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Heterogeneous ribonucleoprotein K is a marker of oral leukoplakia and correlates with poor prognosis of squamous cell carcinoma
Author(s) -
Matta Ajay,
Tripathi Satyendra Chandra,
DeSouza Leroi V.,
Grigull Jörg,
Kaur Jatinder,
Chauhan Shyam Singh,
Srivastava Anurag,
Thakar Alok,
Shukla Nootan Kumar,
Duggal Ritu,
DattaGupta Siddhartha,
Ralhan Ranju,
Michael Siu K.W.
Publication year - 2009
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.24517
Subject(s) - leukoplakia , malignancy , ribonucleoprotein , pathology , malignant transformation , cancer , medicine , immunohistochemistry , clinical significance , carcinoma , cancer research , biology , rna , gene , biochemistry
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