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Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma

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Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

An Erratum to this article was published on 17 January 2008

Abstract

Purpose

Determination of marker for identification of oral squamous cell carcinoma (OSCC) is important for early diagnosis and individual therapy. Cytokeratins (CKs) like CK 19 and CK 20 are known to be useful diagnostic and prognostic markers for solid tumors. The aim of this study was to evaluate the relevance of further CKs for diagnosis of OSCC.

Materials

In 10 OSCC and 5 normal mucosal samples, the expression patterns of 31 CK genes were examined by cDNA microarray in order to identify CKs with most pronounced over-expression. The results were verified for CK 17, CK 19, and CK 20 in addition to 46 OSCC samples by relative quantification (RQ) using SYBR green real-time reverse transcriptase polymerase chain reaction (RT qPCR). A correlation of the CK expressions with the tumor classification was carried out.

Results

cDNA microarray analyses showed that out of all CKs, CK 17 was up-regulated strongest in OSCC compared to normal samples, and over-expression was most significantly associated with diagnosis (P = 0.002). Expression rates of CK 19 and CK 20 were not significantly different between OSCC samples and normal samples. In 56 samples analyzed by real-time RT qPCR, CK 17 was over-expressed in 53 (94.6%), CK 19 in 18 (32.1%), and CK 20 in 7 (12.5%). The over-expression of CK 17 was significantly associated with metastases of neck lymph nodes (P < 0.05). CK 19 was significantly over-expressed in T3 and T4 OSCC, in stage III and IV patients (P < 0.05), and in poorly differentiated OSCC (P < 0.03). The over-expression of CK 20 was significantly associated with metastases of neck lymph nodes (P < 0.03). Determined by RQ, the mean value of CK 17 over-expression was significantly higher than that of the other CKs (P < 0.01), and was significantly associated with T1 and T2 OSCC (P < 0.03) and with stage I and II patients (P < 0.01).

Conclusion

CK 19 might be linked to the clinical progression and differentiation of OSCC, and CK 20 could be associated with metastases of neck lymph nodes in OSCC. Due to the significant up-regulation and the strong over-expression, CK 17 might be the most suitable marker for diagnosis of OSCC out of the CK-family.

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References

  • Beger HG, Rau B, Gansauge F, Poch B, Link KH (2003) Treatment of pancreatic cancer: challenge of the facts. World J Surg 27:1075–1084

    Article  PubMed  Google Scholar 

  • Carrilho C, Alberto M, Buane L, David L (2004) Keratins 8, 10, 13, and 17 are useful markers in the diagnosis of human cervix carcinomas. Hum Pathol 35:546–551

    Article  PubMed  CAS  Google Scholar 

  • Christoph F, Weikert S, Wolff I, Schostak M, Tabiti K, Muller M, Miller K, Schrader M (2007) Urinary cytokeratin 20 mRNA expression has the potential to predict recurrence in superficial transitional cell carcinoma of the bladder. Cancer Lett 245:121–126

    Article  PubMed  CAS  Google Scholar 

  • Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM (2005) Immunohistochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol 29:359–367

    Article  PubMed  Google Scholar 

  • Cohen-Kerem R, Madah W, Sabo E, Rahat MA, Greenberg E, Elmalah I (2004) Cytokeratin-17 as a potential marker for squamous cell carcinoma of the larynx. Ann Otol Rhinol Laryngol 113:821–827

    PubMed  Google Scholar 

  • Elsheikh MN, Mahfouz ME, Elsheikh E (2005) Level IIb lymph nodes metastasis in elective supraomohyoid neck dissection for oral cavity squamous cell carcinoma: a molecular-based study. Laryngoscope 115:1636–1640

    Article  PubMed  Google Scholar 

  • Garrel R, Dromard M, Costes V, Barbotte E, Comte F, Gardiner Q, Cartier C, Makeieff M, Crampette L, Guerrier B, Boulle N (2006) The diagnostic accuracy of reverse transcription-PCR quantification of cytokeratin mRNA in the detection of sentinel lymph node invasion in oral and oropharyngeal squamous cell carcinoma: a comparison with immunohistochemistry. Clin Cancer Res 12:2498–2505

