Open AccessPredictive value of the combination of SMAD4 expression and lymphocyte infiltration in malignant transformation of oral leukoplakia
Author(s) -
Sakata Junki,
Yoshida Ryoji,
Matsuoka Yuichiro,
Nagata Masashi,
Hirosue Akiyuki,
Kawahara Kenta,
Nakamura Takuya,
Nakamoto Masafumi,
Hirayama Masatoshi,
Takahashi Nozomu,
Nakashima Hikaru,
Arita Hidetaka,
Ogi Hidenao,
Hiraki Akimitsu,
Shinohara Masanori,
Nakayama Hideki
Publication year - 2017
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.1005
Subject(s) - stromal cell , smad , malignant transformation , immunohistochemistry , medicine , infiltration (hvac) , lymphocyte , pathology , cancer research , transforming growth factor , oncology , physics , thermodynamics
Oral leukoplakia ( OL ) is a common, potentially malignant disorder of the oral cavity. SMAD 4 was initially identified as a tumor suppressor and central mediator of transforming growth factor ( TGF )‐ β signaling. In this study, we aimed to determine the expression patterns of SMAD 4 in OL , its relationship with the degree of inflammation, and its clinical implications as a biomarker for OL malignant transformation. A total of 150 patients with OL were enrolled in this study. Paraffin‐embedded sections obtained from biopsy or resection specimens were subjected to immunohistochemical analysis. Associations among the status of epithelial SMAD 4 expression, stromal lymphocyte infiltration, and malignant transformation of OL were examined. Malignant transformation was significantly associated with the status of SMAD 4 expression ( P = 0.0017) and lymphocyte infiltration status ( P = 0.0054). Cox regression analysis, based on the event‐free survival ( EFS ), revealed that a low SMAD 4 expression was a significant prognostic factor in OL patients (hazard ratio, 2.632; P = 0.043). In addition, a low SMAD 4 expression was closely correlated with high lymphocyte infiltration ( P = 0.00035), resulting in a significant correlation between the combination of low SMAD 4 expression and high lymphocyte infiltration with malignant transformation of OL ( P = 0.00027). The combination of the status of epithelial SMAD 4 expression and stromal lymphocyte infiltration may be a useful biomarker for predicting malignant transformation in OL patients. These results suggest that not only epithelial SMAD 4 loss, but also stromal features, may regulate the risk of malignant transformation of OL .