Mesothelin expression is a significant predictor for tumor aggression in patients with lung adenocarcinoma, suggest study findings published in Clinical Cancer Research.
Analysis of lung adenocarcinoma and healthy tissue samples from 1209 patients with stage I to III disease found that 69% of tumors expressed the cell-surface glycoprotein, whereas there was no expression in the normal tissue.
The 112 patients who had a high mesothelin expression (intensity plus distribution grade score of 5) had significantly lower 5-year overall survival than patients with low mesothelin expression (score 0–4) at 54% versus 67%, report Prasad Adusumilli and co-authors from the Memorial Sloan–Kettering Cancer Center in New York, USA.
High mesothelin expression was also significantly associated with poorer 5-year recurrence-free survival, at 48% versus 59%.
The hazard ratio (HR) for overall survival for patients with high versus low expression was 1.78, after adjusting for confounding factors such as age, gender, smoking, morphology, stage, and vascular invasion.
A high mesothelin expression score also significantly predicted overall survival after adjusting for EGFR and KRAS status, with an HR of 1.89, in a subset of 787 patients.
Of note, smoking was a significant predictor for mesothelin expression, with 97% of patients with high mesothelin expression former or current smokers. Patients with high mesothelin levels had a higher number of pack–years than those with low expression (mean 45 vs 36).
High expression of mesothelin was also associated with a papillary-predominant adenocarcinoma but other markers of adenocarcinoma aggression, such as lymphatic or vascular invasion, were not.
In vitro research confirmed that cells cultured to overexpress mesothelin had significantly higher levels of invasion and migration compared with control cells. And mice with tumors expressing high levels of mesothelin had a faster rate of disease progression and poorer survival than animals with tumors without mesothelin expression.
“As [mesothelin] overexpression provides a likely advantage to lung [adenocarcinoma] cells, this antigen is possibly important to the tumor’s growth and dissemination,” suggest Adusumilli et al.
“Thus, [mesothelin] expression provides a potential therapeutic target in patients with aggressive and therapy-resistant lung [adenocarcinoma] for future clinical trials.”
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