ECP 2023 Abstracts

S5 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Methods: We screened 627 colorectal cancer (CRC) cases in the The- Cancer-Genome-Atlas (TCGA) datasets, and could establish SARIFA- status based on available diagnostic H&E whole-slide-images (https:// portal.gdc.cancer.gov) in 215 cases, of which 207 classified cases could be eventually included in final analysis. Consecutively, we performed differential gene expression analysis, gene set enrichment analysis as well as treatment prediction based on RNA-expression data. Results: 72 (33.5%) of all analysed cases were SARIFA-positive CRCs. Beyond again proving the prognostic value of SARIFA-status in this cohort, we could further show that survival differences seem not to be driven by alterations on a genomic level. However, SAR- IFA-positive CRCs were characterized by a distinct transcriptional profile. Even though SARIFA-positive CRCs were more likely to be of consensus-molecular-subtype (CMS) 4 and displayed a higher stromal-cell-infiltration-score (SIIS), SARIFA-positive CRCs were additionally again characterized by upregulation of genes associated with lipid metabolism (FABP4, CD36). Additionally, gene set enrich- ment analysis uncovered extracellular matrix organization as relevant SARIFA-dependent biological process. Lastly, RNA-based treatment response prediction revealed differential drug sensitivity in SARIFA- positive CRCs. Conclusion: Based on the TCGA, our study confirms the high prog- nostic value of H&E-based SARIFA-classification in CRC. SARIFA represents the H&E correlate of an aggressive tumour biology, partly showing an overlap with mesenchymal CMS4-subtype and SIIS score but furthermore being associated with lipid metabolism and possess- ing an ‘own’ transcriptional identity, which opens the window for new therapeutic approaches. Hence, SARIFA is an easy-to-implement bio- marker in diagnostic routine that could also be beneficial for more detailed patient stratification in prospective clinical trials. JNK is supported by the German Federal Ministry of Health (DEEP LIVER, ZMVI1-2520DAT111) and the Max-Eder-Programme of the German Cancer Aid (grant #70113864), the German Federal Minis- try of Education and Research (PEARL, 01KD2104C), and the Ger- man Academic Exchange Service (SECAI, 57616814). This research was funded/supported by the National Institute for Health and Care Research (NIHR, NIHR213331) Leeds Biomedical Research Centre. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. OFP-01-014 Tumour stroma ratio and tumour budding in colorectal adenocar- cinoma and its association with clinico-pathological parameters A.A. Khan*, S. Zaheer *Vardhman Mahavir Medical College, India Background & objectives: The pTNM classification in colorectal car- cinoma is based on anatomical evaluation and lacks predictive accu- racy. We aimed to study the association of tumour stroma ratio (TSR) and tumour budding (TB) with pTNM and histopathological grading in patients of colorectal adenocarcinoma. Methods: 40 patients, who underwent curative surgery for colorectal adenocarcinoma (CRC) were retrospectively included in this study. Hematoxylin and eosin stained sections of tumour were examined and TSR was calculated using a Java based open access image processing software (Image-J) and TB was calculated in hot spot region. These values were correlated with pTNM and histopathological grade. Results: Low TSR value i.e. < 0.5 was found in 26 patients (65%). We observed that low TSR (< 0.5) and high TB were significantly associated with poorly differentiated CRC (p < 0.0001 and p = 0.0001 respectively). A higher T and N stage and perineural invasion were significantly associated with low TSR ( p<0.005 and p<0.013, respec- tively ) . Overall, TSR showed higher sensitivity (100% versus 93.75%), specificity ( 50% versus 45%), positive predictive value (61.54% versus 57.69%), negative predictive value ( 100% versus 90%) and diagnostic accuracy (72.22% versus 66.67%) than TB in differentiating poorly dif- ferentiated colorectal carcinoma from moderately differentiated ones. Conclusion: The significance of tumour microenvironment is being increasingly recognized in various aspects including tumour progres- sion, prognosis and response to therapy. TSR is a relatively new, simple and promising histological biomarker which can be used as an inde- pendent prognostic marker along with TB in CRC for better clinical patients. The present study was limited to smaller number of patients and also needed more follow up of the patients for a comment on over- all survival were the limitations of this study. OFP-01-015 Early invasive (pT1) colorectal cancer: low PD-L1 expression in immune cells predicts the presence of nodal metastasis G. Trucco*, G.M. Benazzo, A.A. Ricci, L. Mangherini, E. Falco, A. Gambella, L. Bertero, P. Cassoni *Pathology Unit, Department of Medical Sciences, University of Turin, Italy Background & objectives: Nodal involvement in pT1 colorectal car- cinoma (CRC) is rarely present resulting in unnecessary surgeries. This study investigates the effectiveness of PD-L1 expression as a marker of lymph node metastasis for tailoring surgical treatment after endoscopic removal of pT1 CRC. Methods: Histopathological features of 19 metastatic and 62 non- metastatic surgically resected pT1 CRCs were assessed. Immunohisto- chemical expression of PD-L1 (clone 22C3) was evaluated using Tumour Proportion Score (TPS), Combined Positive Score (CPS), and Immune Cell Score (ICS). The correlation between PD-L1 expression and nodal metastasis, the optimal cut-off values, interobserver agreement and the potential impact on patients’ surgical management were determined. Results: PD-L1 expression in terms of CPS and ICS independently correlated with lymph node metastasis (PD-L1CPS: OR -2.5, 95%CI: -4.11 to -0.97, p=0.008 and PD-L1ICS: OR -1.85, 95%CI: -2.90 to -0.79, p=0.004) and <1.2 CPS and <1.3% ICS were identified as the optimal cut-off values to discriminate between metastatic and non- metastatic patients. In our cohort, the implementation of these cut-off values would have avoided a significant rate of unnecessary surgeries in pN0 patients (PD-L1CPS: 43.2; PD-L1ICS: 51.9%). Ultimately, PD-L1 evaluation showed good inter-pathologist concordance in absolute terms (PD-L1CPS Interclass correlation coefficient, ICC: 0.91; PD- L1ICS ICC: 0.793) and using the identified cut-off values (PD-L1CPS ICC: 0.848; PD-L1ICS ICC: 0.756). Conclusion: Our study shows that PD-L1 expression is an effective predictor of nodal status and could improve patient selection for sur- gery after endoscopic removal of pT1 CRCs. Good inter-pathologist concordance supports the potential reproducibility of PD-L1 immuno- histochemical evaluation in routine diagnostics. OFP-02 | Joint Oral Free Paper Session Gynaecological Pathology / Cytopathology OFP-02-001 CK17 and SOX2 immunohistochemistry in the distinction of HPV-independent p53 wild-type verruciform acanthotic vulvar intraepithelial neoplasia (vaVIN) from its mimickers and margin assessment E. Cook*, K.K. Van de Vijver, C. Parra-Herran *Brigham and Women’s Hospital, USA Background & objectives: vaVIN is a lesion with altered architecture, bland cytology and risk of recurrence and cancer progression, shown to be often CK17 and SOX2 positive. We document the performance