ECP 2022 Abstract Book

Virchows Archiv (2022) 481 (Suppl 1):S1–S364 13 AAC. The statistically significant correlation between HMGA2 protein expression, loss of E-cadherin expression, and vimentin positivity support the role of HMGA2 in EMT. Funding: This study was supported by Eskişehir Osmangazi University Scientific Research Projects Coordination Unit Commission within the scope of project numbered 202111D02. OFP-03-010 Detection of perineural invasion in pancreatic adenocarcinoma using artificial intelligence S. Borsekofsky*, R. Hagege, D. Hershkovitz *Pathology Department of Tel Aviv Sourasky Medical Center, Israel Background & objectives: Perineural invasion (PNI) refers to invasion of cancerous cells around/in nerve. PNI is associated with a worse prognosis in pancreatic ductal adenocarcinoma (PDAC) with therapeutic target potential. We aimed to build an algorithm to identify PNI in PDAC more reliably/efficiently. Methods: Training the algorithm involved manual segmentation of nerve and tumour using 260 slide images from 6 scanned PDAC cases. Analytical validation used 168 additional images. Clinical validation had the algorithm applied to 59 cases of previously diag- nosed PDAC, presenting images of areas tumour and nerve were in closest proximity. A pathologist then determined presence or absence of PNI per case. Results: In the analytical validation, the algorithm showed sensi- tivity of 86%, 55% and specificity of 78% and 83% for the detec- tion of nerve and tumour, respectively. After incorporation of the tumour-nerve distance into the algorithm, PNI was identified in an additional 18 previously misclassified cases increasing the rate of detection from 52.5 to 81.4%. Interestingly, this required an aver- age of only 24 seconds per case. Conclusion: This algorithm was shown to be a very useful and time efficient tool to assist pathologists to more accurately and reliably identify PNI in PDAC. Of interest, training the algorithm to imitate pathologist thought processes (measuring the distance between tumour and nerve) allows development of a robust algo- rithm even based on a small cohort. OFP-03-011 Pre-invasive lesions of pancreatobiliary cancer: immunohisto- chemical signatures defining biological behaviour R. Vesce*, A. Yavas, L.J. Häberle, I. Esposito *Institute of Pathology, University Hospital Düsseldorf, Germany Background & objectives: We investigated the immunohisto- chemical expression profile of pre-invasive lesions of pancreatic ductal adenocarcinoma (PDAC) and cholangiocarcinoma (CCA) to detect staining patterns predicting risk of tumour-progression at early stages. Methods: We analysed 33 PanIN, 28 gastric (gIPMN) and 20 intes- tinal (iIPMN) IPMN, 18 BilIN and their associated invasive can- cers, when present (PDAC, n=23; CCA, n=6). We investigated the expression of markers associated with subtyping (MUC1, MUC2, MUC5AC, MUC6, CDX2), tumour biology (p16, p53, GATA6, Smad4, ki67), along with recently identified markers (TFF3, MUCL3). Results: PanINs, gIPMNs and BilINs displayed simi- lar phenotypes with MUC stains; however, MUCL3 was increased in gIPMNs(p=0.03) and BilINs(p=0.01) com- pared to PanINs. TFF3 was increased in BilINs, compared to PanINs(p=0.03). BilINs revealed focal MUC2(17%) and CDX2(38%) expressions. iIPMNs showed higher expression of MUC2,CDX2,TFF3, and higher Ki67-index than PanINs and gIPMNs(p<0.001). MUC1 was overexpressed in high-grade PanIN(p=0.02) and PDAC(p<0.001) compared to low-grade PanIN and in CCA compared to BilIN(p=0.001). MUC5AC was decreased in IPMNs and BilINs with associated invasive tumours compared to cases without invasive tumours(p=0.03 and p=0.03, respectively). MUC6 was decreased in PDAC compared to PanIN and gIPMN(p<0.001). Altered expression of GATA6,p53,p16 and SMAD4 was observed in high-grade lesions and/or cancers. Conclusion: iIPMNs display peculiar marker expression and higher proliferation rates compared to gIPMNs and PanINs, which are very similar to each other apart from the expression of MUCL3. BilINs and PanINs also show overall similar immunophenotypes. However, BilINs often present aberrant marker expression, differ- ent TFF3 and MUCL3 expression and higher proliferation rate. Altered expression of differentiation markers, such as MUC1, MUC5AC, MUC6 and GATA6 and of tumour-suppressors is asso- ciated with high-grade precursors and invasive cancers. Funding: Deutsche Forschungsgemeinschaft, project number ES 285/8-1 OFP-04 | Joint Oral Free Paper Session Soft Tissue and Bone Pathology / Infectious Diseases Pathology OFP-04-001 Whole-exome sequencing of chordoma with special emphasis on chromatin regulatory genes and recurrences S.R. Ullmann*, A. Roessner, J. Schreier, D. Schanze, C. Lohmann, M. Röpke, D. Jechorek, S. Franke *OvGU Magdeburg Department of Pathology, Germany Background & objectives: More insight into molecular genetics of chordoma is desired for defining new therapeutic strategies. We investigated 9 primary chordomas including one case with four recurrences. Special emphasis was put on chromatin regulatory genes and differences between recurrences and primary tumours. Methods: DNA was extracted from formalin- fixed, paraffin- embedded tissue samples of sacrococcygeal chordomas from patients between 39 and 78 years of age. After thorough qual- ity checking, the DNA was analysed by whole- exome sequencing with a NextSeq Illumina sequencer. In addition to histopathologi- cal tumour examination the expression of brachyury p53, Ki- 67,SMARCB and H3K36me3 was investigated by immunohisto- chemical techniques. Results: Consistent with our immunohistochemical findings and cur- rent literature our study revealed a pattern of typical molecular altera- tions including brachyury, p53, APC, BRCA, CDKN, and PI3K-sign- aling, in both recurrences and primary tumours. Interestingly our study found an increase in quantity of mutations over time in the recurrences, most of all in chromatin regulatory genes but also in rarer Genes like LYST and HYDIN. In all cases histone modifiers (KMT, KDM) and CRC-family members especially coding for the SWI/SNF- and ISWI- complexes (SMARC, ARID, PBRM) had a high number and variety of mutations. The number of SNVs and InDels did not show significant differ- ences between the primary and recurrent tumours. Conclusion: The increasing number of alterations in chromatin- regulatory genes in recurrences compared to primary tumours could point to a possible importance of these alterations in recur- rence development and be the basis for new targeted therapy strat- egies of chordoma. The progress in tumour mutation burden as well as copy number variations in recurrences were more limited compared to the genetic evolution of carcinomas with long time S14