Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
Division of Pathology, Department of Medical Sciences, University of Turin, Turin, Italy.
Histopathology. 2018 May;72(6):1039-1050. doi: 10.1111/his.13470. Epub 2018 Feb 26.
High mobility group box 1 (HMGB1) 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 HMGB1 have been related to a poor prognosis. Conversely, the significance of HMGB1 expression in MPM tissues is still unclear.
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 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 method. High expression levels of HMGB1 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 HMGB1 gene expression and DSS.
These findings indicate that HMGB1 may be a useful prognostic biomarker in MPM when detected by immunohistochemistry. Conversely, as it is also expressed in normal and reactive mesothelial cells, HMGB1 cannot be considered a diagnostic biomarker in histological samples of mesothelioma.
高迁移率族蛋白 B1（HMGB1）是一种染色质结构蛋白，在哺乳动物细胞的核内广泛表达。当它被运送到细胞外时，它作为一种肿瘤抑制因子和致癌蛋白发挥作用。在恶性胸膜间皮瘤（MPM）中，HMGB1 的血清高水平与预后不良有关。相反，HMGB1 在 MPM 组织中的表达意义尚不清楚。
通过免疫组织化学和逆转录-聚合酶链反应（RT-PCR）评估 170 例 MPM 患者的活检样本，以评估 HMGB1 蛋白和基因表达。HMGB1 蛋白的表达水平采用半定量系统进行评分，该系统将细胞核、细胞质和两者中阳性染色细胞的强度（0-3）和百分比（从 0 到 4）相加。最终评分被认为是高（>3）或低（<3）表达。基因表达水平使用 ΔΔC 法计算。HMGB1 总评分（P=0.0011）和细胞质评分（P=0.0462）高表达与整个队列和临床病理亚组的疾病特异性生存（DSS）较差相关。HMGB1 基因表达与 DSS 之间没有显著相关性。
这些发现表明，HMGB1 可作为 MPM 的一种有用的预后生物标志物，通过免疫组织化学检测。相反，由于它也在正常和反应性间皮细胞中表达，HMGB1 不能作为间皮瘤组织学样本的诊断生物标志物。
