Browsing by Author "Tan, Puay Hoon"

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    Multi-protein spatial signatures in ductal carcinoma in situ (DCIS) of breast
    (Springer Nature, 2021) Badve, Sunil S.; Cho, Sanghee; Gökmen-Polar, Yesim; Sui, Yunxia; Chadwick, Chrystal; McDonough, Elizabeth; Sood, Anup; Taylor, Marian; Zavodszky, Maria; Tan, Puay Hoon; Gerdes, Michael; Harris, Adrian L.; Ginty, Fiona; Pathology and Laboratory Medicine, School of Medicine
    Background: There is limited knowledge about DCIS cellular composition and relationship with breast cancer events (BCE). Methods: Immunofluorescence multiplexing (MxIF) was used to image and quantify 32 cellular biomarkers in FFPE DCIS tissue microarrays. Over 75,000 DCIS cells from 51 patients (median 9 years follow-up for non-BCE cases) were analysed for profiles predictive of BCE. K-means clustering was used to evaluate cellular co-expression of epithelial markers with ER and HER2. Results: Only ER, PR and HER2 significantly correlated with BCE. Cluster analysis identified 6 distinct cell groups with different levels of ER, Her2, cMET and SLC7A5. Clusters 1 and 3 were not significant. Clusters 2 and 4 (high ER/low HER2 and SLC7A5/mixed cMET) significantly correlated with low BCE risk (P = 0.001 and P = 0.034), while cluster 6 (high HER2/low ER, cMET and SLC7A5) correlated with increased risk (P = 0.018). Cluster 5 (similar to cluster 6, except high SLC7A5) trended towards significance (P = 0.072). A continuous expression score (Escore) based on these 4 clusters predicted likelihood of BCE (AUC = 0.79, log-rank test P = 5E-05; LOOCV AUC = 0.74, log-rank test P = 0.006). Conclusion: Multiplexed spatial analysis of limited tissue is a novel method for biomarker analysis and predicting BCEs. Further validation of Escore is needed in a larger cohort.
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    Phyllodes tumours of the breast: a consensus review
    (Wiley, 2016-01) Tan, Benjamin Y.; Acs, Geza; Apple, Sophia K.; Badve, Sunil S.; Bleiweiss, Ira J.; Brogi, Edi; Calvo, José P.; Dabbs, David J.; Ellis, Ian O.; Eusebi, Vincenzo; Farshid, Gelareh; Fox, Stephen B.; Ichihara, Shu; Lakhani, Sunil R.; Rakha, Emad A.; Reis-Filho, Jorge S.; Richardson, Andrea L.; Sahin, Aysegul; Schmitt, Fernando C.; Schnitt, Stuart J.; Siziopikou, Kalliopi P.; Soares, Fernando A.; Tse, Gary M.; Vincent-Salomon, Anne; Tan, Puay Hoon; Pathology and Laboratory Medicine, School of Medicine
    Phyllodes tumours constitute an uncommon but complex group of mammary fibroepithelial lesions. Accurate and reproducible grading of these tumours has long been challenging, owing to the need to assess multiple stratified histological parameters, which may be weighted differently by individual pathologists. Distinction of benign phyllodes tumours from cellular fibroadenomas is fraught with difficulty, due to overlapping microscopic features. Similarly, separation of the malignant phyllodes tumour from spindle cell metaplastic carcinoma and primary breast sarcoma can be problematic. Phyllodes tumours are treated by surgical excision. However, there is no consensus on the definition of an appropriate surgical margin to ensure completeness of excision and reduction of recurrence risk. Interpretive subjectivity, overlapping histological diagnostic criteria, suboptimal correlation between histological classification and clinical behaviour and the lack of robust molecular predictors of outcome make further investigation of the pathogenesis of these fascinating tumours a matter of active research. This review consolidates the current understanding of their pathobiology and clinical behaviour, and includes proposals for a rational approach to the classification and management of phyllodes tumours.
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    Tumor Infiltrating Lymphocytes in Multi-National Cohorts of Ductal Carcinoma In Situ (DCIS) of Breast
    (MDPI, 2022-08-13) Badve, Sunil S.; Cho, Sanghee; Lu, Xiaoyu; Cao, Sha; Ghose, Soumya; Thike, Aye Aye; Tan, Puay Hoon; Ocal, Idris Tolgay; Generali, Daniele; Zanconati, Fabrizio; Harris, Adrian L.; Ginty, Fiona; Gökmen-Polar, Yesim; Biostatistics, School of Public Health
    Tumor-infiltrating lymphocytes (TILs) are prognostic in invasive breast cancer. However, their prognostic significance in ductal carcinoma in situ (DCIS) has been controversial. To investigate the prognostic role of TILs in DCIS outcome, we used different scoring methods for TILs in multi-national cohorts from Asian and European women. Self-described race was genetically confirmed using QC Infinium array combined with radmixture software. Stromal TILs, touching TILs, circumferential TILs, and hotspots were quantified on H&E-stained slides and correlated with the development of second breast cancer events (BCE) and other clinico-pathological variables. In univariate survival analysis, age older than 50 years, hormone receptor positivity and the presence of circumferential TILs were weakly associated with the absence of BCE at the 5-year follow-up in all cohorts (p < 0.03; p < 0.02; and p < 0.02, respectively, adjusted p = 0.11). In the multivariable analysis, circumferential TILs were an independent predictor of a better outcome (Wald test p = 0.01), whereas younger age was associated with BCE. Asian patients were younger with larger, higher grade, HR negative DCIS lesions, and higher TIL variables. The spatial arrangement of TILs may serve as a better prognostic indicator in DCIS cases than stromal TILs alone and may be added in guidelines for TILs evaluation in DCIS.