ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 J. Shin*, S.J. Lee, J. Shin, P. Mattiolo, C. Luchini, S. Hong *Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea Background & objectives: Venous invasion (VI) is frequent in pancre- atic ductal adenocarcinoma (PDAC) than other cancers and it explains why PDAC is deadly. However, our understanding of VI in pancreatic undifferentiated carcinoma (UC) and undifferentiated carcinoma with osteoclast-like giant cells (UCOGC) is limited. Methods: Histopathologic characteristics of VI were evaluated with 44 (30 UCs and 14 UCOGCs) cases using triple CD31─D2- 40─desmin and e-cadherin immunostaining and clinicopathologic factors were compared with those of 471 PDACs. VI patterns were divided into three groups: conventional, intraepithelial neoplasia (IN)-like and destructive patterns. Results: VI was frequent in 3 cancers (PDAC, 64.3%, 303/471; UC, 70.0%, 21/30; UCOGC, 50.0%, 7/14; p=0.43). Mean VI foci number was higher in PDAC (3.3±3.6, p=0.004) than UC (2.0±2.1) and UCOGC (1.1±1.6). Mean number of IN-like (p=0.002) and destructive (p=0.033) patterns on H&E slides were higher in PDAC than UC and UCOGC. Triple CD31─D2- 40─desmin staining detected more foci of destructive pattern (p=0.018) than H&E, but no difference for detecting IN-like and conventional patterns. E-cadherin expression was lost in tumour cells invading stroma but was re-expressed within venous lumen of UCs and UCOGCs. Median survival time of UCOGC was significantly better compared to UC (UC, 5.52 months; UCOGC, 19.9 months; p<0.001). Conclusion: 1) VI was frequent both in UC and UCOGC like PDACs. 2) Triple CD31─D2-40─desmin staining could detect more VI foci of destructive pattern. 3) Sustained epithelial─mes enchymal─transition may not require for VI of UC and UCOGC. 4) VI alone could partly explain for different survival between UC and UCOGC patients, as all the measured indexes of VI, such as its overall prevalence, the mean number of foci, and the mean IN- like and destructive patterns, showed the lowest values in UCOGC. PS-13-011 Ex vivo patient-derived pancreatic cancer organoids to uncover individual therapeutic vulnerabilities and model acquired resistance S. Steiner*, A. Pliego, M. Haberecker, F. Arnold, D. Lenggenhager, C. Pauli *Institute of Pathology and Molecular Pathology, University Hos- pital Zurich, Switzerland Background & objectives: The acquisition of drug resistances con- tributes to poor survival of pancreatic cancer patients. Tumour organoid models not only bridges the gap between research and clinics but also offer a platform to study intrinsic drug sensitivities and predispositions to drug resistances. Methods: After establishing patient derived tumour organoids from a rare BRAF mutated pancreatic cancer patient and their genetic evalu- ation, we performed an ex vivo functional drug testing in order to identify specific drug vulnerabilities. The continuous exposure with trametinib lead to the formation of drug resistant organoid clones used for the subsequent RNA sequencing and expression analysis. Results: In an ex vivo functional drug testing, the BRAF organoids revealed a genotype specific sensitivity towards the MEK inhibitor trametinib when compared to other drugs. The induction of a drug resistance by continuous trametinib selection pressure further lead to the formation of resistant clones indicating a change in Wnt sig- nal regulation compared to their untreated counterparts. Sequencing analysis performed on the patient’s primary tumour specimen and the metastatic lesion revealed the acquisition of a GATA6 amplification, indicative for the underlying resistance mechanism, which resulted in the progression of the disease. Conclusion: We conclude that the use of patient derived tumour organoids represents a patient centered approach to investigate drug sensitivities and explore predispositions for drug resist- ances. The results generated by this approach assist in guiding and customizing therapy decision with the fundamental goal to improve the survival of pancreatic cancer patients. PS-14 | Poster Session Endocrine Pathology PS-14-001 Molecular pathological characteristics of benign thyroid nodules with poorly differentiated component M. Ueda*, K. Matsuda, H. Kurohama, Z. Mussazhanova, Y. Sailaubekova, H. Kondo, Y. Matsuoka, C. Otsubo, S. Sato, H. Yamashita, A. Kawakami, M. Nakashima *Department of Tumour and Diagnostic Pathology, Atomic Bomb Disease Institute, Nagasaki University, Japan Background & objectives: Thyroid follicular tumours (TFTs) showing nodule-in-nodule (NN) appearance with poorly differentiated component (PDc) but neither invasion nor metastasis are diagnosed as benign nodules regardless of high-grade histological features. This study aims at elucidating the malignant potential of PDc. Methods: This study analysed the profile of TP53 binding protein-1 (53BP1) expression by dual-colour immunofluorescence with Ki-67 and NRAS codon 61 mutations by droplet digital PCR in 16 cases of TFT showing NN with PDc compared to 30 adenomatous goiter (AG), 31 follicular adenoma (FA), 15 minimally invasive follicular carcinoma (MFC), and 11 widely invasive FC (WFC) cases. Results: The incidence of abnormal type 53BP1 expression in TFTs was significantly higher in the outer nodule (Out-N) (11.7%) and PDc (10.3%) in NN than AG (5.6%) and FA (6.5%) but not in MFC (14.2%) and WFC (17.1%). Furthermore, the frequency of double-positive cells with Ki-67 was significantly higher in PDc (0.36%) than in AG (0.03%), FA (0.12%), and Out-N (0.08%) but not in MFC (0.67%) and WFC (0.66%). The NRAS codon 61 mutation was the most frequently detected in both Out-N and PDc tumour areas (56.3%), and significantly higher than in AG (3.3%), FA (20.0%) but not in MFC (26.7%) and WFC (36.4%). Conclusion: This study demonstrated that the prevalence of abnormal type 53BP1 expression and NRAS mutations in PDc was comparable to FCs, suggesting a malignant potential at the molecular pathological level. Because co-localization of 53BP1 and Ki-67 can be an indicator of altered DNA damage response (DDR), the development of PDc may be associated with DDR impairments after harbouring an NRAS mutation. Thus, we should pay more attention to PDc as a precursor lesion associ- ated with poorly differentiated thyroid carcinoma. Funding: the Grant-in-Aid for Scientific Research from the Japa- nese Ministry of Education, Science, Sports and Culture (grant numbers 24590414, 26461951, 20K07424) PS-14-002 Histology of distant follicular cell–derived thyroid carcinomas metastases can be misleading to identify the primary tumour M.A. Rodríguez Villena*, N. Cadavid Fernández, A. Tenelanda Santillán, E. Moreno Moreno, I. González García, M.G. Rosas Hernández, H. Pian, I. Ruz Caracuel *H.U. Ramón y Cajal, Spain S137