Virchows Archiv

, Volume 463, Issue 5, pp 713–719 | Cite as

Increased expression of Trop2 correlates with poor survival in extranodal NK/T cell lymphoma, nasal type

  • Renjie Chen
  • Meiping Lu
  • Jun Wang
  • Dawei Zhang
  • Hong Lin
  • Huijun Zhu
  • Weiming Zhang
  • Lin Xiong
  • Jun Ma
  • Yuan Mao
  • Jin Zhu
  • Jiaren Xu
Original Article

Abstract

Human trophoblastic cell surface antigen 2 (Trop2) has been suggested to play an important role in the development of solid tumors. However, the expression of Trop2 in extranodal NK/T cell lymphoma, nasal type (ENKTL) and the relationship with the clinical characteristics of this disease remain poorly understood. In this study, one-step quantitative PCR reverse transcription-polymerase chain reaction and immunohistochemical staining with tissue sections were employed to evaluate the expression of Trop2 in ENKTL. Furthermore, the relationship between Trop2 expression and prognosis of ENKTL was investigated. Expression of Trop2 mRNA and protein was significantly higher in ENKTL tissue than in corresponding non-lymphomatous tissue (p = 0.04 and p < 0.001, respectively). Expression of Trop2 protein in ENKTL was associated with lymph node involvement and poor overall survival (p = 0.045 and p = 0.018, respectively). Kaplan–Meier analysis and the logrank test indicated that lymph node involvement (p = 0.0481), single therapy strategy (p = 0.0037), and high expression of Trop2 (p = 0.0042) are significantly correlated with poor prognosis of ENKTL patients. The data suggest that Trop2 expression reflects a more malignant phenotype and may serve as an unfavorable prognostic factor for ENKTL.

Keywords

Trop2 ENKTL qPCR Immunohistochemistry Tumor marker 

Notes

Acknowledgments

This work is supported in part by grants from the Director Foundation of the National Natural Science Foundation (No. 81241074), China and the Social Development and Applied Research Projects of Nantong (No.K2010054, No.K2010048), Nantong, China.

Conflict of interest

The authors have no conflicts of interest.