    Article  PubMed  CAS  Google Scholar 

  • Goldstein NS, Bassi D (2001) Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am J Clin Pathol 115:695–702

    Article  PubMed  CAS  Google Scholar 

  • Hamakawa H, Bao Y, Takarada M, Fukuyumi M, Tanioka H (1998) Cytokeratin expression in squamous cell carcinoma of the lung and oral cavity: an immunohistochemical study with possible clinical relevance. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 85:438–443

    Article  PubMed  CAS  Google Scholar 

  • Hashimoto T, Kobayashi Y, Ishikawa Y, Tsuchiya S, Okumura S, Nakagawa K, Tokuchi Y, Hayashi M, Nishida K, Hayashi S, Hayashi J, Tsuchiya E (2002) Prognostic value of genetically diagnosed lymph node micrometastasis in non-small cell lung carcinoma cases. Cancer Res 60:6472–6478

    Google Scholar 

  • Hsiao LL, Dangond F, Yoshida T, Hong R, Jensen RV, Misra J, Dillon W, Lee KF, Clark KE, Haverty P, Weng Z, Mutter GL, Frosch MP, Macdonald ME, Milford EL, Crum CP, Bueno R, Pratt RE, Mahadevappa M, Warrington JA, Stephanopoulos G, Stephanopoulos G, Gullans SR (2001) A compendium of gene expression in normal human tissues. Physiol Genomics 7:97–104

    PubMed  CAS  Google Scholar 

  • Kawamata H, Uchida D, Nakashiro K, Hino S, Omotehara F, Yoshida H, Sato M (1999) Haematogenous cytokeratin 20 mRNA as a predictive marker for recurrence in oral cancer patients. Br J Cancer 80:448–452

    Article  PubMed  CAS  Google Scholar 

  • Kijima F, Natsugoe S, Takao S, Aridome K, Baba M, Yoshifumi M, Eizuru Y, Aikou T (2000) Detection and clinical significance of lymph node micrometastasis determined by reverse transcription-polymerase chain reaction in patients with esophageal carcinoma. Oncology 58:38–44

    Article  PubMed  CAS  Google Scholar 

  • Kubota K, Nakanishi H, Hiki N, Shimizu N, Tsuji E, Yamaguchi H, Mafune K, Tange T, Tatematsu M, Kaminishi M (2003) Quantitative detection of micrometastases in the lymph nodes of gastric cancer patients with real-time RT-PCR: a comparative study with immunohistochemistry. Int J Cancer 105:136–143

    Article  PubMed  CAS  Google Scholar 

  • Liefers GJ, Cleton-Jansen AM, van de Velde CJ, Hermans J, van Krieken JH, Cornelisse CJ, Tollenaar RA (1998) Micrometastases and survival in stage II colorectal cancer. N Engl J Med 339:223–228

    Article  PubMed  CAS  Google Scholar 

  • Lindberg K, Rheinwald JG (1989) Suprabasal 40 kd keratin (K19) expression as an immunohistologic marker of premalignancy in oral epithelium. Am J Pathol 134:89–98

    PubMed  CAS  Google Scholar 

  • Maddox P, Sasieni P, Szarewski A, Anderson M, Hanby A (1999) Differential expression of keratins 10, 17, and 19 in normal cervical epithelium, cervical intraepithelial neoplasia, and cervical carcinoma. J Clin Pathol 52:41–46

    PubMed  CAS  Google Scholar 

  • Martens J, Baars J, Smedts F, Holterheus M, Kok MJ, Vooijs P, Ramaekers F (1999) Can keratin 8 and 17 immunohistochemistry be of diagnostic value in cervical cytology? A feasibility study. Cancer 87:87–92

    Article  PubMed  CAS  Google Scholar 

  • Mohr C (1997) Report on the 27th annual meeting of the German-Austrian-Swiss Working Group for tumors of the maxillofacial area. Mund Kiefer Gesichtschir 1:125–126

