ECP 2022 Abstract Book
Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 Results: Using top-40 differently expressed genes between SDHx -mutated and non- SDHx -mutated tumours, pathway enrich- ment analysis was performed. Based on KEGG database, four pathways enriched with upregulated genes and seven pathways enriched with downregulated genes were found (FDR ≤ 0.05). Using GO database, we revealed 75 pathways enriched by upreg- ulated genes (FDR ≤ 0.05) and no significant changes in path- ways enriched by downregulated genes. According to both data- bases, SDHx mutations are associated with expression changes in genes related to cell adhesion, extracellular matrix, PI3K-Akt, and VEGF signalling pathways. This work was performed using the equipment of EIMB RAS “Genome” centre (http://www. eimb.ru/ru1/ckp/ccu_genome_c.php ). Conclusion: Changes in biological pathways associated with SDHx mutations in VPGLs were firstly detected. We showed that well-known tumour-associated PI3K-Akt pathway can potentially be activated in SDHx -mutated tumours. Upregula- tion of genes involved in the VEGF signalling pathway in SDHx - mutated VPGLs is possibly associated with pseudohypoxic state that occurs as a result of succinate accumulation and HIF stabilization. Funding: This work was financially supported by a grant from Russian Science Foundation no.19-15-00419. PS-02-004 The significance of H3K9Me3 and H3K18Ac in salivary gland neoplasms E. Phattarataratip*, A. Lam-Ubol *Chulalongkorn University, Thailand Background & objectives: Histone modifications had been reported in different cancers with varying prognostic implica- tions. The objectives of this study were to examine the degree of acetylation and methylation of histone H3 in salivary gland neoplasms and their associations with prognostically-relevant pathologic characteristics. Methods: The expression of H3K18Ac and H3K9Me3 in 70 specimens of salivary gland neoplasms, consisting of 30 mucoepidermoid carcinoma (MEC), 20 adenoid cystic carcinoma (ACC) and 20 pleomorphic adenoma (PA), were investigated immunohistochemically. The immunohistochemical scoring was calculated in each case, based on both the staining intensity and the percentage of positive tumour cells. Results: H3K18Ac and H3K9Me3 were variably expressed in the majority of MEC, ACC and PA cases. Their expression appeared significantly correlated within this group of neoplasms. The increased H3K9Me3 in MEC was positively correlated with small nest invasion at tumour front and advanced grade pathologically. In addition, the solid subtype of ACC showed significant up-regulation of both H3K18Ac and H3K9Me3, compared with cribriform/tubular subtypes. Conclusion: Salivary gland neoplasms differentially acquire dis- tinct pattern of histone modification. Hyperacetylation and meth- ylation of histone H3 could be underpinning the prognostically worsen solid type of ACC, and the trimethylation of H3K9 may be involved in aggressive pathologic characteristics of MEC. Funding: This study was supported by Faculty Research Grant (DRF 64008), Faculty of Dentistry, Chulalongkorn University. PS-02-005 H3K9Ac expression in salivary gland tumours: correlation with histopathologic characteristics A. Lam-Ubol*, E. Phattarataratip *Srinakharinwirot University, Thailand Background & objectives: Acetylation of histone protein plays an important role in regulation of gene expression. Dysregulation of histone H3K9 acetylation was reported in various cancers and presented prognostic and therapeutic values. We aimed to examine H3K9Ac expression among common salivary gland tumours. Methods: Archived paraffin-embedded tissue of 30 mucoepider- moid carcinomas, 20 adenoid cystic carcinomas and 20 pleomor- phic adenomas were included in the study. H3K9Ac expression was evaluated by immunohistochemical staining. Expression of H3K9Ac were determined semi-quantitatively based on both stain- ing intensity and percentage of positive cells. The immunohisto- chemical scores were then evaluated according to various histo- pathologic features. Results: Mucoepidermoid carcinoma demonstrated significantly increased H3K9Ac expression compared with pleomorphic ade- noma. Moreover, the solid subtype of adenoid cystic carcinoma showed significantly higher H3K9Ac expression than the cribri- form/tubular subtypes. Conclusion: High levels of H3K9Ac appear to be associated with malignant salivary gland neoplasm and a more aggressive subtype of adenoid cystic carcinoma. PS-02-006 Predictive modeling for the diagnosis of oral and laryngeal premalignant and malignant lesions using expression of p53 and ki-67 J. Jeong*, K. Cho, H.J. Lee, Y.S. Lee, J.S. Song *Department of Pathology, Asan Medical Center, Republic of Korea Background & objectives: Oral and laryngeal epithelial lesions are diagnosed based on histologic criteria of WHO classification which may appear interobserver variability. Integrated diagnostic approach based on immunohistochemistry (IHC) is required that can help the interpretation of ambiguous histological findings of epithelial lesions. Methods: The oral cavity and larynx tissues of 118 cases from 108 patients were examined by IHC for p53 and Ki-67. Logistic regression analysis and decision tree algorithm were employed to develop the scoring system and predictive model for differentiat- ing the epithelial lesions. The comparison between TP53 mutation and expression patterns of p53 was conducted by Next-generation sequencing (NGS) and IHC. Results: The diffuse expression type (pattern HI) and null type (pattern LS) for p53, and pattern HI for Ki-67 were significantly associated with high-grade dysplasia (HGD) or squamous cell carcinoma (SqCC). With accuracy and the area under a receiver operating characteristic curve (AUC) of 85.3% and 85.4%, the scor- ing system based on p53 and Ki-67 classified epithelial lesions into two types: non-dysplasia or low-grade dysplasia, and HGD or SqCC. The decision tree model using p53 and Ki-67 classified epithelial lesions into non-dysplasia, dysplasia, and SqCC with accuracy and AUC of 64.7% and 80%. The patterns HI and LS for p53 were confirmed to be correlated with missense and nonsense/ frameshift mutations, respectively. Conclusion: The scoring system using p53 and Ki-67 may aid in the differentiation of epithelial lesions, especially when their morphologic features are ambiguous. PS-02-007 Comparison of PD-L1 immunohistochemical assays in head and neck carcinoma S70
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