Chi Peng Timothy Lai1, Joe Poh Sheng Yeong2,3, An Sen Tan1, Chong Hui Clara Ong2, Bernett Lee3, Jeffrey Chun Tatt Lim2,4, Aye Aye Thike2, Jabed Iqbal2,5, Rebecca Alexandra Dent6, Elaine Hsuen Lim6, Puay Hoon Tan7,8. 1. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore. 2. Division of Pathology, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore. 3. Singapore Immunology Network (SIgN), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore. 4. Institute of Molecular Cell Biology (IMCB), Agency of Science, Technology and Research (A*STAR), Singapore, Singapore. 5. Duke-NUS Medical School, Singapore, Singapore. 6. National Cancer Centre Singapore, Singapore, Singapore. 7. Division of Pathology, Singapore General Hospital, 20 College Road, Singapore, 169856, Singapore. tan.puay.hoon@singhealth.com.sg. 8. Duke-NUS Medical School, Singapore, Singapore. tan.puay.hoon@singhealth.com.sg.
Abstract
PURPOSE: We used multiplex immunofluorescence (mIF) to determine whether mitotic rate represents an independent prognostic marker in triple-negative breast cancer (TNBC). Secondary aims were to confirm the prognostic significance of immune cells in TNBC, and to investigate the relationship between immune cells and proliferating tumour cells. METHODS: A retrospective Asian cohort of 298 patients with TNBC diagnosed from 2003 to 2015 at the Singapore General Hospital was used in the present study. Formalin-fixed, paraffin-embedded breast cancer samples were analysed on tissue microarrays using mIF, which combined phospho-histone H3 (pHH3) expression with cytokeratin (CK) and leukocyte common antigen (CD45) expression to identify tumour and immune cells, respectively. RESULTS: Multivariate analysis showed that a high pHH3 index was associated with significantly improved overall survival (OS; p = 0.004), but this was not significantly associated with disease-free survival (DFS; p = 0.22). Similarly, multivariate analysis also revealed that a pHH3 positive count of > 1 cell per high-power field in the malignant epithelial compartment was an independent favourable prognostic marker for OS (p = 0.033) but not for DFS (p = 0.250). Furthermore, a high CD45 index was an independent favourable prognostic marker for DFS (p = 0.018), and there was a significant positive correlation between CD45 and pHH3 index (Spearman rank correlation coefficient, 0.250; p < 0.001). CONCLUSIONS: Mitotic rates as determined by pHH3 expression in epithelial cells are significantly associated with improved survival in TNBC. mIF analysis of pHH3 in combination with CK and CD45 could help clinicians in prognosticating patients with TNBC.
PURPOSE: We used multiplex immunofluorescence (mIF) to determine whether mitotic rate represents an independent prognostic marker in triple-negative breast cancer (TNBC). Secondary aims were to confirm the prognostic significance of immune cells in TNBC, and to investigate the relationship between immune cells and proliferating tumour cells. METHODS: A retrospective Asian cohort of 298 patients with TNBC diagnosed from 2003 to 2015 at the Singapore General Hospital was used in the present study. Formalin-fixed, paraffin-embedded breast cancer samples were analysed on tissue microarrays using mIF, which combined phospho-histone H3 (pHH3) expression with cytokeratin (CK) and leukocyte common antigen (CD45) expression to identify tumour and immune cells, respectively. RESULTS: Multivariate analysis showed that a high pHH3 index was associated with significantly improved overall survival (OS; p = 0.004), but this was not significantly associated with disease-free survival (DFS; p = 0.22). Similarly, multivariate analysis also revealed that a pHH3 positive count of > 1 cell per high-power field in the malignant epithelial compartment was an independent favourable prognostic marker for OS (p = 0.033) but not for DFS (p = 0.250). Furthermore, a high CD45 index was an independent favourable prognostic marker for DFS (p = 0.018), and there was a significant positive correlation between CD45 and pHH3 index (Spearman rank correlation coefficient, 0.250; p < 0.001). CONCLUSIONS: Mitotic rates as determined by pHH3 expression in epithelial cells are significantly associated with improved survival in TNBC. mIF analysis of pHH3 in combination with CK and CD45 could help clinicians in prognosticating patients with TNBC.
Entities:
Keywords:
Breast cancer; Immune; Prognosis; Proliferation; TNBC; pHH3
Authors: Harry Ho Man Ng; Ren Yuan Lee; Siting Goh; Isabel Shu Ying Tay; Xinru Lim; Bernett Lee; Valerie Chew; Huihua Li; Benedict Tan; Sherlly Lim; Jeffrey Chun Tatt Lim; Bijin Au; Josh Jie Hua Loh; Sahil Saraf; John Edward Connolly; Tracy Loh; Wei Qiang Leow; Joycelyn Jie Xin Lee; Han Chong Toh; Fabio Malavasi; Ser Yee Lee; Pierce Chow; Evan W Newell; Su Pin Choo; David Tai; Joe Yeong; Tony Kiat Hon Lim Journal: J Immunother Cancer Date: 2020-08 Impact factor: 13.751