retinol-palmitate and Leukoplakia--Oral

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.. 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.. 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).. 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.

Topics: Antineoplastic Combined Chemotherapy Protocols; beta Carotene; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diterpenes; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Humans; Inflammation; Isotretinoin; Leukoplakia, Oral; Male; Membrane Glycoproteins; Middle Aged; Mouth Neoplasms; Prognosis; Retinyl Esters; Trans-Activators; Transcription Factors; Tumor Suppressor Proteins; Up-Regulation; Vitamin A

The aim of photodynamic diagnostics is complete visualization of all neoplastic lesions in a tumorous organ after the application of a tumor-selective photosensitizer. We explored the potential benefit of a combination of retinyl palmitate for the treatment of oral leukoplakias and follow-up diagnosis of malignant tissue by using 5-aminolevulinic acid (5-ALA) as a fluorescence marker. Semiquantitative measurements were performed following the topical application of 5-ALA in six patients. After biopsy and histological evaluation of tissue specimens the patients were treated with escalating doses of retinyl palmitate. After treatment periods ranging from 4 to 8 weeks 5-ALA was again applied for photodetection of persisting fluorescence. In all cases prior to retinyl palmitate treatment a prominent red fluorescence indicated tissue dysplasia. Eight weeks after treatment with retinyl palmitate decreased red fluorescence intensities were found, and repeated histological evaluations showed no persistent signs of dysplastic lesions. Our initial experience shows that high doses of retinyl palmitate can be useful for treating dysplastic lesions in the upper aerodigestive tract and can be monitored with 5-ALA induced protoporphyrin IX fluorescence.

Topics: Adult; Aminolevulinic Acid; Anticarcinogenic Agents; Diterpenes; Female; Fluorescence; Humans; Leukoplakia, Oral; Male; Middle Aged; Photochemotherapy; Photosensitizing Agents; Protoporphyrins; Retinyl Esters; Vitamin A