    Article  PubMed  CAS  Google Scholar 

  • Moll R, Zimbelmann R, Goldschmidt MD, Keith M, Laufer J, Kasper M, Koch PJ, Franke WW (1993) The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. Differentiation 53:75–93

    Article  PubMed  CAS  Google Scholar 

  • Okada Y, Fujiwara Y, Yamamoto H, Sugita Y, Yasuda T, Doki Y, Tamura S, Yano M, Shiozaki H, Matsuura N, Monden M (2001) Genetic detection of lymph node micrometastases in patients with gastric carcinoma by multiple-marker reverse transcriptase-polymerase chain reaction assay. Cancer 92:2056–2064

    Article  PubMed  CAS  Google Scholar 

  • Ram Prassad VV, Nirmala NR, Kotian MS (2005) Immunohistochemical evaluation of expression of cytokeratin 19 in different histological grades of leukoplakia and oral squamous cell carcinoma. Indian J Dent Res 16:6–11

    PubMed  CAS  Google Scholar 

  • Roepman P, Wessels LF, Kettelarij N, Kemmeren P, Miles AJ, Lijnzaad P, Tilanus MG, Koole R, Hordijk GJ, van der Vliet PC, Reinders MJ, Slootweg PJ, Holstege FC (2005) An expression profile for diagnosis of lymph node metastases from primary head and neck squamous cell carcinomas. Nat Genet 37:182–186

    Article  PubMed  CAS  Google Scholar 

  • Smedts F, Ramaekers F, Troyanovsky S, Pruszczynski M, Link M, Lane B, Leigh I, Schijf C, Vooijs P (1992) Keratin expression in cervical cancer. Am J Pathol 141:497–511

    PubMed  CAS  Google Scholar 

  • Soeth E, Grigoleit U, Moellmann B, Roder C, Schniewind B, Kremer B, Kalthoff H, Vogel I (2005) Detection of tumor cell dissemination in pancreatic ductal carcinoma patients by CK 20 RT-PCR indicates poor survival. J Cancer Res Clin Oncol 131:669–676

    Article  PubMed  Google Scholar 

  • van de Rijn M, Perou CM, Tibshirani R, Haas P, Kallioniemi O, Kononen J, Torhorst J, Sauter G, Zuber M, Kochli OR, Mross F, Dieterich H, Seitz R, Ross D, Botstein D, Brown P (2002) Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 161:1991–1996

    PubMed  Google Scholar 

  • Zhong LP, Chen WT, Zhang CP, Zhang ZY (2007) Increased CK19 expression correlated with pathologic differentiation grade and prognosis in oral squamous cell carcinoma patients. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 104:377–384

    Article  PubMed  Google Scholar 

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Acknowledgment

This study was supported by a grant of the Johannes und Frieda Marohn Stiftung Erlangen.

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Authors and Affiliations

  1. Department of Oral and Maxillofacial Surgery, University of Erlangen-Nuremberg, Glueckstrasse 11, 91054 , Erlangen, Germany

    Takeshi Toyoshima, Emeka Nkenke, Karl Andreas Schlegel, Friedrich Wilhelm Neukam & Jutta Ries

  2. Department of Oral and Maxillofacial Surgery, University of Athens, Vas. Sofias 93 and Dim. Soutsou 1, Athens, 11521, Greece

    Eleftherios Vairaktaris

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  1. Takeshi Toyoshima
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  2. Eleftherios Vairaktaris
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  3. Emeka Nkenke
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  6. Jutta Ries
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Correspondence to Jutta Ries.

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An erratum to this article can be found at http://dx.doi.org/10.1007/s00432-007-0350-6

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Toyoshima, T., Vairaktaris, E., Nkenke, E. et al. Cytokeratin 17 mRNA expression has potential for diagnostic marker of oral squamous cell carcinoma. J Cancer Res Clin Oncol 134, 515–521 (2008). https://doi.org/10.1007/s00432-007-0308-8

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  • DOI: https://doi.org/10.1007/s00432-007-0308-8

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