Increased STAT expression in Reed–Sternberg cells as a potential positive prognostication biomarker in Hodgkin lymphoma

Classic Hodgkin lymphoma (cHL) prognostication primarily relies on clinical and radiological factors. Despite this, a subset of patients still progress. Immunohistochemistry (IHC) based biomarkers on diagnostic tissue have not been routinely used for prognostication. A multicentre retrospective analysis identified 62 patients with cHL. IHC on diagnostic tissues was used to stain Reed-Sternberg cells (RS) cells for STAT1, pSTAT3, p53 and tumour microenvironment for CD68 and PD-1. IHC stains were scored by anatomical pathologists blinded to patients and their outcomes and correlated with survival. Strong intensity of STAT1 and pSTAT3 staining correlated with improved overall survival (OS), with hazard ratios (HR) of 0.21 [95% confidence interval (CI) 0.06-0.76] and 0.22 (95% CI 0.06-0.84), respectively. Similarly, the median OS for weak versus strong STAT1 or pSTAT3 staining was 8.8 years versus not reached. Other IHC stains did not correlate with prognosis. In this cohort of cHL patients, downregulation of immunohistochemical STAT1 or pSTAT3 in RS cells is associated with inferior OS, suggesting STAT transcription within the pathognomonic RS cells may have tumour suppressor function and may be a potential biomarker for cHL prognosis.