ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 and p= 0.015, respectively). No significant association was found about RAS, TERT, PIK3 and RET alterations and persistent/recur- rent disease, PD-L1 and AXL expression. Conclusion: This data suggests that BRAF mutation and AXL (hyper)expression are correlated with increased expression of PD-L1 and CD8 in PTC patients with persistent disease with respect to those without persistent/recurrent disease after initial treatments. Accordingly, they should be considered as potential biomarkers of aggressive behaviour of PTC also suggesting other possible therapeutical targets. OFP-09-005 Medullary thyroid carcinoma: conventional and emerging prognostic factors M. A. Bani*, M. Faron, C. Kanaan, P. Khneisser, L. Lacroix, L. Lamartina, J. Hadoux, D. Hartl, V. Suciu, X. Sastre-Garau, E. Baudin, J. Scoazec, A. Al Ghuzlan *Department of Medical Biology and Pathology, Morphological pathology laboratory, Gustave Roussy Cancer Campus, Villejuif, France / Paris-Saclay university, Gustave Roussy Cancer Centre, Inserm US23, CNRS UMS3655, AMMICa, Villejuif, France Background & objectives: Prognosis of patients with medullary thyroid carcinoma (MTC) remains difficult to establish. The objec- tive of our study was to evaluate the prognostic value of the patho- molecular characteristics in MTC. Methods: Tumour tissues from primary MTC patients diagnosed at Gustave Roussy between 2003 and 2020 were reviewed to assess conventional prognostic factors and immunophenotype. Mutational status of RET was determined using New Generation Sequencing. Outcomes included overall survival (OS), biological (B-DFS) and morphological disease free survival (M-DFS). Univariate and mul- tivariate statistical studies were conducted. Results: 207 patients were included: 56% were females and the median age was 54 years. In the univariate study for OS: age (>50 years), size (>4cm), extrathyroidal extension, positive surgical margins, absence of encapsulation (AE), necrosis, high mitotic index (MI) (≥5 mitosis/2mm2), lymphovascular invasion, atypi- cal mitosis were significantly associated with poor outcome. In the multivariate study, only AE(p=0.034), necrosis(p=0.001) and MI(p<0.001) remained statistically significant. Using the IMTCGS grading system, high grade tumours (MI≥5 and/or Ki67≥5 and/or necrosis) were associated to a decreased OS, B-DFS and M-DFS. Somatic RET_M918T mutation was found in 31/127(37%). There were no prognostic significant difference between high grade (15/50) and low grade (16/77) RET mutated MTC. Conclusion: In patients with MTC, AE, necrosis and high MI were associated with poor OS, thus validating the prognostic value of IMTCGS in an independent cohort. Ten of the high grade and seven of the low grade RET_M918T mutated cases experienced relapse, suggesting that this biological trait may represent an independent biological prognostic factor from IMTCGS. Analysis of a larger panel is necessary to confirm these data. OFP-09-006 Differential expression profiles of immunoregulatory genes in poorly differentiated and anaplastic thyroid carcinomas pro- gressive from papillary carcinoma G. Orlando*, J. Metovic, F. Maletta, C. Tampieri, F. Napoli, V. Zambelli, M. Volante, M. Papotti *University of Turin, Italy Background & objectives: Few data are available on the immu- noregulatory mechanisms of thyroid cancer, with special reference to aggressive forms. We aimed at identifying profiles of expression of immune-related genes in anaplastic (AC) and poorly-differenti- ated (PDC) carcinomas with associated papillary carcinoma (PC) components. Methods: Expression levels of over 700 genes involved in immune to tumour response mechanisms were investigated by using the nCounter® PanCancer Immune Profiling Panel in 9 PDC and 12 AC, all having a PC associated component. Moreover, in the 12 AC cases the matched PC component was analysed in parallel. Results: Over 200 genes were differentially expressed in PDC as compared to AC samples, affecting all main pathways covered by the panel. All pathways were down-regulated in PDC. Pair- wise analysis of AC and matched PC components showed a stable pattern of expression for most genes, with a few showing a high statistically significant differential expression (p<0.001 in t test analysis). Among those, 5 (MAP3K1, PRKCD, CYFIP2, BLNK and EPCAM) were down- and 6 (RIPK2, ITGB1, CCL3L1, ITGA5, PLAUR and TICAM2) were up-regulated in AC. Interestingly, for 9 of these 11 genes the pattern of deregulation between PC and AC components was consistent in all samples. Conclusion: PDC and AC possess specific and different expression profiles of immunoregulatory genes even in the presence of a similar histological pattern of progression. Unexpectedly, progression of PC to AC is not associated with a wide deregulation of immunoregulatory mechanisms. However, a subset of genes is consistently impaired during AC progression, whose role as biomarkers and functional mechanisms need to be assessed and validated in future studies. Funding: This work was supported by the Associazione Italiana per la Ricerca sul Cancro (Milan, Grant IG 20110 to M.P.). OFP-09-008 High-grade medullary thyroid carcinoma, morphological fea- tures and prognostic value of the international grading system C. Ariño-Palao*, R. Meléndez Gispert, H. Pian-Arias, T. Caniego- Casas, J. Molina Cerrillo, T. Alonso Gordoa, I. Ruz Caracuel *Ramón y Cajal University Hospital, Spain Background & objectives: Medullary thyroid carcinoma (MTC) is a rare malignant tumour without a widely accepted grading scheme. In 2021, a multicentric study developed the International Medul- lary Thyroid Carcinoma Grading System. We seek to employ this system and analyse its prognostic value. Methods: We reviewed slides from a single-centre cohort of 28 MTC since 2002. Tumours were assigned high-grade based on the presence of at least one of three parameters: mitotic index ≥5 mitosis/2mm2, Ki67 proliferative index ≥5%, and tumour necrosis. We compiled additional pathological features and clinical informa- tion to perform a survival analysis. Results: We identified 7 high-grade carcinomas (25%) and 21 low-grade carcinomas (75%). Two high-grade carcinomas showed all three parameters, whereas one presented both Ki67 prolifera- tive index and tumour necrosis. Two expressed only Ki67 prolif- erative index ≥5% and the remaining two had tumour necrosis. High-grade carcinomas frequently showed an infiltrative pattern, spindle cell morphology, lymphovascular invasion, lymph node metastasis at diagnosis, AJCC stage III or IV, extrathyroidal extension, and affected surgical margins. Statistical analysis demonstrated decreased overall survival (median 41.57 months vs 64.80 months; LR= 17.412; p<0.001) and decreased disease- free survival (median 6.57 months vs 46.87 months; LR= 10.276; p=0.001) in high-grade carcinomas. Conclusion: We confirm the prognostic value of the International Medullary Thyroid Carcinoma Grading System in an independent cohort. High-grade carcinomas associated significant decreased S36