ECP 2023 Abstracts

S171 Virchows Archiv (2023) 483 (Suppl 1):S1–S391 13 Results: A total of 25 patients diagnosed with invasive carcinoma of NST at the University of Szeged, were selected for this study. Patients with tumours showing no regression in tumour size following chemotherapy had numerous cytoplasmic RPB1 aggregated foci in their first biopsy samples, compared to those who responded to the therapy with either partial or complete regression of the tumour. After investigating the samples with known regression phenotypes, we tested the use of the RPB1 cytoplasmic phenotype screen in predicting therapy outcome by catego- rising samples into the three possible outcome groups in a blind experi- ment. Out of the 13 investigated samples we have managed to categorize 10 correctly. Conclusion: Given its predictive importance we find it urgent to report here that according to our results, the RPB1 complex has a tendency to aggregate in Epirubicin resistant tumour cells. The phenotype is easy to fol- low from biopsy samples immediately after diagnosing cancer. We propose that patients with cytoplasmic RPB1 foci in their biopsy samples should consider the high risk of an ineffective treatment with transcription blockers along with the time loss and chose surgery instead of neoadjuvant therapy. E-PS-02-073 Micropapillary mucinous breast carcinoma: a rare case with unu- sual features, and review of the literature L. Williams*, A. Vargiamidou *St George’s Hospital, London, United Kingdom Background & objectives: Micropapillary mucinous carcinoma remains an under-recognised variant, characterised by a high Ki-67 index, calcifi- cations, ER positivity, nodal metastasis and p63 expression. Controversy exists over whether these complex tumours should be classified as a pri- mary mucinous or a primary micropapillary neoplasm. Methods: A 59-year-old lady was presented to our university hospital with a right breast mass, revealed on imaging as a nodular density with pleo- morphic calcification. Biopsy showed a grade 2 invasive carcinoma (T3, P2, M1). The tumour displayed aberrant expression of p63, had strong ER and PR positivity, and a low Ki-67 index of 6-8%. Her2 was negative (1+). Results: Mastectomy revealed a 190mm micropapillary mucinous carci- noma, composed of morula-like aggregates with reverse polarity (confirmed on EMA staining) and frequent calcifications. 6/22 lymph nodes showed involvement, and background low-grade DCIS was present. Micropapillary mucinous breast carcinoma is a rare breast neoplasm (<1% of breast cancers), which sits between the more indolent inva- sive mucinous carcinoma and more aggressive invasive micropapillary carcinoma. Literature details both genetic alterations and a behaviour which lies between the two. Molecular studies have shown it to be genetically heterogenous in terms of both copy number alterations and genetic mutations. It has therefore been hypothesised that these inter- esting tumours can stem from either. Conclusion: This case of invasive micropapillary mucinous carcinoma is notable for both its unusual Ki-67 proliferation index, and its dimension of 190mm. This case is, to the best knowledge of the authors, one of the largest tumours of this type ever reported in literature. The recognition of this variant, particularly from pure mucinous car- cinoma, is of utmost importance, owing to their differing prognosis and impact on patient management. This case further highlights the heterogeneity of these rare tumours. E-PS-02-075 Claudin expression patterns in triple-negative breast cancer V. Zakharava*, A. Khorau, A. Portyanko *N.N.Alexandrov National Cancer Centre of Belarus, Belarus Background & objectives: The claudins expression is frequently dysregulated in the context of tumorigenesis, suggesting their role as biomarkers for diagnosis and prognosis. Objective was to study the morphological features of Claudin-3,-7 expression in patients with triple-negative breast cancer (TNBC). Methods: Biopsy material from patients with TNBC (n=91) was immunostained (IHC) with antibodies to Cytokeratin5/6, Cytokera- tin14, Claudin-3 (CLDN3), Claudin-7 (CLDN7), Androgen Receptor (AR), EGFR. Digital analysis of membrane/cytoplasmic expression was performed using QuPath-0.3.2 software with calculation of Allred score for CLDN3/CLDN7. Results: Three IHC subtypes of TNBC have been identified: Basal-like (BL, 78%), Luminal AR (LAR, 9%), mesenchymal with stem-like cells and low expression of CLDN3/CLDN7 (MSL, claudin-low – 2%) and mixed subtypes (11%). The levels and variability of CLDN3/CLDN7 expression for each IHC subtype were determined. The claudins expression had no significant differences between BL and LAR IHC subtypes, varying from 0 to 8 Allred score with a Me(CLDN3/7)=6/6 for BL subtype and Me(CLDN3/7)=6/5 for LAR subtype, respectively. At the same time, CLDN7 expression levels ≥7 were associated with a worse prognosis in breast-cancer-free survival in the BL subtype. Conclusion: The structure of TNBC was dominated by BL and LAR subtypes with single cases was regarded as MSL claudin-low subtype. The TNBC IHC subtypes criteria we have defined and available in the literature. IHC subtypes were characterized by variable levels of clau- dins expression with a worse prognosis of breast-cancer-free survival with CLDN7 overexpression. Funding: Governmental Grants 03.09 (2019-2022): To develop and implement a method of therapy for patients with triplet-negative breast cancer according to tumor subtype using chemotherapy including vincoalkoloids E-PS-02-076 ACTL6A: May be a prognostic and predictive indicator of high proliferative activity triple-negative breast cancer Y. Zhang*, Y. Zhou, Z. Wu, Q. Tao, F. Mengna, L. Yang, M. Shen, H. Bu, B. Wei, Z. Zhang *Sichuan University, China Background & objectives: Triple negative breast cancer (TNBC) with high proliferative is an aggressive subtype of breast cancer with poor tumour progression and prognosis. The purpose of this study was to explore clinicopathological features and biomarkers related to progno- sis of highly proliferative TNBCs. Methods: 192 cases of TNBCs in our institution from 2015 to 2021 were included. TNBCs were divided into high proliferative and low proliferative based on the Ki67 cut off of 50%. Using immunohisto- chemistry studies, AR, CD8, Forkhead box C1 (FOXC1), Double- cortin-like kinase protein 1 (DCLK1), BEN-domain containing 3 (BEND3), Actin-like 6A (ACTL6A), NK3 homeobox 1 (NKX3-1), SOX10 were evaluated in TNBCs. Results: There were 85 cases of low proliferative TNBCs and 107 cases of high proliferative TNBCs. Compared with low proliferative TNBCs, high proliferative TNBCs had few senior patients, more Grade 3 tumour, more AR negative tumour, more FOXC1 positive tumour, and more SOX10 positive tumour. Combined with univariate and mul- tivariate analysis, we found that tumour stage, ACTL6A high-expres- sion, CD8 negative/low-expression were related with poorer disease- free survival (DFS) and overall survival (OS) in TNBCs. However, in high proliferative TNBCs, ACTL6A high-expression was correlated with poor OS by univariate analysis and correlated with worse DFS by univariate and multivariate analysis. Patients with ACTL6A high- expression had more lymph node metastasis and larger tumour size. Conclusion: Patients with high proliferative TNBCs were more likely to express FOXC1 and SOX10, while patients with low proliferative TNBCs were more likely to express AR. ACTL6A, CD8 and tumour stage were associated with the prognosis of TNBC. It’s worth noting that ACTL6A high-expression was associated with poor prognosis of high proliferative TNBCs. More attention should be paid to the aggres- sive ACTL6A high-expression tumour. ACTL6A may be used as a cur- rently prognostic and predictive indicators of high proliferative TNBC.

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