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01-03-2013 | Original Article

Clinical significance of peritumoral mast cells in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy

Authors: Susumu Saigusa, Koji Tanaka, Masaki Ohi, Yoshito Ishino, Hiromi Yasuda, Yoshinaga Okugawa, Yuji Toiyama, Yasuhiro Inoue, Keiichi Uchida, Yasuhiko Mohri, Masato Kusunoki

Published in: Esophagus | Issue 1/2013

Abstract

Background

Neoadjuvant chemoradiotherapy (CRT) followed by surgery is the standard approach for locally advanced esophageal cancer. Recently, the microenvironment (including the host immune response) after conventional chemo- and/or radiotherapy has been highlighted. The aim of this preliminary study was to evaluate peritumoral mast cells (MCs) in esophageal squamous cell carcinoma (ESCC) after neoadjuvant CRT.

Methods

We obtained a total of twenty specimens from patients with ESCC who underwent neoadjuvant CRT (30–40 Gy; 5-fluorouracil plus cisplatin) followed by surgery. We evaluated the expression of tryptase by MCs, Foxp3 by regulatory T cells, CD8 by cytotoxic T cells, and microvessel density (MVD) using immunohistochemistry. We investigated the correlation between the sizes of these marker-positive cell populations surrounding residual tumor nests, MVD and CRP, and clinical outcome.

Results

Patients with a low number of peritumoral MCs more frequently had lymphatic invasion (P = 0.0191). There was no significant correlation among the sizes of the marker-positive cell populations. We observed a significant negative correlation between the number of MCs and preoperative CRP levels (P = 0.009). Low numbers of peritumoral MCs, high MVD, and a preoperative C-reactive protein of >0.5 mg/dL were significantly associated with poor overall survival (MCs: P = 0.0239; MVD: P = 0.0317; CRP: P = 0.0395).

Conclusion

Our results suggest that peritumoral MCs may be associated with prognosis in patients with ESCC after neoadjuvant CRT.

Stahl M, Stuschke M, Lehmann N, Meyer HJ, Walz MK, Seeber S, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma of the esophagus. J Clin Oncol. 2005;23:2310–7.PubMedCrossRef

Lv J, Cao XF, Zhu B, Ji L, Tao L, Wang DD. Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma. World J Gastroenterol. 2009;15:4962–8.PubMedCrossRef

Sjoquist KM, Burmeister BH, Smithers BM, Zalcberg JR, Simes RJ, Barbour A, et al. Survival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis. Lancet Oncol. 2011;12:681–92.PubMedCrossRef

van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, et al. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012;366:2074–84.PubMedCrossRef

Lesterhuis WJ, de Vries IJ, Aarntzen EA, de Boer A, Scharenborg NM, van de Rakt M, et al. A pilot study on the immunogenicity of dendritic cell vaccination during adjuvant oxaliplatin/capecitabine chemotherapy in colon cancer patients. Br J Cancer. 2010;103:1415–21.PubMedCrossRef

Obeid M, Tesniere A, Ghiringhelli F, Fimia GM, Apetoh L, Perfettini JL, et al. Calreticulin exposure dictates the immunogenicity of cancer cell death. Nat Med. 2007;13:54–61.PubMedCrossRef

Khazaie K, Blatner NR, Khan MW, Gounari F, Gounaris E, Dennis K, et al. The significant role of mast cells in cancer. Cancer Metastasis Rev. 2011;30:45–60.PubMedCrossRef

Cho Y, Miyamoto M, Kato K, Fukunaga A, Shichinohe T, Kawarada Y, et al. CD4+ and CD8+ T cells cooperate to improve prognosis of patients with esophageal squamous cell carcinoma. Cancer Res. 2003;63:1555–9.PubMed

Yoshioka T, Miyamoto M, Cho Y, Ishikawa K, Tsuchikawa T, Kadoya M, et al. Infiltrating regulatory T cell numbers is not a factor to predict patient’s survival in oesophageal squamous cell carcinoma. Br J Cancer. 2008;98:1258–63.PubMedCrossRef

10.

Tsuchikawa T, Md MM, Yamamura Y, Shichinohe T, Hirano S, Kondo S. The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma. Ann Surg Oncol. 2012;19:1713–9.PubMedCrossRef

11.

Rao KN, Brown MA. Mast cells: multifaceted immune cells with diverse roles in health and disease. Ann N Y Acad Sci. 2008;1143:83–104.PubMedCrossRef

12.

Ribatti D, Crivellato E. Mast cells, angiogenesis, and tumour growth. Biochim Biophys Acta. 2012;1822:2–8.PubMedCrossRef

13.

Crivellato E, Nico B, Ribatti D. Mast cells and tumour angiogenesis: new insight from experimental carcinogenesis. Cancer Lett. 2008;269:1–6.PubMedCrossRef

14.

Gulubova M, Vlaykova T. Prognostic significance of mast cell number and microvascular density for the survival of patients with primary colorectal cancer. J Gastroenterol Hepatol. 2009;24:1265–75.PubMedCrossRef

15.

Yodavudh S, Tangjitgamol S, Puangsa-art S. Prognostic significance of microvessel density and mast cell density for the survival of Thai patients with primary colorectal cancer. J Med Assoc Thai. 2008;91:723–32.PubMed

16.

Tomita M, Matsuzaki Y, Edagawa M, Shimizu T, Hara M, Sekiya R, et al. Association of mast cells with tumor angiogenesis in esophageal squamous cell carcinoma. Dis Esophagus. 2001;14:135–8.PubMedCrossRef

17.

