The Diagnostic Role of α-smooth Muscle Actin in Superficial Invasive Laryngeal Squamous Cell Carcinoma

Abstract

Abstract Background Diagnosis of superficial invasion of laryngeal squamous cell carcinoma (LSCC) is a major challenge for pathologists as its confirmation is mainly based on histomorphologic features especially in presence of differentials and in absence of reliable diagnostic immunohistochemical markers. Despite focusing on study of tumor cells, the study of tumor microenvironment (TME) and its major component cancer associated fibroblasts (CAFs) will help to understand the participation of the tumor stroma in tumor development, progression and invasion differentiating it from other premalignant and benign lesions whose features may overlap with superficial invasive LSCC causing diagnostic dilemma. CAFs are characterized by the expression of α-smooth muscle actin protein (α-SMA) which represents the major component used to detect mesenchymal cells during process of TME. Objective To assess the diagnostic role of α-smooth muscle actin immunohistochemical expression in superficially invasive laryngeal squamous cell carcinoma. Methods The current study was conducted retrospectively on 108 cases of laryngeal biopsy samples as archived formalin fixed paraffin embedded blocks obtained from the Pathology Department lab of Ain Shams University Hospitals (Jan 2020-Dec 2022). The cases included in the current study were divided into 4 groups; Group 1: included 32 superficial invasive LSCC cases, Group 2: included 20 Laryngeal HGD/SIL cases, Group 3: included 36 PEH cases and Group 4: included 20 invasive LSCC cases. Data concerned with gender, age, lesion laterality, site and smoking history were obtained from the electronically archived reports. The histopathological data were re-examined microscopically by at least two authors. After then, the expression of Alpha SMA was evaluated in different groups, followed by statistical evaluation of the obtained results. Results Immunoreactivity of α-SMA was expressed in 87.5% of superficial invasive LSCC cases and 100% of invasive LSCC cases, while no reactivity was observed in all cases of HGD/SIL group, and rarely in PEH group (5.6%). There was statistically significant correlation between alpha SMA and both stroma changes and percentage of TILs in stroma of superficial invasive LSCC and no statistically significant relationship between alpha SMA expression and age, sex, lesion’s laterality, site, microscopic growth pattern, smoking, koiliocytic changes and hyperkeratosis in superficial invasive LSCC cases. The α-SMA expression pattern in stroma of superficial invasive LSCC was significantly different from that of HGD/SIL and PEH groups. Conclusion Alpha SMA is a potentially valuable marker for labelling CAFs and plays a reliable ancillary role in confirming the invasion for superficial invasive LSCC and differentiating it from HGD/SILs and PEH cases.