Expression analysis of HMGB 1 in histological samples of malignant pleural mesothelioma

Aims High mobility group box 1 ( HMGB 1) is a chromatin structural protein, expressed ubiquitously in the nuclei of mammalian cells. When transported extracellularly, it acts as a tumour suppressor and oncogenic protein. In malignant pleural mesothelioma ( MPM ), high serum levels of HMGB 1 have been related to a poor prognosis. Conversely, the significance of HMGB 1 expression in MPM tissues is still unclear. Methods and results Biopsy samples from 170 patients with MPM were assessed by immunohistochemistry and reverse transcription–polymerase chain reaction ( RT – PCR ) to evaluate HMGB 1 protein and gene expression. The expression level of HMGB 1 protein was scored using a semiquantitative system that sums the intensity (0–3) and the percentage (from 0 to 4) of positively stained cells in nuclei, cytoplasm and in both. The final score was considered as high (>3) or low (<3) expression. Gene expression levels were calculated using the ΔΔC t method. High expression levels of HMGB 1 as total ( P = 0.0011) and cytoplasmic score ( P = 0.0462) were related to a worse disease‐specific survival ( DSS ) in the entire cohort and in the clinicopathological subgroups. No significant correlation was found between HMGB 1 gene expression and DSS . Conclusions These findings indicate that HMGB 1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB 1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.