Expression analysis of High-mobility group box-1 (HMGB1) in histologic samples of malignant pleural mesothelioma

Abstract

Aims

High-mobility group box-1 (HMGB1) is a chromatin structural protein, ubiquitously expressed in the nuclei of mammalian cells. When transported extracellularly, it acts as tumor suppressor and oncogenic protein. In malignant pleural mesothelioma (MPM), high serum levels of High-mobility group box-1 (HMGB1) have been related to a poor prognosis. Conversely the significance of HMGB1 expression in malignant pleural mesothelioma (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 HMGB1 protein and gene expression. The expression level of HMGB1 protein was scored using a semi-quantitative system, that sums the intensity (0-3) and the percentage (from 0-4) 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 with ΔΔC_t method. High expression levels of HMGB1 as total (P = 0,0011) and cytoplasmic score (P = 0,0462), were related with a worse disease-specific survival (DSS) in the entire cohort and in the clinicopathologic subgroups. No significant correlation was found between HMGB1 gene expression and DSS.

Conclusions

These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, since it is expressed also in normal and reactive mesothelial cells, HMGB1 can not be considered a diagnostic biomarker, in histologic samples of mesothelioma.

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