References

  1. 1.
    Kondo S, Tanimoto K, Yamada K, Yoshimoto G, Suematsu E, Fujisaki T, Oshiro Y, Tamura K, Takeshita M, Okamura S (2012) Mature T/NK-cell lymphoproliferative disease and Epstein-Barr virus infection are more frequent in patients with rheumatoid arthritis treated with methotrexate. Virchows Arch 462:399–407CrossRefGoogle Scholar
  2. 2.
    Gonin J, Kadiri H, Bensaci S, Le Tourneau A, Molina TJ, Diebold J, Abdellouche DJ, Audouin J (2007) Primary mediastinal anaplastic alk-1-positive large-cell lymphoma of T/NK-cell type expressing CD20. Virchows Arch 450:355–8PubMedCrossRefGoogle Scholar
  3. 3.
    Aozasa K, Takakuwa T, Hongyo T, Yang WI (2008) Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol 87:110–117PubMedCrossRefGoogle Scholar
  4. 4.
    Ren YL, Nong L, Zhang S, Zhao J, Zhang XM, Li T (2012) Analysis of 142 Northern Chinese patients with peripheral T/NK-Cell lymphomas: subtype distribution, clinicopathologic features, and prognosis. Am J Clin Pathol 138:435–447PubMedCrossRefGoogle Scholar
  5. 5.
    Jaffe ES, Harris NL, Stein H, Vardiman JW (2001) WHO classification of tumours. Volume 3: pathology and genetics of tumours of haematopoietic and lymphoid tissue. IARC, LyonGoogle Scholar
  6. 6.
    Al-Hakeem DA, Fedele S, Carlos R, Porter S (2007) Extranodal NK/T-cell lymphoma, nasal type. Oral Oncol 43:4–14PubMedCrossRefGoogle Scholar
  7. 7.
    Hsieh PP, Tung CL, Chan AB, Liao JB, Wang JS, Tseng HH, Su HH, Chang KC, Chang CC (2007) EBV viral load in tumor tissue is an important prognostic indicator for nasal NK/T-cell lymphoma. Am J Clin Pathol 128:579–584PubMedCrossRefGoogle Scholar
  8. 8.
    Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463PubMedCrossRefGoogle Scholar
  9. 9.
    Cabrera ME, Eizuru Y, Itoh T, Koriyama C, Tashiro Y, Ding S (2007) Nasal natural killer/T-cell lymphoma and its association with type “I”/XhoI loss strain Epstein–Barr virus in Chile. J Clin Pathol 60:656–660PubMedCrossRefGoogle Scholar
  10. 10.
    Lipinski M, Parks DR, Rouse RV, Herzenberg LA (1981) Human trophoblast cell-surface antigens defined by monoclonal antibodies. Proc Natl Acad Sci U S A 78:5147–5150PubMedCrossRefGoogle Scholar
  11. 11.
    Ripani E, Sacchetti A, Corda D, Alberti S (1998) Human Trop-2 is a tumor-associated calcium signal transducer. Int J Cancer 76:671–676PubMedCrossRefGoogle Scholar
  12. 12.
    Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063PubMedCrossRefGoogle Scholar
  13. 13.
    Sukhthankar M, Alberti S, Baek SJ (2010) (−)-Epigallocatechin-3-gallate (EGCG) post-transcriptionally and post-translationally suppresses the cell proliferative protein TROP2 in human colorectal cancer cells. Anticancer Res 30:2497–2503PubMedGoogle Scholar
  14. 14.
    Fong D, Spizzo G, Gostner JM, Gastl G, Moser P, Krammel C, Gerhard S, Rasse M, Laimer K (2008) TROP2: a novel prognostic marker in squamous cell carcinoma of the oral cavity. Mod Pathol 21:186–191PubMedGoogle Scholar
  15. 15.
    Wang J, Day R, Dong Y, Weintraub SJ, Michel L (2008) Identification of Trop-2 as an oncogene and an attractive therapeutic target in colon cancers. Mol Cancer Ther 7:280–285PubMedCrossRefGoogle Scholar
  16. 16.
    Fong D, Moser P, Krammel C, Gostner JM, Margreiter R, Mitterer M, Gastl G, Spizzo G (2008) High expression of TROP2 correlates with poor prognosis in pancreatic cancer. Br J Cancer 99:1290–1295PubMedCrossRefGoogle Scholar
  17. 17.
    Fang YJ, Lu ZH, Wang GQ, Pan ZZ, Zhou ZW, Yun JP, Zhang MF, Wan DS (2009) Elevated expressions of MMP7, TROP2, and survivin are associated with survival, disease recurrence, and liver metastasis of colon cancer. Int J Colorectal Dis 24:875–884PubMedCrossRefGoogle Scholar
  18. 18.
    Wu H, Xu H, Zhang S, Wang X, Zhu H, Zhang H, Zhu J, Huang J (2012) Potential therapeutic target and independent prognostic marker of TROP2 in laryngeal squamous cell carcinoma. Head Neck. doi:10.1002/hed.23138 Google Scholar
  19. 19.
    Lin H, Huang JF, Qiu JR, Zhang HL, Tang XJ, Li H, Wang CJ, Wang ZC, Feng ZQ, Zhu J (2012) Significantly upregulated TACSTD2 and Cyclin D1 correlate with poor prognosis of invasive ductal breast cancer. Exp Mol Pathol 94:73–78PubMedCrossRefGoogle Scholar
