Heterogeneity of cancer stem cell‐related marker expression is associated with three‐dimensional structures in malignant pleural effusion produced by lung adenocarcinoma

Abstract

AbstractIntroductionCancer stem cells have been described in lung adenocarcinoma‐associated malignant pleural effusion. They show clinically important features, including the ability to initiate new tumours and resistance to treatments. However, their correlation with the three‐dimensional tumour structures in the effusion is not well understood.MethodsCell blocks produced from lung adenocarcinoma patients' pleural effusion were examined for cancer stem cell‐related markers Nanog and CD133 using immunocytochemistry. The three‐dimensional cancer cell structures and CD133 expression patterns were visualized with tissue‐clearing technology. The expression patterns were correlated with tumour cell structures, genetic variants and clinical outcomes.ResultsThirty‐nine patients were analysed. Moderate‐to‐strong Nanog expression was detected in 27 cases (69%), while CD133 was expressed by more than 1% of cancer cells in 11 cases (28%). Nanog expression was more homogenous within individual specimens, while CD133 expression was detected in single tumour cells or cells within small clusters instead of larger structures in 8 of the 11 positive cases (73%). Although no statistically significant correlation between the markers and tumour genetic variants or patient survival was observed, we recorded seven cases with follow‐up specimens after cancer treatment, and four (57%) showed a change in stem cell‐related marker expression corresponding to treatment response.ConclusionsLung adenocarcinoma cells in the pleural effusion show variable expression of cancer stem cell‐related markers, some showing a correlation with the size of cell clusters. Their expression level is potentially correlated with cancer treatment effects.