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Breast Pathology 28A ANNUAL MEETING ABSTRACTS Breast Pathology Clincopathologic parameters n=68(%) Predominant MC 101 Overexpression of FoxO3a Is Associated with Lymph Node Squamous 31(45.5) Metastasis and Poor Disease-Free Survival in Triple-Negative Breast Spindle 15(22) Cancers Chondroid 9(13) Rehman Abdul, Yumin Chung, Hyein Ahn, Jongmin Sim, Min Sung Chung, Kiseok Jang. Osseous 4(6) Hanyang University College of Medicine, Seoul, Republic of Korea. Background: Triple negative breast cancer (TNBC) is the most aggressive type of breast Pseudoangiomatous 6(9) cancer, whichis a heterogeneous group and has no proven molecular target. FoxO3a, Mixed 2(3) a transcription factor, is involved in wide spectrum of biological processes, including HG sarcomatoid 1(1.5) cell cycle progression, proliferation, DNA damage repair, and apoptosis.Recently, DCIS with metaplastic features 14(52) accumulating evidences suggests that FoxO3a act as a tumor suppressorin variety Squamous 11(78.5) of human cancers. However,the previous studies usingTNBC cell lines have shown controversial results. The aim of this study was to investigate the clinicopathological Chondroid 2(14) significance and role of FoxO3a in the progression of TNBC. Rhabdoid 1(7.5) Design: Tissue microarrays consisting of 124 cases of TNBC were studied for FoxO3a None 13(48) expression by immunohistochemistry and interpreted by semi-quantitative scoring Grade system. The FoxO3a expression correlated with various clinicopathological parameters, 1 1(1.5) including patient’s survival. Furthermore, cultured TNBC cell lines (MDA-MB-231, MDA-MB-468, BT20) were assessed for FoxO3a expression by western blot. MDA- 2 3(4.5) MB-468 breast cancer cell line was transiently transfected with exogenous siRNA, 3 64(94) which wasspecific for FoxO3a. The effect of siRNA treatment on cell proliferation and Stage migration ability was analyzed by MTT assay and wound healing assay, respectively. I-II 46(68) Results: Overexpression of FoxO3a was correlated with adverse clinicopathological III-IV 22(32) features, such as lymph node metastasis (p=0.021, χ2-test) andperineural invasion (p=0.013, χ2-test). High FoxO3a expression is significantly correlated with poor Recurrence disease-free survival (p=0.015, log-rank test). The tumors with high FoxO3a expression Yes 12(17.5) had higher Ki-67 proliferation index (p=0.041, t-test). Among TNBC cell lines (MDA- No 56(82.5) MB-231, MDA-MA-468, and BT20), MDA-MA-468 had expression of FoxO3a by western blot analysis. There was no significant change in cell proliferation by siRNA- CD44+ CD24- ALDH1 SNAIL SLUG Vimentin E-cadherin mediated FoxO3a down-regulation in vitro. However, the inhibition of FoxO3arevealed DCIS, 8(73) 8(73) 4(29) 11(79) 6(43) 6(43) 6(43) to decrease cellular migration compared with negative controlin wound healing assay. n=14(%) Conclusions: FOXO3a may have a potential role of promoting invasion and proliferation of TNBC cells, and may be useful as prognostic biomarker and a Glandular component, 8(40) 8(40) 3(15) 11(55) 8(40) 11(55) 5(25) newpotential therapeutic targetin TNBC. n=20(%) Metaplastic 102 Role of Epithelial-to Mesenchymal Transition Markers in component, 20(100) 20(100) 13(65) 17(85) 14(70) 16(80) 17(85) Metaplastic Breast Cancer with Coexistent Ductal Carcinoma In-Situ n=20(%) Eman Abdulfatah, Rahman Chaudhry, Vishakha Pardeshi, Muhammad K Alsafadi, Conclusions: DCIS associated with MBC may show metaplastic features and express Sherif Shazly, Rouba Ali-Fehmi, Sudeshna Bandyopadhyay. WSU, Detroit, MI; Mayo, CSC and EMT markers. In our study, high SNAIL expression was associated with poor Rochester, MN. OS, suggesting its role as a potential prognostic marker. Background: Metaplastic breast carcinomas (MBC) are rare heterogeneous group of tumors that are part of the basal carcinoma spectrum, displaying a basal/myoepithelial and epithelial-to-mesenchymal (EMT) molecular makeup. However, the clinical 103 Histologic Characteristics of Breast Carcinomas with Genetic significance of EMT in MBC has not been fully investigated. In this study, we evaluated Variants of Uncertain Significance: the expression of EMT and cancer stem cell markers (CSC) in ductal carcinoma in-situ Ahmed Abdulrahman, Rebecca Heintzelman, Melanie Corbman, Fernando Garcia. (DCIS) and invasive component and correlated with phenotypic features and clinical Drexel University College of Medicine, Philadelphia, PA; Cancer Treatment Centers outcome. of America at Eastern Regional Medical Center, Philadelphia, PA. Design: Retrospective review of MBC (n=68) was conducted. Cinicopathologic Background: Starting in 2013, genetic testing laboratories incorporated additional genes parameters were analyzed (Table 1). Slides were reviewed for DCIS associated in the breast