Histologic features, nuclear grading, BAP1 and PD-L1 expression in malignant pleural mesothelioma

Diffuse pleural mesothelioma (DPM) is a rare tumor with an aggressive biological behavior. It is important to determine some prognostic factors, first the histologic subtype and further morphological parameters. Several immunohistochemical (IHC) stains, whose expressions have possible prognostic and therapeutic implications have been identified in DPM such as BAP1 and PD-L1. This study aims to evaluate the clinical significance and prognostic implications of such morphological features and IHC stains in 52 patients with a diagnosis of DPM, whose excision materials were examined in our institution between 2001 and 2022. The correlation between these parameters were also evaluated. Hematoxylin and eosin slides were re-evaluated and nuclear grading was applied for the epithelioid cases. BAP1 was interpreted in two compartments; in nucleus: loss/retained, in cytoplasm: positive / negative. 73-10 clone was used for PD-L1 IHC, cutoff levels were set as 1%, 50% and 80% and >1% staining was accepted as positive. Nuclear grading and necrosis were associated with survival; with shorter survival when necrosis was present and nuclear grade was III. BAP1 nuclear loss was seen in 69% of cases. There was no relation between cytoplasmic BAP1 staining and survival, yet cases with cytoplasmic staining were found to have >50% PD-L1 expression. 60% of the cases were PD-L1 positive (38% had 1-49% positivity, 10% had 50-79 positivity and 12% had >80% positivity). PD-L1 negative cases together with low expression group (1-49%) mostly had tubulopapillary pattern, which was classified under favorable criteria. One possible reason that higher PD-L1 positivity was observed compared to other studies was the higher sensitivity of 73-10 clone, but further studies with larger series are required to say so.