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28.11.2016 | Urologic Oncology | Ausgabe 5/2017

Annals of Surgical Oncology 5/2017

Tumor Infiltrating Mast Cells (TIMs) Confers a Marked Survival Advantage in Nonmetastatic Clear-Cell Renal Cell Carcinoma

Zeitschrift:
Annals of Surgical Oncology > Ausgabe 5/2017
Autoren:
MD Hangcheng Fu, MD Yu Zhu, MD Yiwei Wang, MD Zheng Liu, MD Junyu Zhang, MD Zewei Wang, MD Huyang Xie, MD Bo Dai, MD, PhD Jiejie Xu, MD Dingwei Ye
Wichtige Hinweise
Hangcheng Fu, Yu Zhu and Yiwei Wang have contributed equally to this work.

Abstract

Purpose

The role played by the innate immune system in determining the clinical outcome of clear-cell renal cell carcinoma (ccRCC) was still blurred. This study was designed to investigate the prognostic significance of tumor infiltrating mast cells (TIMs) in ccRCC.

Methods

The study retrospectively enrolled a training set (474 patients) and a validation set (188 patients) with nonmetastasis (pT1-4N0M0) ccRCC from two institutional medical centers of China. TIMs was evaluated by immunohistochemical staining of tryptase and its association with clinicopathologic features and prognosis were evaluated.

Results

In ccRCC tissues, TIMs ranged from 0 to 103 cells/mm2 and 0 to 113 cells/mm2 in the training set and validation set, respectively. TIMs was negatively correlated with tumor size (P < 0.001 and P < 0.001, respectively), pathological T stage (P = 0.005 and P = 0.007, respectively) and Fuhrman grade (P < 0.001 and P < 0.001, respectively). Patients with abundant TIMs infiltration showed significantly longer cancer-specific survival in the training cohort and the validation cohort (P < 0.001 and P < 0.001). Patients with abundant mast cell infiltration showed significantly longer overall survival in the TCGA cohort (P < 0.001). Moreover, multivariate analysis identified TIMs as an independent prognostic factor for cancer-specific survival (CSS) and relapse-free survival (RFS). Also, TIMs was significantly correlated with CSS and RFS of the mediate and high-risk patients in the training cohort and the validation cohort.

Conclusions

TIMs density is a powerful independent prognostic factor for CSS and RFS in patients with nonmetastasis (pT1-4N0M0) ccRCC.

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Zusatzmaterial
Supplementary material 1 (DOCX 17 kb)
10434_2016_5702_MOESM1_ESM.docx
Supplementary material 2 (DOCX 17 kb)
10434_2016_5702_MOESM2_ESM.docx
Supplementary material 3 (DOCX 16 kb)
10434_2016_5702_MOESM3_ESM.docx
Figure S1 Consort Diagram outlining patient selection criteria and exclusion criteria. In the figure, n1 and n2 represent the training cohort and validation cohort respectively (TIFF 7448 kb)
10434_2016_5702_MOESM4_ESM.tif
Figure S2 Tryptase expression in clear-cell renal cell carcinoma (ccRCC) tissues. (A) Peritumoral mast cells (MCs) infiltration with 200 × magnification. (B) Peritumoral mast cells (MCs) infiltration with 400 × magnification. (C) Intratumoral mast cells (MCs) sparse infiltration with 200 × magnification. (D) Intratumoral mast cells (MCs) sparse infiltration with 400 × magnification. (E) Intratumoral mast cells (MCs) abundant infiltration with 200 × magnification. (F) Intratumoral mast cells (MCs) abundant infiltration with 400 × magnification. (TIFF 16508 kb)
10434_2016_5702_MOESM5_ESM.tif
Figure S3 Raw data of mast cell density and mast cell distribution density in peritumoral tissue, intratumoral tissue of training set and validation set. (A). Mast cells density against survival in months of peritumoral tissue of training set. (B) Mast cells distribution density of peritumoral tissue of training set. (C) Mast cells density against survival in months of intratumoral tissue of training set. (D) Mast cells distribution density of intratumoral tissue of training set. (E) Mast cells density against survival in months of intratumoral tissue of validation set. (F) Mast cells distribution density of intratumoral tissue of validation set. (TIFF 19622 kb)
10434_2016_5702_MOESM6_ESM.tif
Figure S4 Nomogram and calibration plot for prediction of clinical outcomes in patients with clear-cell renal cell carcinoma (ccRCC). (A) Cancer-specific survival. (B) Relapse-free survival. (TIFF 11035 kb)
10434_2016_5702_MOESM7_ESM.tif
Figure S5 Kaplan–Meier analysis of overall survival of patients with clear-cell renal cell carcinoma (ccRCC) based on mast cells infiltration with TCGA cohort according to LM22 genotype profile. P value was calculated by log-rank test. (TIFF 8352 kb)
10434_2016_5702_MOESM8_ESM.tif
Literatur
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