HSP90 expression is associated with outcome in pulmonary carcinoid tumor patients

BACKGROUND: Pulmonary carcinoids (PCs) are rare tumors that account for <2% of all lung cancer cases. Patients who undergo resection for PC tumors generally have a favorable prognosis, but there is a risk for late recurrence and distant metastasis. The objective of this study was to identify biomarkers for PC tumors using RNA sequencing and immunohistochemistry. METHODS: A total of 128 formalin-fixed, paraffin-embedded PC tumor samples from patients surgically treated at Helsinki University Hospital between 1990 and 2013 were analyzed in the study. RNA sequencing was first used to detect genes with higher expression in specific histological subtypes and metastatic and nonmetastatic tumors than in adjacent lung tissue. The diagnostic potential of the biomarkers was assessed using immunohistochemistry. RESULTS: Through gene expression analysis, HSP90AB1 expression was found to be significantly elevated in metastatic PC tumors (P<0.0001). The paralog of the gene, HSP90AA1, was also overexpressed, but the finding was not statistically significant. Through immunohistochemical analysis, HSP90 protein expression was found to be associated with shorter disease-specific survival (DSS) (P=0.009) and increased risk of disease-specific death [hazard ratio (HR) 6.4, 95% confidence interval (CI): 1.3–31.8]. CONCLUSIONS: This study confirms that HSP90 has a prognostic role in PC tumors and that inhibition of HSP90 may possess therapeutic potential in the management of PC tumor patients in the future.