Early Detection and Diagnosis

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Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma

  1. Ajay Matta1,2,†,
  2. Satyendra Chandra Tripathi3,†,
  3. Leroi V. DeSouza1,2,
  4. Jörg Grigull4,
  5. Jatinder Kaur3,
  6. Shyam Singh Chauhan3,
  7. Anurag Srivastava5,
  8. Alok Thakar6,
  9. Nootan Kumar Shukla7,
  10. Ritu Duggal8,
  11. Siddhartha DattaGupta9,
  12. Ranju Ralhan1,2,10,11,12,13,‡,§,*,
  13. K.W. Michael Siu1,2,‡

Article first published online: 22 APR 2009

DOI: 10.1002/ijc.24517

Issue

International Journal of Cancer

International Journal of Cancer

Volume 125, Issue 6, pages 1398–1406, 15 September 2009

Additional Information

How to Cite

Matta, A., Tripathi, S. C., DeSouza, L. V., Grigull, J., Kaur, J., Chauhan, S. S., Srivastava, A., Thakar, A., Shukla, N. K., Duggal, R., DattaGupta, S., Ralhan, R. and Michael Siu, K. (2009), Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma. International Journal of Cancer, 125: 1398–1406. doi: 10.1002/ijc.24517

Author Information

  1. 1

    Department of Chemistry, York University, Toronto, Ontario, Canada

  2. 2

    Centre for Research in Mass Spectrometry, York University, Toronto, Ontario, Canada

  3. 3

    Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India

  4. 4

    Department of Mathematics and Statistics, York University, Toronto, Ontario, Canada

  5. 5

    Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, India

  6. 6

    Department of Otorhinolaryngology, All India Institute of Medical Sciences, New Delhi, India

  7. 7

    Department of Surgery, Dr. B. R. A. Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India

  8. 8

    Department of Dental Surgery, All India Institute of Medical Sciences, New Delhi, India

  9. 9

    Department of Pathology, All India Institute of Medical Sciences, New Delhi, India

  10. 10

    Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases, Mount Sinai Hospital, Toronto, Ontario, Canada

  11. 11

    Department of Otolaryngology – Head and Neck Surgery, Mount Sinai Hospital, Toronto, Ontario, Canada

  12. 12

    Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada

  13. 13

    Department of Otolaryngology – Head and Neck Surgery, University of Toronto, Toronto, Ontario, Canada

  1. †

    The first two authors contributed equally to this study.

  2. ‡

    RR and KWMS are senior authors in this study.

  3. §

    Fax: +(416)736-5936.

*Centre for Research in Mass Spectrometry, Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, Canada M3J 1P3

Publication History

  1. Issue published online: 14 JUL 2009
  2. Article first published online: 22 APR 2009
  3. Manuscript Accepted: 26 MAR 2009
  4. Manuscript Received: 16 JAN 2009

Funded by

  • Canadian Institutes of Health Research (CIHR)
  • Ontario Research and Development Challenge Fund
  • Applied Biosystems/MDS Analytical Technologies

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Keywords:

  • hnRNP K;
  • oral leukoplakia;
  • squamous cell carcinoma;
  • head-and-neck cancer;
  • prognosis

Abstract

Oral leukoplakia is a heterogeneous lesion with risk of cancer development; there are no biomarkers to predict its potential of malignant transformation. Tissue proteomic analysis of oral leukoplakia using iTRAQ labeling liquid chromatography–mass spectrometry showed overexpression of heterogeneous ribonucleoprotein K (hnRNP K), a transformation-related RNA-binding protein, in leukoplakia in comparison with normal tissue. Herein, we investigated the clinical significance of hnRNP K in identification of oral leukoplakic lesions in early stages and as a prognostic marker in head-and-neck/oral squamous cell carcinomas (HNOSCCs). Immunohistochemical analysis of hnRNP K was performed in 100 HNOSCCs, 199 leukoplakias and 55 nonmalignant tissues and correlated with clinicopathologic parameters and disease prognosis over 6 years for HNOSCCs. hnRNP K nuclear expression increased from normal tissues to leukoplakia, and frank malignancy (p < 0.001). Cytoplasmic hnRNP K increased significantly from leukoplakia to HNOSCCs (p < 0.001) and was associated with poor prognosis of HNOSCCs (p = 0.011) by Kaplan–Meier analysis. The most important finding of our follow-up study is that cytoplasmic hnRNP K is an independent predictor of disease recurrence in HNOSCC patients. In conclusion, nuclear hnRNP K may serve as a potential marker for early diagnosis, whereas its cytoplasmic accumulation can help to identify a subgroup of HNOSCC patients with poor prognosis, suggesting its putative utility in clinical management of HNOSCC. © 2009 UICC

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