ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 overall survival and disease-free survival, in addition to other path- ological parameters of worse prognosis. Therefore, we advocate for a widespread use of this system to help clinicians on patient risk assessment. Funding: Instituto Ramón y Cajal de Investigación Sanitaria - Intra- mural 2021 (projects grant 2021/0453). OFP-09-009 Apocrine differentiation in salivary duct carcinoma: immuno- histochemical evaluation for GATA3, p62 (Sequestosome1) and FABP7 in 106 cases K. Kusafuka*, K. Ueda, H. Inagaki, J. Itakura, Y. Otsuki, I. Ito, N. Kuroda, T. Daa, K. Suzuki, H. Iwai, K. Yamanegi, Y. Imamura, M. Hamada, M. Yasuda, S. Baba, E. Nakatani, M. Suzuki *Shizuoka General Hospital, Japan Ba ckg r o und & o b j e c t i ve s : Th e u p - r e g u l a t i o n o f p62(sequestosome1) and brain fatty acid binding protein(FABP7) was reported in apocrine carcinoma of the breast(ACB). Salivary duct carcinoma(SDC) is frequently seen as carcinomatous component of carcinoma ex pleomorphic adenoma(CXPA). We aim to elucidate their expressions in SDC. Methods: We selected SDC cases from a pathology file of 11 insti- tutions during 2000-2020, immunostained them for p62, FABP7 and GATA3, adding to androgen receptor(AR), and gross cystic disease fluid protein(GCDFP)-15. In the assessment for p62, nuclear signals were estimated as N type, whereas cytoplasmic signals were estimated as CY type. We examined with statistical analysis using R version 3.6.2 software. Results: One hundred six cases were selected as SDC, including 59 cases of CXPA (20 cases of intracapsular type, 8 cases of minimally invasive type and 31 cases of widely invasive type). Eighty one percent of SDC was positive for p62 (N type, 59%; CY type, 10%; N+CY type, 23%). Twenty-nine percent and 90% of SDC were positive for GATA3 and FABP7, respectively. Fifty-two percent and 45% of SDC were positive for AR and GCDFP-15, respectively. The expression status of p62 CY type or (-) was related to worse outcome, whereas the GATA3(+) cases were related to better outcome. Atypical pleomorphic adenoma expressed p62(N type only) in the atypical luminal cells. Conclusion: SDC should be called “apocrine carcinoma of the salivary glands”, due to the positivity for p62, FABP7 and GATA3, like ACB. Adding to GCDFP-15 and AR, the combinations of p62, FABP7 and GATA3 were considered to be new diagnostic markers for SDC. On the other hands, in the cases of CXPA, the luminal cells of PA may acquire the apocrine differentiation during the malignant transformation to SDC. OFP-09-010 The prognostic role of cortactin overexpression in oral squa- mous cell carcinoma of tongue: large cohort study B. Toközlü*, D. Sapkota, E.M. Vallenari, O. Schreurs, T. Soland *Gazi University, Turkey Background & objectives: Among oral cancer patients, those with squamous cell carcinoma of the oral (anterior 2/3rd) tongue are more likely to have higher mortality rates. Cortactin protein has been linked with progression and nodal involvement in the head and neck carcinoma. Methods: One hundred twenty-five HPV negative, formalin fixed paraffin embedded specimens were used to show cortacin expres- sion by constructing tissue microarrays using tissue cores of 2 mm diameter from both tumours invading front and the corresponding superficial/central areas. Followed by an analysis of tumour cell invasion in 3D-organotypic co-culture models after siRNA mediated silencing of CTTN gene. Results: Cortactin expression was higher at the invading core than at the corresponding central cores. High overall cortactin expression was positively associated with tumour size and distant metastases. High overall cortactin expression was associated with reduced 5-year overall survival. siRNA-mediated knockdown of cortactin resulted in reduced proliferative and invasive abilities of cell lines in 3D-organotypic co-culture models. Conclusion: We showed that the expression of cortactin was significantly higher at the invading cores than at the corresponding central cores. The results of current study also demonstrated that the overexpression of cortactin was associated with a significantly reduced overall survival. Increased expression of cortactin was similarly associated with tumour size and distant metastasis. These findings were further confirmed by analysing the invasive and proliferative abilities of cells in 3D-organotypics. Our findings suggest a prognostic value for cortactin in oral cancer. Funding: The author Burcu Toközlü was supported by a grant from TUBITAK 2021 during her stay in Oslo, and the project was sup- ported by North Norway Regional Health Authority (Helse Nord project no. SFP1276-16). OFP-09-011 Diagnostic utility of NR4A3 and NR4A2 immunohistochemistry in salivary gland pathology: a single-institution experience with 108 cases of acinic cell carcinoma N. Klubickova*, A. Skalova, O. Koshyk, E. Mosaieby *Bioptical Laboratory Ltd., Czech Republic Background & objectives: Acinic cell carcinoma (AciCC) is a common salivary gland malignancy, typically composed of neoplastic acinic cells with zymogen granules. The vast majority of cases are driven by a t(4;9)(q13;q31) leading to enhancer hijacking and upregulation of the NR4A3 gene. Methods: Seventy-one cases of classic low-grade AciCC, as well as 37 cases with high-grade transformation (HGT), were retrieved from institutional files and included in the analysis (n=108). Immunohistochemistry for DOG1, SOX10 and NR4A3 was performed in all cases; all NR4A3-negative and 10 NR4A3- positive cases were subsequently stained for NR4A2. FISH analysis of NR4A3 gene rearrangement was carried out in 1 case. Results: The patients’ age ranged from 17 to 86 years (mean=56). Patients with HGT were almost two decades older than patients with low-grade AciCC (mean=67 vs. mean=50). 67% of patients were female. One hundred cases were primary tumours, most com- monly occurring in the parotid gland, 6 cases represented recur- rences, and 2 lung/pleural metastases were sampled. Immunohis- tochemical staining for DOG1 and SOX10 was positive in 94% and 97% cases, respectively. NR4A3 was at least focally positive in 104/108 (96%) cases. NR4A3 rearrangement was confirmed by FISH in 1 analysed case. Out of the 4 NR4A3-negative cases, 2 dis- played strong nuclear immunopositivity with the NR4A2 antibody, while all 10 NR4A3-positive cases were negative. Conclusion: Our analysis confirms that majority of AciCC, including cases with HGT, are immunopositive for NR4A3, and suggests that NR4A3 immunohistochemistry is a powerful tool in the differential diagnosis of salivary gland tumours. However, its utility is limited in older and/or sub-optimally fixed samples which often display weaker and focal positivity. Our study also indicates that in minority of cases, AciCC might be negative for NR4A3 immunostaining because the pathogenic genetic event in these cases is rather the overexpression of NR4A2 . Funding: This study was supported by study grant SVV 260539 from the Ministry of Education, Czech Republic (NK). S37