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The distribution of intratumoral macrophages correlates with molecular phenotypes and impacts prognosis in colorectal carcinoma
Author(s) -
Kim Younghoon,
Wen Xianyu,
Bae Jeong M,
Kim Jung H,
Cho NamYun,
Kang Gyeong H
Publication year - 2018
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13674
Subject(s) - cd68 , cd163 , perineural invasion , microsatellite instability , stromal cell , immunohistochemistry , colorectal cancer , pathology , tumor infiltrating lymphocytes , macrophage , biology , medicine , cancer , cancer research , immunotherapy , biochemistry , allele , gene , in vitro , microsatellite
Aims The role of tumour‐associated macrophages ( TAM s) in colorectal cancer ( CRC ) remains elusive. In this study, we aimed to examine the correlation between TAM s, clinicopathological features, tumour‐infiltrating lymphocytes ( TIL s) and prognosis in CRC by the use of image analysis. Methods and results Immunohistochemical staining for CD 68 and CD 163 was performed as pan‐macrophage and M2‐macrophage markers, respectively. Each marker was analysed separately for intra‐epithelial and stromal area densities. All four macrophage densities showed a significant correlation with one another ( P = 0.001). Intra‐epithelial CD 68 + macrophage densities showed a correlation with pTNM stage ( P = 0.008), microsatellite instability ( MSI ) ( P < 0.001), CpG island methylator phenotype ( CIMP ) ( P < 0.001) and TIL densities ( P < 0.001). Intra‐epithelial CD 163 + macrophage densities were associated with perineural invasion, MSI , CIMP and TIL densities ( P < 0.001). Stromal CD 68 + and CD 163 + macrophage densities had a significant relationship with intra‐epithelial and stromal CD 3 + ( P = 0.001 and P < 0.001, respectively) and CD 8 + ( P < 0.001) T cells. High intra‐epithelial CD 68 + macrophage density was associated with worse overall survival ( HR = 1.386, 95% CI = 1.043–1.843, P = 0.025) and progression‐free survival ( HR = 1.522, 95% CI = 1.146–2.020, P = 0.004). Intra‐epithelial CD 68 + macrophage density was also an independent prognostic factor of the progression‐free survival ( HR = 1.447, 95% CI = 1.076–1.947, P = 0.015) of CRC patients regardless of pTNM stage, lymphatic, venous, and perineural invasions and TIL densities. Conclusion Our results indicate that the density of intratumoural macrophages is a useful prognostic indicator for further stratifying T cell populations in CRC .