To date, there still is limited availability of therapeutic treatments alternative to surgery. We evaluated the immunohistochemical expression of the carbonic anhydrase IX (CAIX), one of the main markers of tissue hypoxia, in a set of 85 archived FFPE BCC tissues, including the main subtypes, with different clinical outcomes, to demonstrate a possible relationship between hypoxic phenotype and biological aggressiveness of these neoplasms. Our results showed that the expression level of the CAIX protein contributes to the stratification of BCC in the different risk classes for recurrence. We hypothesize for CAIX a potential therapeutic role as a target therapy in the treatment of more aggressive BCCs, thus providing an alternative to surgical and pharmacological therapy with Hedgehog inhibitors, a promising example of target therapy in BCCs.

Highlights

Basal cell carcinoma (BCC) is defined by the World Health Organization (WHO) as a locally invasive, slow-growing tumor that originates from the basal layer cells of the epidermis, placed peripherally to the hair bulbs, and that rarely hesitates in metastasis
In the context of non-melanoma skin cancer (NMSC), BCC accounts for about 80% of the cases [3], with a global incidence increase of 3% to 7%/year over last decades [4], BCC represents a serious public health problem
Among the molecules most expressed in hypoxia condition are HIF-1 a and carbonic anhydrase IX (CAIX)

Summary

Introduction

Basal cell carcinoma (BCC) is defined by the World Health Organization (WHO) as a locally invasive, slow-growing tumor that originates from the basal layer cells of the epidermis, placed peripherally to the hair bulbs, and that rarely hesitates in metastasis. CAIX belongs to the family of Carbonic Anhydrases (CA), a group of metal zinc-containing enzymes that catalyze the reversible hydration of CO2 in HCO3 and H + ions and has recently emerged as the most promising endogenous marker of cellular hypoxia [10, 11] This reaction is fundamental at the level of cells, tissues, and organs in a wide range of biochemical and physiological processes such as acid-base equilibrium, gas exchange, ionic transport, and carbon dioxide fixation. We deepened the role of the Carbonic Anhydrase IX as a possible leading actor and marker of hypoxia in BCC, by evaluating the immunohistochemistry expression of the CAIX protein in a series of archived FFPE BCC tissue samples

Methods

Results

Conclusion