ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 Background & objectives: Arylsulfatase B (ARSB) is a lysosomal enzyme with specific role in metabolism of chondroitin and dermatan sulfate. Few studies suggested it’s role in different carcinogenesis. The aim was to examine the association between ARSB and TP53 gene expressions in CRC. Methods: In this prospective study, 77 cases of CRCs were included. Gene expression of ARSB and TP53 was analysed after RNA isolation from fresh tissue samples. The expression level was determined using relative quantitation (RQ). RQ>1 was considered highly expressed whereas RQ<1 was used to identify low gene expressions for ARSB and TP53. Results: The statistical assessment showed a strong direct associa- tion between ARSB and TP53 gene expression levels (p<0.0001). Low expression was seen in 42 of the cases (54.55%) for both genes. In 15 out of the 77 cases (19.48%) both genes were highly expressed; these cases were mostly diagnosed in locally advanced stages (pT3/4), with high budding grade. The remaining cases (n=20; 25.97%) presented high ARSB and low TP53 expression. From the 62 cases with high ARSB gene expression level, 25 (40.32%) had mutation in one of the exons of the KRAS gene. These cases were mostly G2-adenocarcinomas with epithelial phenotype. Conclusion: All these findings suggest a possible prognostic role of ARSB in CRC and an association with TP53 gene. Further research might be necessary to understand the exact behaviour of this enzyme in such carcinomas. No similar data were reported in literature. Funding: This study was partially funded by the CNCS – UEFIS- CDI, project number 20 PCCF/2018. PS-15-013 The spectrum of gene fusions in primary epithelial ovarian tumours identified by panel RNA NGS approach I. Stružinská*, M. Flídrová, J. Galko, R. Jakša, K. Němejcová, M. Bártů, Q.H. Bui, J. Hojný, P. Dundr *Institute of Pathology, First Faculty of Medicine, Charles Univer- sity and General University Hospital in Prague, Czech Republic Background & objectives: Gene fusions represent somatic alterations involved in tumorigenesis of different cancers, and serve as diagnostic markers and/or therapeutic targets, although their incidence in ovarian tumours is unknown. Our aim was to characterize fusions in selected primary epithelial ovarian tumours. Methods: Sequencing libraries for paired-end capture RNA- Seq (147 genes; 373kbp; HyperCapture,Roche) were prepared using 300ng of total RNA isolated from FFPE tissues including mucinous borderline tumours (MBT;58), mucinous carcinomas (MC;36), high-grade serous carcinomas (HGSC;6), serous bor- derline tumours (SBT;23), and low-grade serous carcinomas (LGSC;53) and KAPA RNA HyperPrep kit (Roche), sequenced on NextSeq (Illumina), and biostatistically analysed using CLC Genomics Workbench (Qiagen). Results: A recurrent fusion TFG::ADGRG7 was found in 4/58 (7%) MBT, 2/36 (6%) MC, 1/23 (4%) SBT, and 1/53 (2%) LGSC. Inter- estingly, a known targetable recurrent fusion FGFR2::KIAA1217 was found only in the LGSC sample set (2/53; 4%). In total, eight different fusions were identified in 6/58 (10%) MBT, 2/36 (6%) MC, 1/23 (4%) SBT, 6/53 (11%) LGSC, and 1/6 (17%) HGSC. The fusion partners included known or potential therapeutic targets, such as BRAF, EGFR, FGFR2, NF1. Conclusion: The applied RNA-Seq approach revealed several known or novel fusions across different types of primary epithelial ovarian tumours. Extension of the analysed cohort and identifica- tion of fusions is ongoing and eventually will show fusion patterns, the role of gene fusions in targeted therapy and differential diag- nostics in rare ovarian primary tumours. Supported by Ministry of Health of the Czech Republic (NV19- 03-00007 and RVO64165, General University Hospital in Prague). PS-15-014 Development of a murine-model of oral carcinogenesis: a rapid tool for biomarker and anti-tumour drug discovery S.A. Syed*, M.A. Qureshi, S. Khan, R. Kumar, Y. Shafique, B.A. Khan, J. Safdar *Dow University of Health Sciences, Karachi, Pakistan Background & objectives: Oral squamous cell carcinoma (OSCC) is the commonest malignancy in Pakistani males and second only to breast cancer in females. We devised a novel accelerated murine model of oral carcinogenesis that can be exploited to identify molecules of diagnostic/therapeutic/prognostic significance. Methods: Total 40 healthy male, 6-8 weeks-old, 20-22 gram Naval Medical Research Institute(NMRI) outbred-strain mice were recruited. Of these, 25 were topically applied with 0.5% 9,10-dimethyl-1,2-benzanthracene in the lower lip for 20 weeks and 15 were used as controls. Harvested tissues were fixed and stained with hematoxylin and eosin. Additionally, expressions of CK 5/6, p53, and Ki-67 were investigated by immunohistochemistry. Results: All 25 mice (100%) who underwent accelerated carcino- genic regime developed tumours/lesions. The earliest lesion was developed on day 33 while the highest number of days taken for development of a lesion was 126. Average number of days taken by our mice to develop lesion was 84.56 days. Of 25 mice, 21 developed moderately differentiated squamous cell carcinoma and 1 showed dysplastic features with foci of invasion. Three mice were found dead despite developing lesions. CK 5/6 showed strong positivity (100%) and p53 and Ki-67 showed patchy (<30%) strong positivity in OSCC suggesting the similarity of our model to human OSCC. Controls did not show any morphological changes through- out the study. Conclusion: We present an accelerated, immunocompetent murine model of oral carcinogenesis using 9,10-dimethyl-1,2-benzanthar- acene in NMRI outbred strain mice. This model is close to human carcinogenesis that can be exploited as a tool to investigate and underpin molecular circuitry involved in oral carcinogenesis and to investigate various bio-molecules of diagnostic, therapeutic and prognostic significance. PS-15-015 The effect of mitochondrial energy metabolism modulators on cytotoxicity of cisplatin and pemetrexed in mesothelioma S. Sikiric*, A. Šepac, F. Sedlić, S. Seiwerth *University of Zagreb, School of Medicine, Croatia Background & objectives: The aim of this experiment was to inves- tigate whether pharmacological modification of mitochondrial energy metabolism together with high glucose concentrations could potentially be used for a more successful treatment of malignant mesothelioma. Methods: To access the resistance of mesothelioma cells to anti- neoplastic agents, cell proliferation was quantified in the Mero- 14 mesothelioma cell line after a 3 day treatment with different concentrations of antineoplastic agents pemetrexed and cisplatin (C/P) together with high glucose concentration alone or combined with mitochondrial energy metabolism modulators UK-5099, DNP, DCA. Cell proliferation was estimated using the MTT assay. Results: The addition of glucose alone did not significantly alter the cytotoxic effect of C/P and neither did UK-5099, DNP, nor DCA show an effect on cell proliferation when used at lower S144