Skip to main content
Erschienen in: Virchows Archiv 5/2013

01.11.2013 | Original Article

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

verfasst von: Renjie Chen, Meiping Lu, Jun Wang, Dawei Zhang, Hong Lin, Huijun Zhu, Weiming Zhang, Lin Xiong, Jun Ma, Yuan Mao, Jin Zhu, Jiaren Xu

Erschienen in: Virchows Archiv | Ausgabe 5/2013

Einloggen, um Zugang zu erhalten

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.
Literatur
1.
Zurück zum Zitat 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 462:399–407CrossRef 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 462:399–407CrossRef
2.
Zurück zum Zitat 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 450:355–8PubMedCrossRef 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 450:355–8PubMedCrossRef
3.
Zurück zum Zitat Aozasa K, Takakuwa T, Hongyo T, Yang WI (2008) Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol 87:110–117PubMedCrossRef Aozasa K, Takakuwa T, Hongyo T, Yang WI (2008) Nasal NK/T-cell lymphoma: epidemiology and pathogenesis. Int J Hematol 87:110–117PubMedCrossRef
4.
Zurück zum Zitat 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 138:435–447PubMedCrossRef 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 138:435–447PubMedCrossRef
5.
Zurück zum Zitat 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, Lyon 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, Lyon
6.
Zurück zum Zitat Al-Hakeem DA, Fedele S, Carlos R, Porter S (2007) Extranodal NK/T-cell lymphoma, nasal type. Oral Oncol 43:4–14PubMedCrossRef Al-Hakeem DA, Fedele S, Carlos R, Porter S (2007) Extranodal NK/T-cell lymphoma, nasal type. Oral Oncol 43:4–14PubMedCrossRef
7.
Zurück zum Zitat 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 128:579–584PubMedCrossRef 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 128:579–584PubMedCrossRef
8.
Zurück zum Zitat Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463PubMedCrossRef Egger G, Liang G, Aparicio A, Jones PA (2004) Epigenetics in human disease and prospects for epigenetic therapy. Nature 429:457–463PubMedCrossRef
9.
Zurück zum Zitat 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 60:656–660PubMedCrossRef 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 60:656–660PubMedCrossRef
10.
Zurück zum Zitat 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 78:5147–5150PubMedCrossRef 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 78:5147–5150PubMedCrossRef
11.
Zurück zum Zitat Ripani E, Sacchetti A, Corda D, Alberti S (1998) Human Trop-2 is a tumor-associated calcium signal transducer. Int J Cancer 76:671–676PubMedCrossRef Ripani E, Sacchetti A, Corda D, Alberti S (1998) Human Trop-2 is a tumor-associated calcium signal transducer. Int J Cancer 76:671–676PubMedCrossRef
12.
Zurück zum Zitat Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063PubMedCrossRef Ohmachi T, Tanaka F, Mimori K, Inoue H, Yanaga K, Mori M (2006) Clinical significance of TROP2 expression in colorectal cancer. Clin Cancer Res 12:3057–3063PubMedCrossRef
13.
Zurück zum Zitat 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 30:2497–2503PubMed 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 30:2497–2503PubMed
14.
Zurück zum Zitat 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 21:186–191PubMed 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 21:186–191PubMed
15.
Zurück zum Zitat 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 7:280–285PubMedCrossRef 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 7:280–285PubMedCrossRef
16.
Zurück zum Zitat 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 99:1290–1295PubMedCrossRef 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 99:1290–1295PubMedCrossRef
17.
Zurück zum Zitat 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 24:875–884PubMedCrossRef 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 24:875–884PubMedCrossRef
18.
Zurück zum Zitat 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 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
19.
Zurück zum Zitat 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 94:73–78PubMedCrossRef 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 94:73–78PubMedCrossRef
20.
Zurück zum Zitat 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 13:2208–2218PubMedCrossRef 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 13:2208–2218PubMedCrossRef
21.
Zurück zum Zitat 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 7:178PubMedCrossRef 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 7:178PubMedCrossRef
22.
Zurück zum Zitat 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 31:101PubMedCrossRef 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 31:101PubMedCrossRef
23.
Zurück zum Zitat 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 46:944–953PubMedCrossRef 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 46:944–953PubMedCrossRef
24.
Zurück zum Zitat 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 62:152–158PubMedCrossRef 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 62:152–158PubMedCrossRef
25.
Zurück zum Zitat 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 112:1029–1035PubMedCrossRef 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 112:1029–1035PubMedCrossRef
26.
Zurück zum Zitat 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 11:4357–4364PubMedCrossRef 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 11:4357–4364PubMedCrossRef
27.
Zurück zum Zitat 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 84:320–331PubMedCrossRef 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 84:320–331PubMedCrossRef
28.
Zurück zum Zitat 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 75:324–330PubMedCrossRef 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 75:324–330PubMedCrossRef
29.
Zurück zum Zitat 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 101:353–359PubMedCrossRef 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 101:353–359PubMedCrossRef
Metadaten
Titel
Increased expression of Trop2 correlates with poor survival in extranodal NK/T cell lymphoma, nasal type
verfasst von
Renjie Chen
Meiping Lu
Jun Wang
Dawei Zhang
Hong Lin
Huijun Zhu
Weiming Zhang
Lin Xiong
Jun Ma
Yuan Mao
Jin Zhu
Jiaren Xu
Publikationsdatum
01.11.2013
Verlag
Springer Berlin Heidelberg
Erschienen in
Virchows Archiv / Ausgabe 5/2013
Print ISSN: 0945-6317
Elektronische ISSN: 1432-2307
DOI
https://doi.org/10.1007/s00428-013-1475-4

Weitere Artikel der Ausgabe 5/2013

Virchows Archiv 5/2013 Zur Ausgabe

Neu im Fachgebiet Pathologie

Molekularpathologische Untersuchungen im Wandel der Zeit

Open Access Biomarker Leitthema

Um auch an kleinen Gewebeproben zuverlässige und reproduzierbare Ergebnisse zu gewährleisten ist eine strenge Qualitätskontrolle in jedem Schritt des Arbeitsablaufs erforderlich. Eine nicht ordnungsgemäße Prüfung oder Behandlung des …

Vergleichende Pathologie in der onkologischen Forschung

Pathologie Leitthema

Die vergleichende experimentelle Pathologie („comparative experimental pathology“) ist ein Fachbereich an der Schnittstelle von Human- und Veterinärmedizin. Sie widmet sich der vergleichenden Erforschung von Gemeinsamkeiten und Unterschieden von …

Gastrointestinale Stromatumoren

Open Access GIST CME-Artikel

Gastrointestinale Stromatumoren (GIST) stellen seit über 20 Jahren ein Paradigma für die zielgerichtete Therapie mit Tyrosinkinaseinhibitoren dar. Eine elementare Voraussetzung für eine mögliche neoadjuvante oder adjuvante Behandlung bei …

Personalisierte Medizin in der Onkologie

Aufgrund des erheblichen technologischen Fortschritts in der molekularen und genetischen Diagnostik sowie zunehmender Erkenntnisse über die molekulare Pathogenese von Krankheiten hat in den letzten zwei Jahrzehnten ein grundlegender …