Increased Toll-like receptor 9 expression associated with cellular proliferation and poor prognosis in pleural mesothelioma

BACKGROUND: Pleural mesothelioma is an aggressive malignancy with a poor prognosis. The epithelioid subtype is the most common and can be challenging to distinguish from metastatic lung adenocarcinoma (MLAC). The role of Toll-like receptor 9 (TLR9) in the progression of pleural mesothelioma remains unclear. METHODS: A total of 30 pleural biopsy specimens were collected, comprising 10 cases of pleural epithelioid mesothelioma and 20 cases of MLAC. The mRNA expression levels of TLR9 and proliferating cell nuclear antigen (PCNA) were quantified. In addition, sixty archived formalin-fixed, paraffin-embedded tissue blocks (40 epithelioid mesothelioma and 20 MLAC) were analyzed via immunohistochemistry using an anti-TLR9 antibody in relation to various clinicopathological parameters. RESULTS: TLR9 expression was significantly higher in epithelioid mesothelioma cases than in MLAC cases (p < .001), with mean values of 1.54 ± 0.09 and 1.02 ± 0.08, respectively. A significant positive correlation was observed between TLR9 and PCNA expression levels specifically in the epithelioid mesothelioma cohort (p < .001, r = 0.8). Furthermore, immunohistochemical analysis confirmed that high TLR9 immunoexpression was significantly more prevalent in epithelioid mesothelioma (36/40 cases; 90%) than in MLAC (3/20 cases; 15%) (p < .001). Notably, elevated TLR9 expression was associated with a significantly shorter overall survival (p = .001). CONCLUSIONS: In conclusion, TLR9 expression is significantly elevated in epithelioid mesothelioma compared to MLAC at both the molecular and cellular levels, and its expression correlates with increased tumor proliferation and poorer prognosis. Our data suggest that TLR9 could represent a promising diagnostic and prognostic biomarker, warranting further investigation into its potential therapeutic applicability.