  20. 20.
    Mao Y, Zhang DW, Wen J, Cao Q, Chen RJ, Zhu J, Feng ZQ (2012) A novel LMP1 antibody synergizes with mitomycin C to inhibit nasopharyngeal carcinoma growth in vivo through inducing apoptosis and downregulating vascular endothelial growth factor. Int J Mol Sci 13:2208–2218PubMedCrossRefGoogle Scholar
  21. 21.
    Mao Y, Zhang DW, Zhu H, Lin H, Xiong L, Cao Q, Liu Y, Li QD, Xu JR, Xu LF, Chen RJ (2012) LMP1 and LMP2A are potential prognostic markers of extranodal NK/T-cell lymphoma, nasal type (ENKTL). Diagn Pathol 7:178PubMedCrossRefGoogle Scholar
  22. 22.
    Mao Y, Zhang DW, Lin H, Xiong L, Liu Y, Li QD, Ma J, Cao Q, Chen RJ, Zhu J, Feng ZQ (2012) Alpha B-crystallin is a new prognostic marker for laryngeal squamous cell carcinoma. J Exp Clin Cancer Res 31:101PubMedCrossRefGoogle Scholar
  23. 23.
    Bignotti E, Todeschini P, Calza S, Falchetti M, Ravanini M, Tassi RA, Ravaggi A, Bandiera E, Romani C, Zanotti L, Tognon G, Odicino FE, Facchetti F, Pecorelli S, Santin AD (2010) Trop-2 overexpression as an independent marker for poor overall survival in ovarian carcinoma patients. Eur J Cancer 46:944–953PubMedCrossRefGoogle Scholar
  24. 24.
    Mühlmann G, Spizzo G, Gostner J, Zitt M, Maier H, Moser P, Gastl G, Zitt M, Müller HM, Margreiter R, Ofner D, Fong D (2009) TROP2 expression as prognostic marker for gastric carcinoma. J Clin Pathol 62:152–158PubMedCrossRefGoogle Scholar
  25. 25.
    Nakashima K, Shimada H, Ochiai T, Kuboshima M, Kuroiwa N, Okazumi S, Matsubara H, Nomura F, Takiguchi M, Hiwasa T (2004) Serological identification of TROP2 by recombinant cDNA expression cloning using sera of patients with esophageal squamous cell carcinoma. Int J Cancer 112:1029–1035PubMedCrossRefGoogle Scholar
  26. 26.
    Huang H, Groth J, Sossey-Alaoui K, Hawthorn L, Beall S, Geradts J (2005) Aberrant expression of novel and previously described cell membrane markers in human breast cancer cell lines and tumors. Clin Cancer Res 11:4357–4364PubMedCrossRefGoogle Scholar
  27. 27.
    Kluger HM, Kluger Y, Gilmore-Hebert M, DiVito K, Chang JT, Rodov S, Mironenko O, Kacinski BM, Perkins AS, Sapi E (2004) cDNA microarray analysis of invasive and tumorigenic phenotypes in a breast cancer model. Lab Invest 84:320–331PubMedCrossRefGoogle Scholar
  28. 28.
    El Sewedy T, Fornaro M, Alberti S (1998) Cloning of the murine TROP2 gene: conservation of a PIP2-binding sequence in the cytoplasmic domain of TROP-2. Int J Cancer 75:324–330PubMedCrossRefGoogle Scholar
  29. 29.
    Mangino G, Grazia CM, Barnaba V, Alberti S (2002) Presentation of native TROP-2 tumor antigens to human cytotoxic T lymphocytes by engineered antigen-presenting cells. Int J Cancer 101:353–359PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Renjie Chen
    • 1
  • Meiping Lu
    • 2
  • Jun Wang
    • 3
  • Dawei Zhang
    • 1
  • Hong Lin
    • 4
  • Huijun Zhu
    • 5
  • Weiming Zhang
    • 6
  • Lin Xiong
    • 7
  • Jun Ma
    • 8
  • Yuan Mao
    • 9
  • Jin Zhu
    • 10
    • 11
  • Jiaren Xu
    • 3
  1. 1.Department of Otolaryngology-Head and Neck SurgeryThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  2. 2.Department of Otolaryngology-Head and Neck SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  3. 3.Department of Hematology and OncologyJiangsu Provincial HospitalNanjingChina
  4. 4.Jiangsu Provincial Blood CenterNanjingChina
  5. 5.Department of PathologyAffiliated Hospital of Nantong UniversityNantongChina
  6. 6.Department of PathologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  7. 7.Department of PathologyThe Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina
  8. 8.Department of Otolaryngology-Head and Neck SurgeryYiji Shan Hospital of Wannan Medical CollegeWuhuChina
  9. 9.Department of Otolaryngology-Head and Neck SurgeryJiangsu Provincial HospitalNanjingChina
  10. 10.Huadong Medical Institute of BiotechnologyNanjingChina
  11. 11.The Key Laboratory of Cancer Biomarkers, Prevention & Treatment Cancer Center and The Key Laboratory of Antibody Technique of Ministry of HealthNanjing Medical UniversityNanjingChina

Personalised recommendations