ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 thickness of alveolar wall and smooth muscle shortening of air- way contributed in the subsequent enlargement of atelectatic areas. E-PS-21-020 The relevance of ACE2, TMPRSS2, and androgen receptor expression in male vulnerability to COVID-19 infection L. Di Sciascio*, F. Ambrosi, M. Riefolo, C. Ricci, L. Gabrielli, A. Degiovanni, G. Gaiba, P. Bertoglio, P. Solli, S. Damiani, A. D’Errico, M. Fiorentino *Pathology Unit, University of Bologna Medical Center, Italy Background & objectives: A sex-disparity in the outcome of patients with severe SARS-CoV-2 infection was observed during the pandem- ic’s first wave. We analyse these differences by evaluating the immu- nohistochemical expressions of ACE2, TMPRSS2 and Androgen Receptor(AR) within three groups: autoptic, asymptomatic and control. Methods: Patients have been divided as follows: - autoptic, died of SARS-CoV-2 infection, - asymptomatic, secondarily testing positive for SARS-CoV-2 - control, detected pre-pandemic. Each lung sample underwent histological and immunohistochemi- cal evaluation for AR, TMPRSS2, ERG, and ACE2. SARS-CoV-2 detection was performed through PCR and ISH. All clinical data were extracted from the patients’ medical records. Results: ACE2 immunohistochemical expression resulted strong and membranous in the autoptic group. In both asymptomatic and control groups, the overall expression of ACE2, TMPRSS2 and AR was low or absent regardless of the gender or the PCR positivity for SARS-CoV-2. Immunohistochemical staining of TMPRSS2 was negative in all patients of all three groups, but interestingly the only 3 positive cases with an high expression also showed high levels of immunoreactivity for ACE2, confirming its role in the cleavage of ACE2. AR expression in autoptic patients was difficult to assess, due to the postmortem lytic process. In addition to that, TMPRSS2:ERG gene fusion was not detected through immunohistochemical analy- sis in all samples. Conclusion: This study confirms the critical function of ACE2 in the viral pathogenicity of human tissues. A higher expression of ACE2 receptor, regardless of gender, was showed in the patients who died of SARS-CoV-2 complicated infection. Three autoptic patients showed also a stronger immunoreactivity for TMPRSS2 associated to a stronger expression of ACE2, confirming its role in the cleavage and activation of ACE2. E-PS-21-021 Prognostic impact of PD-L1 and PD-L2 expression in malignant pleural mesothelioma S. Yagci*, M. Tepeoğlu, E. Canpolat, P. Bayık, M. Kılıç, B.H. Özdemir *Başkent University Faculty of Medicine, Department of Pathol- ogy, Ankara, Turkey Background & objectives: Malignant pleural mesothelioma(MPM) is an aggressive malignant neoplasm associated with poor prognosis. Pro- grammed cell death ligand 1,2 (PD-L1,PD-L2) are important immune checkpoints that can inhibit T cell activation. Here we investigated the prognostic value of PD-L1 and PD-L2 in MPM. Methods: 91 patients who had a histological diagnosis of MPM made on pleural resection or biopsy at Baskent University between 2006 and 2022 were included in the study. Clinical and histopatho- logical data were collected from medical records. Tumour samples were analysed by immunohistochemistry for percentage of PD-L1 and PD-L2. The results were correlated with clinical parameters and outcome. Results: The mean age at diagnosis was 62±12.1 (range 35-87). The majority of patients were male (58, 63.7%). Most common histological type was epithelioid (77,84.6%), followed by sarcomatoid (10, 11%) and biphasic type (4, 4.4%). Among 91 patients, 36 (39.6%) had positive PD-L1 expression and 55 (60.4%) had negative. On the other hand, forty-seven (51,6%) patients were PD-L2 positive and 44 (48,4%) were PD-L2 negative. The positive rate of PD-L1 and PD-L2 in epithelioid MPM was 33,7% and 50.6%, while the rates were 71,4% and 85,7 respectively in sarcomatoid and biphasic MPM (p<0.05). The median survival time of PD-L1 negative patients were 2,2 times longer than PD-L1 positive ones. Conclusion: The positive rate of PD-L1 and PD-L2 were found to be sig- nificantly higher in sarcomatoid and biphasic types MPM, compared to epithelioid type. Also positive PD-L1 expression was found to be associated with lower median survival, while no significant association was found between PD-L2 and patient survival. Therefore, PD-L1 expression levels can be used to determine the prognosis of MPM patients, which may lead to treatment options for PD-L1. E-PS-21-022 Performance of AmoyDx HER2 mutation detection kit and AmoyDx Pan Lung Cancer PCR Panel for detection of com- mon HER2 and/or EGFR mutations M. Sheng*, H. Brown, S. Dearden *AstraZeneca, United Kingdom Background & objectives: HER2/ERBB2 mutations occur in 2-4% of NSCLC patients and clinical trials are assessing the efficacy of anti- HER2-antibody drug conjugate (ADC) therapeutics in NSCLC patients with HER2 mutations. We assessed the performance of two PCR assays for detection of HER2 mutations. Methods: Formalin-fixed paraffin-embedded (FFPE) cell blocks containing HER2 indel A775_G776insYVMA or single nucleotide variant V777L were generated at allele frequencies of 0%, 1%, 5% or 50%. Performance of AmoyDx HER2 Mutation Detection Kit was assessed for both mutations (n=3). AmoyDx Pan Lung Cancer PCR Panel was assessed for A775_ G776insYVMA in cell blocks (n=3) and EGFR exon19 deletions/ L858R in 4 NSCLC samples. Results: AmoyDx HER2 Mutation Detection Kit demonstrated a 100% pass rate at the recommended 10ng input DNA for HER2 A775_G776insYVMA and V777L at allele frequency ≥1%, with no false positives. The AmoyDx Pan Lung Cancer PCR Panel does not cover the V777L mutation but showed similar accuracy and sensitivity to the HER2 Mutation Detection Kit for the A775_ G776insYVMA indel, providing the correct amount of input DNA was used. The panel also correctly identified EGFR exon19 deletions and L858R mutations in the four clinical samples tested. Conclusion: Detection of rare mutations require sensitive and specific diagnostic assays. AmoyDx HER2 Mutation Detection Kit demonstrated robust performance in detecting representa- tive HER2 indel and single nucleotide variant mutations at low frequencies. The AmoyDx Pan Lung Cancer PCR assay showed similarly robust and sensitive detection of the common HER2 A775_G776insYVMA indel in addition to detecting clinically relevant EGFR mutations. Funding: This study is funded by AstraZeneca Pharmaceuticals. In March 2019, AstraZeneca entered into a global development and commercialization collaboration agreement with Daiichi Sankyo for trastuzumab deruxtecan (T-DXd; DS-8201). S334