Aye Aye Thike1,2, Xiaoyang Chen1,3, Valerie Cui Yun Koh1, Nur Diyana Binte Md Nasir1, Joe P S Yeong1,4, Boon Huat Bay3, Puay Hoon Tan1,2,3,5. 1. Department of Anatomical Pathology, Singapore General Hospital, Singapore. 2. Duke-NUS Medical School, Singapore. 3. Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. 4. Institute of Molecular and Cell Biology, A*STAR, Singapore. 5. Division of Pathology, Singapore General Hospital, Singapore.
Abstract
AIMS: Host immunity influences cancer progression and therapeutic response. We investigated the potential of tumour-infiltrating lymphocytes (TILs) around ductal carcinoma in situ (DCIS) in predicting recurrence and progression. METHODS AND RESULTS: CD4, CD8, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in DCIS from 198 patients was determined by immunohistochemistry. We correlated disease-free survival (DFS), clinicopathological parameters and biomarker expression with TIL density and CD4/CD8 ratio. High TIL density was associated with high nuclear grade (P < 0.001), DCIS PD-L1 expression (P = 0.008), TIL PD-L1 expression (P < 0.001), oestrogen (ER) negativity (P < 0.001), progesterone (PR) negativity (P < 0.001), human epidermal growth factor receptor 2 (HER2) positivity (P = 0.002) and triple negativity (P = 0.001). TIL PD-L1 expression was associated with triple-negative DCIS (P = 0.028). TIL density was associated with molecular subtypes (P < 0.001). High CD4+ T cell density was associated with high nuclear grade (P = 0.001), microinvasion (P = 0.037), ER negativity (P < 0.001), PR negativity (P = 0.001), HER2 positivity (P = 0.004), triple negativity (P = 0.023) and PD-L1 expression in TILs (P < 0.011). High CD4/CD8 ratio was associated with PD-L1 expression in DCIS (P = 0.035) and TILs (P < 0.001). DCIS with higher TIL density disclosed worse DFS (P = 0.012) and was affirmed with multivariate analysis [95% confidence interval (CI) = 1.109-2.554, hazard ratio (HR) = 1.683, P = 0.014]. Poorer DFS for ipsilateral invasive recurrence was found for DCIS with higher CD4+ T cell density (P = 0.006) or CD4/CD8 ratio (P = 0.02), confirmed by multivariate analysis for the former (95% CI = 1.369-10.196, HR = 3.736, P = 0.01) and latter (95% CI = 1.311-7.935, HR = 3.225, P = 0.011). CONCLUSION: DCIS with higher TIL density was associated with poorer prognostic parameters and predicted recurrence, while both CD4+ T cell density and CD4/CD8 ratio were associated with both recurrence and ipsilateral invasive recurrence.
AIMS: Host immunity influences cancer progression and therapeutic response. We investigated the potential of tumour-infiltrating lymphocytes (TILs) around ductal carcinoma in situ (DCIS) in predicting recurrence and progression. METHODS AND RESULTS:CD4, CD8, programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) expression in DCIS from 198 patients was determined by immunohistochemistry. We correlated disease-free survival (DFS), clinicopathological parameters and biomarker expression with TIL density and CD4/CD8 ratio. High TIL density was associated with high nuclear grade (P < 0.001), DCIS PD-L1 expression (P = 0.008), TIL PD-L1 expression (P < 0.001), oestrogen (ER) negativity (P < 0.001), progesterone (PR) negativity (P < 0.001), human epidermal growth factor receptor 2 (HER2) positivity (P = 0.002) and triple negativity (P = 0.001). TIL PD-L1 expression was associated with triple-negative DCIS (P = 0.028). TIL density was associated with molecular subtypes (P < 0.001). High CD4+ T cell density was associated with high nuclear grade (P = 0.001), microinvasion (P = 0.037), ER negativity (P < 0.001), PR negativity (P = 0.001), HER2 positivity (P = 0.004), triple negativity (P = 0.023) and PD-L1 expression in TILs (P < 0.011). High CD4/CD8 ratio was associated with PD-L1 expression in DCIS (P = 0.035) and TILs (P < 0.001). DCIS with higher TIL density disclosed worse DFS (P = 0.012) and was affirmed with multivariate analysis [95% confidence interval (CI) = 1.109-2.554, hazard ratio (HR) = 1.683, P = 0.014]. Poorer DFS for ipsilateral invasive recurrence was found for DCIS with higher CD4+ T cell density (P = 0.006) or CD4/CD8 ratio (P = 0.02), confirmed by multivariate analysis for the former (95% CI = 1.369-10.196, HR = 3.736, P = 0.01) and latter (95% CI = 1.311-7.935, HR = 3.225, P = 0.011). CONCLUSION: DCIS with higher TIL density was associated with poorer prognostic parameters and predicted recurrence, while both CD4+ T cell density and CD4/CD8 ratio were associated with both recurrence and ipsilateral invasive recurrence.
Authors: Anna K Casasent; Mathilde M Almekinders; Charlotta Mulder; Proteeti Bhattacharjee; Deborah Collyar; Alastair M Thompson; Jos Jonkers; Esther H Lips; Jacco van Rheenen; E Shelley Hwang; Serena Nik-Zainal; Nicholas E Navin; Jelle Wesseling Journal: Nat Rev Cancer Date: 2022-10-19 Impact factor: 69.800
Authors: Julia Solek; Jedrzej Chrzanowski; Adrianna Cieslak; Aleksandra Zielinska; Dominika Piasecka; Marcin Braun; Rafal Sadej; Hanna M Romanska Journal: Biomedicines Date: 2022-05-03