The purpose of this study is to investigate the clinical/prognostic significance of tumor-infiltrating mast cells (TIMs) in patients with colorectal cancer (CRC). TIM infiltration in 325 stage I to III CRC specimens was detected by immunohistochemistry. The optimal cutpoint of TIM density was assessed by the X-tile program. TIM infiltration in CRC was significantly higher than in normal colorectal tissues. According to the X-tile program, the cutpoint for high TIM infiltration in CRC was determined when TIM density was more than 8.0 per high-power field. Correlation analysis between TIM density and clinicopathological variables demonstrated that TIM infiltration was significantly associated with gender, nodal status, and American Joint Committee on Cancer stage. Multivariate Cox regression analysis showed that high TIM infiltration was a risk factor for both overall survival and disease-free survival. Taken together, high TIM infiltration can be an independent and useful biomarker for predicting the poor survival of patients with CRC.
JemalABrayFCenterMMFerlayJWardEFormanD.Global cancer statistics. CA Cancer J Clin. 2011;61:69-90.
2.
HuangYLiWChuD. Overexpression of matrix metalloproteinase-21 is associated with poor overall survival of patients with colorectal cancer. J Gastrointest Surg. 2011;15:1188-1194.
3.
HanahanDWeinbergRA.Hallmarks of cancer: the next generation. Cell. 2011;144:646-674.
4.
EadenJAAbramsKRMayberryJF.The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut. 2001;48: 526-535.
5.
HeijmansJBullerNVMuncanVvan den BrinkGR.Role of mast cells in colorectal cancer development, the jury is still out. Biochim Biophys Acta. 2012;1822:9-13.
6.
StrouchMJCheonECSalabatMR. Crosstalk between mast cells and pancreatic cancer cells contributes to pancreatic tumor progression. Clin Cancer Res. 2010;16:2257-2265.
7.
ChangDZMaYJiB. Mast cells in tumor microenvironment promotes the in vivo growth of pancreatic ductal adenocarcinoma. Clin Cancer Res. 2011;17:7015-7023.
8.
JohanssonARudolfssonSHammarstenP. Mast cells are novel independent prognostic markers in prostate cancer and represent a target for therapy. Am J Pathol. 2010;177:1031-1041.
9.
PittoniPTripodoCPiconeseS. Mast cell targeting hampers prostate adenocarcinoma development but promotes the occurrence of highly malignant neuroendocrine cancers. Cancer Res. 2011;71:5987-5997.
10.
MelilloRMGuarinoVAvillaE. Mast cells have a protumorigenic role in human thyroid cancer. Oncogene. 2010;29:6203-6215.
11.
JuMJQiuSJGaoQ. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci. 2009;100:1267-1274.
12.
AliGBoldriniLLucchiMMussiACorsiVFontaniniG.Tryptase mast cells in malignant pleural mesothelioma as an independent favorable prognostic factor. J Thorac Oncol. 2009;4:348-354.
13.
WelshTJGreenRHRichardsonDWallerDAO’ByrneKJBraddingP.Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23:8959-8967.
14.
RajputABTurbinDACheangMC. Stromal mast cells in invasive breast cancer are a marker of favourable prognosis: a study of 4,444 cases. Breast Cancer Res Treat. 2008;107:249-257.
15.
LiuJZhangYZhaoJ. Mast cell: insight into remodeling a tumor microenvironment. Cancer Metastasis Rev. 2011;30:177-184.
16.
MaltbySKhazaieKMcNagnyKM.Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta. 2009;1796:19-26.
17.
PagesFGalonJDieu-NosjeanMCTartourESautes-FridmanCFridmanWH.Immune infiltration in human tumors: a prognostic factor that should not be ignored. Oncogene. 2010;29:1093-1102.
18.
CampRLDolled-FilhartMRimmDL.X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10: 7252-7259.
19.
CaiMYHouJHRaoHL. High expression of H3K27me3 in human hepatocellular carcinomas correlates closely with vascular invasion and predicts worse prognosis in patients. Mol Med. 2011;17:12-20.
