ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 OFP-09-015 Differential expansion of innate lymphoid cells and their role in oral squamous cell carcinoma S.A. Syed*, M.A. Qureshi, S. Khan, R. Kumar *Dow University of Health Sciences, Karachi, Pakistan Background & objectives: Oral cancers are the commonest reported cancers in Pakistani males and 2nd commonest in females. We investigated infiltration and potential role(s) of innate lymphoid cells (ILCs) in an accelerated murine model of oral carcinogenesis and in well-defined human cancers. Methods: We established an accelerated murine model of oral carcinogenesis and characterized tissue infiltration of ILCs in harvested cancer tissues using flowcytometry. We also investigated ILCs infiltration in well-defined human oral cancer tissues. Moreover, we inhibited ILCs using α-Th1 antibody to investigate potential role of ILCs in progression of oral cancers. Results: 84% of the mice treated with 9,10-dimethyl-1,2- benzanthracene (DMBA) carcinogenic regime developed moderately differentiated squamous cell carcinoma and showed differential expansion of ILCs in various cancers. Moreover, well defined human oral squamous cell carcinoma samples also exhibited increased infiltration of ILCs (along with increased expression of selected/ relevant cytokines). Tumour progression did not significantly differ upon inhibition of ILCs using α-Th1 antibody. However, ILCs expansion was different amongst the antibody treated and untreated groups. Conclusion: We present novel data on differential expansion of ILCs in oral cancers which demands further exploration to exploit these newly discovered cells to devise novel diagnostic, therapeutic and prognostic strategies to prevent/treat oral cancers. OFP-09-016 High-grade transformation in salivary gland tumours: a rare and under-recognized phenomenon N. Batra*, A. Patil, N. Mittal, S. Rane, K. Kante, M. Bal *Tata Memorial Hospital, India Background & objectives: High-grade transformation (HGT) in salivary gland tumours (SGT) is an extremely rare phenomenon associated with aggressive clinical course. Herein, we aimed to study the clinicopathological spectrum of SGT with HGT diag- nosed at our institute. Methods: Clinical data and pathologic material of all cases (2014- 2022) was reviewed and diagnosis confirmed as per the WHO 2017. HGT was defined by presence of unequivocal areas of high- grade carcinoma coexisting with conventional low-grade salivary gland carcinoma. Clinical and treatment details were recorded from the electronic medical records. Pathologic features of HGT and conventional areas were recorded and compared. Results: 18 cases were identified. The median age was 53 years; male-to-female ratio was 2:3. The sites included:submandibular (n=5), parotid (n=4), palate (n=4), tongue (n=2), and 1 case each in nasopharynx, nasal cavity, f loor of mouth, buccal mucosa, and maxilla. The histologic types included: adenoid cystic carcinoma (ACC, n=12), epithelial-myoepithelial car- cinoma (n=4), polymorphous adenocarcinoma (n=1), acinic cell carcinoma (n=1). HGT areas displayed high-grade cytol- ogy, necrosis, brisk mitoses, and higher Ki-67 in comparison to their low-grade counterparts. Poorly differentiated adeno- carcinoma was the most common HGT histology. Extra-paren- chymal spread, margin involvement, lymphovascular and peri- neural invasion were identified in 50%, 25%, 30%, and 50%, respectively. Conclusion: HGT of salivary neoplasms is a rare and frequently under-recognized occurrence that portends a poor prognosis. ACC is the most frequent underlying histology. Accurate diagnosis is essential as aggressive treatment is warranted. OFP-10 | Oral Free Paper Session Breast Pathology OFP-10-001 Mucoepidermoid carcinoma of the breast: multidimensional profiling reveals novel biomarkers and genetic drivers M. Ivanova*, K. Venetis, E. Sajjadi, S. Andaloro, C. Rossi, M. Lucioni, U. Malapelle, F. Pagni, M. Barberis, E. Guerini Rocco, G. Viale, N. Fusco *IEO, European Institute of Oncology, Italy Background & objectives: Breast mucoepidermoid carcinomas (MEC) are rare salivary gland-type triple-negative breast cancers (TNBC), often considered low-risk malignancies. Their biology is poorly understood, so they pose diagnostic and clinical challenges. We sought to characterize the molecular landscape of breast MECs. Methods: Thirteen breast MEC were histologically confirmed and subjected to tumour-infiltrating lymphocytes (TILs) profiling and PD-L1 (combined positive score, CPS), EGFR, and amphiregulin (AREG) immunohistochemistry. The MAML2 and EWSR1 rear- rangements (recurrent in salivary MECs) were investigated by fluorescent in situ hybridization. Eight cases with enough tissue material were subjected to next-generation sequencing (NGS) of 161 cancer-related genes. Results: Most cases were of low histological grade with Ki67<30% (n=10/13, 77%). TILs were found in 2 (17%) cases, while PD-L1 CPS ranged from 0 to 20 (median 12.5). All cases with available material showed EGFR overexpression and were AREG-positive (n=9/9, 100%). No MAML2 and/or EWSR1 rearrangements were detected. Pathogenic mutations in PIK3CA were highly recurrent (n=4/8; 50%), though only 1 (12.5%) case harboured a TP53 mutation. Additional somatic mutations affecting cancer-related genes found in MECs included CDK2, NF1/2, AKT1, SMARCB1, MYC, KRAS, CDK4, NOTCH1, and FGFR3/4. Taken together, complex patterns of genetic alterations were observed in PI3K/ AKT/mTOR and cell cycle regulation pathways. Conclusion: Here, we present the broadest collection of breast MECs comprehensively profiled for their molecular alterations. We demonstrate that these tumours lack the hallmark TP53 mutations often found in high-grade TNBC as well as MAML2 or EWSR1 rearrangements. The low TILs and PD-L1 levels suggest an immu- noediting deficiency and that MECs may unlikely respond to immunotherapy combination strategies. Finally, the EGFR-AREG axis activation, and genomic alterations in PI3K/AKT/mTOR and cell cycle regulation pathways warrant caution in considering MECs as low-grade TNBCs. OFP-10-002 Association of metastatic pattern in breast cancer with tumour type and patient specific factors: a nationwide autopsy study using artificial intelligence F. Kazemzadeh*, A. Snoek, Q. Voorham, N. Hugen, M.G.H. van Oijen, I. Nagtegaal *Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, The Netherlands, Cancer Center Amsterdam, Therapy Program, The Netherlands S39