Carlini MJ, Dalurzo MC, Lastiri JM, Smith DE, Vasallo BC, Puricelli LI, et al. Mast cell phenotypes and microvessels in non-small cell lung cancer and its prognostic significance. Hum Pathol. 2010;41:697–705.PubMedCrossRef

18.

Elpek GO, Gelen T, Aksoy NH, Erdogan A, Dertsiz L, Demircan A, et al. The prognostic relevance of angiogenesis and mast cells in squamous cell carcinoma of the oesophagus. J Clin Pathol. 2001;54:940–4.PubMedCrossRef

19.

Nielsen HJ, Hansen U, Christensen IJ, Reimert CM, Brunner N, Moesgaard F. Independent prognostic value of eosinophil and mast cell infiltration in colorectal cancer tissue. J Pathol. 1999;189:487–95.PubMedCrossRef

20.

Welsh TJ, Green RH, Richardson D, Waller DA, O’Byrne KJ, Bradding P. Macrophage and mast-cell invasion of tumor cell islets confers a marked survival advantage in non-small-cell lung cancer. J Clin Oncol. 2005;23:8959–67.PubMedCrossRef

21.

Ali G, Boldrini L, Lucchi M, Picchi A, Dell’Omodarme M, Prati MC, et al. Treatment with interleukin-2 in malignant pleural mesothelioma: immunological and angiogenetic assessment and prognostic impact. Br J Cancer. 2009;101:1869–75.PubMedCrossRef

22.

Fleischmann A, Schlomm T, Kollermann J, Sekulic N, Huland H, Mirlacher M, et al. Immunological microenvironment in prostate cancer: high mast cell densities are associated with favorable tumor characteristics and good prognosis. Prostate. 2009;69:976–81.PubMedCrossRef

23.

Dabiri S, Huntsman D, Makretsov N, Cheang M, Gilks B, Bajdik C, et al. The presence of stromal mast cells identifies a subset of invasive breast cancers with a favorable prognosis. Mod Pathol. 2004;17:690–5.PubMedCrossRef

24.

Theoharides TC, Conti P. Mast cells: the Jekyll and Hyde of tumor growth. Trends Immunol. 2004;25:235–41.PubMedCrossRef

25.

Ju MJ, Qiu SJ, Gao Q, Fan J, Cai MY, Li YW, et al. Combination of peritumoral mast cells and T-regulatory cells predicts prognosis of hepatocellular carcinoma. Cancer Sci. 2009;100:1267–74.PubMedCrossRef

26.

Piconese S, Gri G, Tripodo C, Musio S, Gorzanelli A, Frossi B, et al. Mast cells counteract regulatory T-cell suppression through interleukin-6 and OX40/OX40L axis toward Th17-cell differentiation. Blood. 2009;114:2639–48.PubMedCrossRef

27.

Frossi B, D’Inca F, Crivellato E, Sibilano R, Gri G, Mongillo M, et al. Single-cell dynamics of mast cell-CD4+ CD25+ regulatory T cell interactions. Eur J Immunol. 2011;41:1872–82.PubMedCrossRef

28.

Ganeshan K, Bryce PJ. Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-beta. J Immunol. 2012;188:594–603.PubMedCrossRef

29.

Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73:2680–6.PubMedCrossRef

30.

Kassouf W, Agarwal PK, Herr HW, Munsell MF, Spiess PE, Brown GA, et al. Lymph node density is superior to TNM nodal status in predicting disease-specific survival after radical cystectomy for bladder cancer: analysis of pooled data from MDACC and MSKCC. J Clin Oncol. 2008;26:121–6.PubMedCrossRef

31.

Ogino S, Shima K, Baba Y, Nosho K, Irahara N, Kure S, et al. Colorectal cancer expression of peroxisome proliferator-activated receptor gamma (PPARG, PPARgamma) is associated with good prognosis. Gastroenterology. 2009;136:1242–50.PubMedCrossRef

32.

Tinge B, Molin D, Bergqvist M, Ekman S, Bergstrom S. Mast cells in squamous cell esophageal carcinoma and clinical parameters. Cancer Genomics Proteomics. 2010;7:25–9.PubMed

33.

Frungieri MB, Weidinger S, Meineke V, Kohn FM, Mayerhofer A. Proliferative action of mast-cell tryptase is mediated by PAR2, COX2, prostaglandins, and PPARgamma: possible relevance to human fibrotic disorders. Proc Natl Acad Sci USA. 2002;99:15072–7.

34.

Maltby S, Khazaie K, McNagny KM. Mast cells in tumor growth: angiogenesis, tissue remodelling and immune-modulation. Biochim Biophys Acta. 2009;1796:19–26.PubMed

35.

Allin KH, Nordestgaard BG. Elevated C-reactive protein in the diagnosis, prognosis, and cause of cancer. Crit Rev Clin Lab Sci. 2011;48:155–70.PubMedCrossRef

36.

Fujimoto T, Sato Y, Sasaki N, Teshima R, Hanaoka K, Kitani S. The canine mast cell activation via CRP. Biochem Biophys Res Commun. 2003;301:212–7.PubMedCrossRef

Title: Clinical significance of peritumoral mast cells in esophageal squamous cell carcinoma with neoadjuvant chemoradiotherapy
Authors: Susumu Saigusa
Koji Tanaka
Masaki Ohi
Yoshito Ishino
Hiromi Yasuda
Yoshinaga Okugawa
Yuji Toiyama
Yasuhiro Inoue
Keiichi Uchida
Yasuhiko Mohri
Masato Kusunoki
Publication date: 01-03-2013
Publisher: Springer Japan
Published in: Esophagus / Issue 1/2013
Print ISSN: 1612-9059
Electronic ISSN: 1612-9067
DOI: https://doi.org/10.1007/s10388-012-0356-2

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