20.
RaesideDE.Monte Carlo principles and applications. Phys Med Biol. 1976;21:181-197.
21.
O’ConnellJBMaggardMAKoCY.Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst. 2004;96:1420-1425.
22.
NagtegaalIDQuirkeP.Revised staging: is it really better, or do we not know?J Clin Oncol. 2010;28:e397-e398; author reply e399-e400.
23.
RattoCRicciR.Potential pitfalls concerning colorectal cancer classification in the seventh edition of the AJCC Cancer Staging Manual. Dis Colon Rectum. 2011;54:e232.
24.
ThirunavukarasuPSukumarSSathaiahM. C-stage in colon cancer: implications of carcinoembryonic antigen biomarker in staging, prognosis, and management. J Natl Cancer Inst. 2011;103:689-697.
25.
GalonJCostesASanchez-CaboF. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science. 2006;313:1960-1964.
26.
PagesFBergerACamusM. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med. 2005;353:2654-2666.
27.
PagesFKirilovskyAMlecnikB. In situ cytotoxic and memory T cells predict outcome in patients with early-stage colorectal cancer. J Clin Oncol. 2009;27:5944-5951.
28.
LaghiLBianchiPMirandaE. CD3+ cells at the invasive margin of deeply invading (pT3-T4) colorectal cancer and risk of post-surgical metastasis: a longitudinal study. Lancet Oncol. 2009;10:877-884.
29.
KimMSChaeHJShinTYKimHMKimHR.Estrogen regulates cytokine release in human mast cells. Immunopharmacol Immunotoxicol. 2001;23:495-504.
30.
TaskinenMKarjalainen-LindsbergMLLeppaS.Prognostic influence of tumor-infiltrating mast cells in patients with follicular lymphoma treated with rituximab and CHOP. Blood. 2008;111:4664-4667.
QuZHuangXAhmadiP. Synthesis of basic fibroblast growth factor by murine mast cells: regulation by transforming growth factor beta, tumor necrosis factor alpha, and stem cell factor. Int Arch Allergy Immunol. 1998;115:47-54.
33.
RakusanKSarkarKTurekZWickerP.Mast cells in the rat heart during normal growth and in cardiac hypertrophy. Circ Res. 1990;66:511-516.
34.
ShinKNigrovicPACrishJ. Mast cells contribute to autoimmune inflammatory arthritis via their tryptase/heparin complexes. J Immunol. 2009;182:647-656.
35.
CoussensLMWerbZ.Matrix metalloproteinases and the development of cancer. Chem Biol. 1996;3:895-904.
36.
LuLFLindEFGondekDC. Mast cells are essential intermediaries in regulatory T-cell tolerance. Nature. 2006;442:997-1002.
37.
GounarisEErdmanSERestainoC. Mast cells are an essential hematopoietic component for polyp development. Proc Natl Acad Sci U S A. 2007;104:19977-19982.
38.
FisherERPaikSMRocketteHJonesJCaplanRFisherB.Prognostic significance of eosinophils and mast cells in rectal cancer: findings from the National Surgical Adjuvant Breast and Bowel Project (protocol R-01). Hum Pathol. 1989;20:159-163.
39.
AcikalinMFOnerUTopcuIYasarBKiperHColakE.Tumour angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas. Dig Liver Dis. 2005;37:162-169.
40.
GulubovaMVlaykovaT.Prognostic significance of mast cell number and microvascular density for the survival of patients with primary colorectal cancer. J Gastroenterol Hepatol. 2009;24:1265-1275.
41.
XiaQWuXJZhouQ. No relationship between the distribution of mast cells and the survival of stage IIIB colon cancer patients. J Transl Med. 2011;9:88.
42.
YodavudhSTangjitgamolSPuangsa-artS.Prognostic significance of microvessel density and mast cell density for the survival of Thai patients with primary colorectal cancer. J Med Assoc Thai. 2008;91:723-732.
43.
NielsenHJHansenUChristensenIJReimertCMBrunnerNMoesgaardF.Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue. J Pathol. 1999;189:487-495.