cancer molecular testing panel, resulting in detection of new mutations metaplastic features. IHC of CSC (CD44, CD24 and ALDH1) and EMT markers in approximately 40% of cases. When there is insufficient data to determine if the (vimentin, SNAIL, SLUG and loss of E-cadherin) expression was performed on whole variant causes increased cancer risk, these have been reported as variants of uncertain sections of a subset(n=20). Each marker was evaluated per established criteria and their significance (VUS). Histopathologic characteristics of VUS breast carcinomas (BCs) expression was correlated with overall survival (OS) using Kaplan-Meier anaylsis. have not been previously well-described. Our purpose is to describe common pathologic Results: All tumors were triple negative. Axillary lymph node metastasis was identified features in cases with similar VUS genes. in 22 cases (32%). 27 cases showed co-existent DCIS, of which 14 cases(52%) showed Design: In total, 19 VUS BCs were retrospectively identified and IRB approved from metaplastic features; the highest being squamous (11), followed by rhabdoid (2) and the Genetic Counselor’s office, consisting of eighteen female patients and one male chondroid (1). EMT and CSC markers showed variable levels of expression among patient. Ages ranged from 34 to 71 with a mean age of 53. Representative de-identified DCIS, glandular and metaplastic components (MC) (Table 2). Of all markers evaluated, H&E tumor sections were reviewed by three of the authors along with the reported CAP high SNAIL expression correlated with decreased OS (p=0.03). tumor characteristics and prognostic markers. In addition, the reported VUS germline mutations, peritumoral inflammation and peritumoral fibrosis were described. Results: Eight of the 19 cases were VUS with variants in the ATM gene. Three were in CHEK2, two in each of RAD51D, NBN, MUTYH, MLH1, BRCA2, CDKN2A, and one in each of MSH2, MSH6, PMS2, STK11, TP53, CDH1, BRCA1 and APC genes. The cases were grouped for histologic comparison into ATM (8) and non-ATM (11). ATM BC cases shared similar histologic characteristics when compared to variants in other genes. However, molecular subtyping assessed by immunohistochemistry was different. Histologic Characteristics ATM gene VUS (8/19) Non-ATM gene VUS (11/19) Peritumoral Inflammation Absent Present Peritumoral Fibrosis Prominent Variable Nuclear Grade 2 Nuclear Grade 3 Cytology Abundant eosinophilic Scant to moderate cytoplasm cytoplasm Luminal B, triple negative and Molecular Subtypes (in Luminal A, B and Her2 (A is 4 A (B is 6 cases, triple negative decreasing frequency) cases, B is 3 and Her2 is 1) is 3 and A is 2) Conclusions: 1. VUS BCs with ATM gene mutations shared similar histologic characteristics with lack of peritumoral inflammation and marked peritumoral fibrosis 2. VUS BCs with BRCA2 gene mutations shared high histologic grade with anaplasia 3. VUS BCs with MLH1 gene mutations were of pleomorphic lobular type 4. Further study is required to better assess the association of germline gene mutations with peritumoral inflammation and fibrosis ANNUAL MEETING ABSTRACTS 29A 104 Epithelial-Mesenchymal Transition and Cancer Stem Cells therapy (NAT) is a strong indicator of therapy benefit, and therefore, it is prognostic Interactions in Phyllodes Tumours: Clinical Relevance and Prognostic for favorable long-term outcome. To date, no biomarkers have been identified to Significance reliably predict pCR. Recent studies have shown that both tumor characteristics, such Syed Salahuddin Ahmed, Jabed Iqbal, Aye Aye Thike, Jeffry Chun Tatt Lim, Puay Hoon as grade and proliferation rate as well as host response, including immune infiltrate, Tan. Singapore General Hospital, Singapore, Singapore. play roles in the response to NAT. This study was undertaken to determine the role Background: Phyllodes tumours (PTs) are rare fibroepithelial neoplasms of the of TIL in predicting response to NAT with trastuzumab and anthracycline/taxane in breast and account for approximately 1% of all breast tumours. A constellation of patients with HER2+ BC. histological features such as stromal hypercellularity, stromal cell atypia, mitoses, Design: A single H&E stained slide was obtained from the diagnostic core biopsy from stromal overgrowth and tumour borders, further classify PTs as benign, borderline and 99 HER2+ patients who received NAT with trastuzumab and anthracycline/taxane. TIL malignant. Histological assessment may not always translate into tumor behaviour, were evaluated using the recommended consensus guideline from the International posing challenges in clinical management. TILs Working Group. Additional staining with anti-cytokeratin and anti-CD45, a pan- Epithelial–mesenchymal transition (EMT) is an important process during
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