ECP 2023 Abstracts

S119 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Conclusion: The presence of multiple lung adenocarcinomas is an issue for staging. In this setting next Generation Sequencing could bring supplementary information and could be useful in the differentia- tion between intrapulmonary metastases and multiple primary tumours. A good correlation between histological examination and molecular analysis increases accuracy to assess the right staging for synchronous or metachronous lung adenocarcinomas. PS-20-002 Small bowel metastasis of lung cancers: clinico-pathological and molecular characterisation M.A. Bani*, L. El-Khoury, P. Dartigues, C. Smolenschi, I. Sourouille, B. Besse, S. Cotteret, J. Scoazec *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: Metastasis of lung cancer (MLC) is often detected at the time of diagnosis. Small bowel is the most frequent gastrointestinal metastatic site. The aim of this study is to explore the specificity of the involvement of small bowel in MLC. Methods: This retrospective analysis included 6 patients diagnosed with primary lung carcinoma with small bowel metastasis between 2003 and 2022 identified in our institution. The clinical features for each patient were obtained from the medical file. For each patient an immunohistochemical study and molecular testing using next genera- tion sequencing and RNA sequencing were performed. Results: The mean age at diagnosis was 66.2 years. 3 patients had synchronous metastasis and for the other 3 patients ileal metastasis was detected in the year following the diagnosis. Four cases were diagnosed with a primary lung adenocarcinoma, while two had a poorly differentiated adenocarcinoma. Only one case had an undif- ferentiated histology on metastasis with negative TTF1, CK7 and p40 and a loss of BRG1, revealing a SMARCA4 deficient undiffer- entiated tumour. There was no expression of NUT. KRAS mutations were detected in 3 cases, TP53 in 2 cases, BRAF in one case and SMARCA4 and CTNNB1 in one case. No fusion gene were detected by the RNA-sequencing panel used. Conclusion: To the best of our knowledge, there have been no studies on the clinicopathological and molecular characteristics of small bowel metastases from the lung. These metastases occur in advanced stage, are associated with unfavourable prognosis. Most of our patients had lung adenocarcinomas and one had a SMARCA4 deficient undifferentiated tumour. There were no peculiar molecu- lar profile since half of our cases harboured KRAS mutations. The characterisation of the immune microenvironment of these tumours is under investigation. PS-20-003 Anaplastic lymphoma kinase (ALK) status in non-small cell lung cancer (NSCLC), a prospective study/review of 2445 cases C. Girleanu*, J. Mc Fadden, S. McCarron, A. Dunne, M. Wright, G. Castriciano, S. Nicholson, A. Keogh, A.M. Baird, C. O’ Brien, S. Finn *Dept of Histopathology, LabMed Directorate, SJH, Ireland Background & objectives: The prevalence of anaplastic lymphoma kinase (ALK) fusion in non-small cell lung cancer (NSCLC) varies by detection method used. In our study we prospectively compared the detection of ALK rearrangements in NSCLC using Next-Generation Sequencing (NGS) and Immunohistochemistry (IHC). Methods: Analysis of ALK status was performed using NGS (Oncomine Focus panel) VENTANA anti-ALK (clone D5F3) Rabbit Monoclonal Primary Antibody, and IHC in 2475 cases of NSCLC diag- nosed in St James’s Hospital over the past 5 years. Discrepant cases were also tested using Fluorescence in situ hybridisation. Results were considered to be consensus positive/negative if reproduced across two methods. Results: 2445 cases of NSCLC were assessed with IHC and NGS. Of these, 216 cases had insufficient RNA for NGS, 32 had insufficient tissue for IHC and 67 cases were insufficient for both techniques, two cases had atypical laboratory findings and were not included in the comparative analysis. A total of 317 cases were excluded. Therefore, we analysed 2126 cases, 2108 cases showed concordance with both methods, 18 cases were discrepant between NGS and IHC. Consensus analysis using FISH demonstrated the NGS result to be consistent with consensus in 17/18 cases. Based on these numbers the accuracy of NGS is 99.9% and the accuracy of IHC 99.2%. Conclusion: Our study confirms that compared to IHC, NGS is a more accurate first line testing platform for the detection of consensus ALK fusion status. However access to IHC may be required to mitigate the higher tissue requirements of NGS and access to FISH may be benefi- cial to resolve atypical results. PS-20-004 Immunohistochemistry assessment of NTRK gene expressions in non-small cell lung cancer J.M. Gutiérrez Herrera*, M.A. Montero Fernández, G. Kokaraki, L. De Petris, R. Maia Falcão, J.Á. García García, R. Guijarro, S. Ekman, C. Ortíz Villalón *Karolinska University Hospital, Sweden Background & objectives: The NTRK gene-fusions has gained impor- tance in understanding tumour development and performance of TRKI inhibitors. The aim of this study was to assess the utility of pan-TRK immunohistochemistry for detecting NTRK gene rearrangements in non-small cell lung cancer. Methods: We conducted a retrospective analysis of 482 non-small cell lung cancer (NSCLC) cases from Karolinska University Hospital using pan-TRK IHC. Whole Exome Sequencing NGS was performed to con- firm the presence of NTRK fusions in pan-TRK IHC positive cases. We also used the IPA software to better understand the molecular pathways of lung cancer and suggest the best treatment option. Results: We detected TRK overexpression in 4.56% of the NSCLC cohort using pan-TRK IHC. The positive expression of TRK in NSCLC was correlated with histologic subtypes (adenocarcinomas, squamous cell carcinomas and large cell carcinomas), p < 0.0001; and grade of differentiation, p < 0.005. Overall were15 pan-TRK IHC positive cases, where 7 were confirmed to have NTRK fusions through NGS. NTRK2 and NTRK3 fusions were detected at a lower proportion compared to NTRK1 fusions. Other important somatic mutations were detected. Tumour burden in our cohort was high and there was not NTRK gene amplification but there was KRAS gene amplification in 1/15 samples. Conclusion: Pan-TRK IHC is a reliable and tissue-efficient method for identifying NTRK fusions in NSCLC. Further research is needed to understand the clinical significance of NTRK fusions in lung cancer and its role as potential targets for therapy. The IPA software is a useful tool for gaining a better understanding of molecular lung cancer pathways and suggesting the best treatment option. This study was funded in part by Bayer. PS-20-005 A review of the diagnosis and investigation of pulmonary amyloi- dosis and an evaluation of current local practice A. Hennessy*, C. Lightner, C. O’Brien, N. Mayer, L. Burke *Department of Pathology, Cork University Hospital, Cork, Ireland