DeltaNp63 overexpression, alone and in combination with other biomarkers, predicts the development of oral cancer in patients with leukoplakia.
OBJECTIVE
The risk of malignant transformation of oral preneoplastic lesion (OPL) is difficult to assess. DeltaNp63 is an early oncoprotein associated with mucosal tumorigenesis. The purpose of this study was to assess DeltaNp63 expression in OPL and its role as a marker of oral cancer risk.


METHODS
DeltaNp63 expression was determined using immunohistochemistry in 152 OPL patients included in a clinical trial comparing retinyl palmitate alone or plus beta-carotene with low-dose 13-cis-retinoic acid. The associations between DeltaNp63 expression as well as DeltaNp63 expression with other potential risk factors for oral cancer development were analyzed.


RESULTS
DeltaNp63 expression was positive in 41 (27%) patients, clusters of intraepithelial inflammatory cells (EIC) were noted in 37 (26%) patients, and podoplanin (previously reported) was positive in 56 (37%) patients. Significantly more patients whose lesions were DeltaNp63 positive or exhibited EIC developed oral cancers. In the multicovariate analysis including age, treatment, and histologic status as cofactors, positive DeltaNp63 expression was associated with an increased hazard ratio of 3.308 (95% confidence interval, 1.663-6.580; P = 0.0007). Patients whose lesions showed positive DeltaNp63, podoplanin, and EIC had the highest oral cancer risk with a hazard ratio of 4.372 (95% confidence interval, 1.912-9.992; P = 0.0005) and 61% oral cancer development rate at 5 years compared with 15% of other OPL patients (P < 0.0001).


CONCLUSIONS
DeltaNp63 overepression in OPL is associated with increased oral cancer risk. Together, DeltaNp63, podoplanin, and EIC may be used as biomarkers to identify OPL patients with substantially high oral cancer risk.
Saintigny
Pierre
P
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas M D Anderson Cancer Center, Houston, Texas, USA.
El-Naggar
Adel K
AK
Papadimitrakopoulou
Vali
V
Ren
Hening
H
Fan
You-Hong
YH
Feng
Lei
L
Lee
J Jack
JJ
Kim
Edward S
ES
Hong
Waun Ki
WK
Lippman
Scott M
SM
Mao
Li
L
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D004224:Diterpenes; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000473:pathology; D015474:Isotretinoin / Q000008:administration & dosage; D007972:Leukoplakia, Oral / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000517:prevention & control; D011379:Prognosis; D000084562:Retinyl Esters; D015534:Trans-Activators / Q000235:genetics*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D015854:Up-Regulation; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives; D019207:beta Carotene / Q000008:administration & dosage; D000098853:Podoplanin
D014408:Biomarkers, Tumor; D004224:Diterpenes; D015474:Isotretinoin; D008562:Membrane Glycoproteins; D000084562:Retinyl Esters; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D014801:Vitamin A; D019207:beta Carotene; C117468:PDPN protein, human; D000098853:Podoplanin; C115051:TP63 protein, human; C014794:retinol palmitate