Project Details

Description

Abstract:
Pleural mesothelioma (PM) and non-small cell lung cancer (NSCLC) are two highly lethal pleuro-pulmonary malignancies where ancillary analyses are needed for accurate diagnosis and (for NSCLC) treatment predictive testing, e.g. PD-L1. Diagnosis and analyses are traditionally based on histological material. However, a significant proportion of patients are diagnosed on cytological specimens, which are rapid and minimally invasive but less standardised regarding handling and fixative.
     In Paper I, PD-L1 expression was evaluated immunohistochemically in 61 paired biopsies and cell blocks with PM. The overall percentage agreement (OPA) between histology and cytology was 69%/84%, with a kappa of 0.36/0.08, at the ≥1%/>50% cutoffs. The cyto-histological correlation tended to be higher for epithelioid mesothelioma compared to non-epithelioid mesothelioma at the ≥1% cutoff.
     In Paper II, eight diagnostic immunohistochemical biomarkers were investigated in 59 paired biopsies and cell blocks with PM. The cyto-histological OPA for the epithelioid component was for calretinin 93%, CK5 98%, podoplanin 97%, WT1 90%, EMA 86%, desmin 100%, BAP1 91%, and MTAP 72%. Simultaneous loss or simultaneous preservation of both BAP1 and MTAP was observed in 40% and 11% of biopsies, while the corresponding figures were 54% and 8% for the paired cell blocks.
     In Paper III, PD-L1 expression was evaluated immunohistochemically in two cohorts of paired biopsies and cytological NSCLC specimens. Using a 3-tier scale, PD-L1 showed concordance in 40/47 (85%) and 66/97 (68%) cases in the two cohorts, with kappa values of 0.77 and 0.49, respectively. In 25 reviewed published studies comprising approximately 1,700 paired cases, the median cyto-histological concordance was 81-85% for a positive PD-L1 staining at the ≥1% cutoff and 89% at the ≥50% cutoff.
     In Paper IV, the impact of various clinicopathological and molecular factors on PD-L1 expression was investigated in two NSCLC cohorts of 1131 and 651 unpaired specimens (both 55% PD-L1 positive cases). Lower PD-L1 expression was seen in adenocarcinomas compared to squamous cell carcinomas, EGFR-mutated NSCLC compared to KRAS/EGFR wild-type and KRAS-mutated cases (highest expression), and in mucinous KRAS-mutated adenocarcinomas compared to non-mucinous.
     In Paper V, 24 pleural effusion cell blocks with lung adenocarcinomas were investigated for the effect of four common fixatives on the immunoreactivity of nine diagnostic markers. Differences in staining proportions were seen for TTF-1 clone 8G7G3/1 and EpCAM clone MOC-31, particularly with cases showing negativity in CytoLyt® (33.3% and 83.3% positive, respectively) and PreservCyt® (62.5% and 83.3%), while exhibiting positivity in CytoRich™ Red (76.5% and 94.1%) and formalin (both 95.8%). Weaker staining intensity was seen for all alcohol-based fixatives also for napsin A.
StatusFinished
Effective start/end date2020/01/012024/04/16

UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This project contributes towards the following SDG(s):

  • SDG 3 - Good Health and Well-being

UKÄ subject classification

  • Clinical Laboratory Medicine
  • Cancer and Oncology