Early Detection of Leukoplakic Oral Squamous Cell Carcinoma Using 4NQO-induced Rat Tongue Cancer Model: Study Utilizing Fluorescence Intensity and Histopathological Evaluation

Abstract

Early identification of leukoplakic oral squamous cell carcinoma (OSCC) is difficult. The purpose of this study was to determine whether it was possible to detect change from normal epithelium to leukoplakic OSCC using a fluorescence visualization (FV) device in a 4-nitroquinoline 1-oxide (4NQO) -induced rat tongue cancer model. If successful, this would facilitate early detection of OSCC. The rats (3 groups of 5) were administered 50 ppm 4NQO in their drinking water over a period of 10, 15, or 20 weeks. Five nontreated rats were used as a control group. Images of their tongues obtained by FV were analyzed for change in fluorescence intensity (FI) using image analysis software. Immunoreaction for anti-CK13, anti-CK17, and anti-E-cadherin antibodies was also histopathologically evaluated. Receiver operating characteristic (ROC) analysis was used to calculate the cut-off values, sensitivity, specificity, and area under the curve. The most marked change in FI was found between the control and 10-week groups, with an increase observed in its average value and range in the latter. These findings differed from those characteristic of leukoplakia. No significant difference was observed in the positive cell rate for immunoreaction for anti-CK13 or anti-CK17 antibodies between the control and 10-week groups. A significant decrease was observed in the positive pixel ratio of immunoreaction for anti-E-cadherin antibody in the 10-week group in comparison with in the control group (p <0.05). These results showed that disruption of intercellular adhesion could be observed at 10 weeks. In the ROC analysis, the FI cut-off value in the 10-week and control groups was 51.9, sensitivity 95.5%, and specificity 96.9%. This indicated that normal epithelium could be accurately distinguished from low-grade dysplasia with high probability. These results demonstrate that analysis of change in FI as measured by FV could facilitate early detection of leukoplakic OSCC.

Evaluation of Oral Mucosal Lesions Using the IllumiScan® Fluorescence Visualisation Device: Distinguishing Squamous Cell Carcinoma

“…Kosugi et al [ 37 ] quantitatively evaluated the changes in FI during progression in the transformation from normal epithelium to SCC in rats and reported that the FI variability increased with progression. Masuda et al reported that fluctuations in FI can distinguish normal epithelium from low-grade dysplasia [ 38 ]. Kosakai et al reported that SCC showed an uneven luminosity, while OLP showed a uniform decrease in luminosity [ 39 ].…”

Current Trends of Raman Spectroscopy in Clinic Settings: Opportunities and Challenges

“…[99] Figure 10c presents a schematic of the fabrication of functional nanotubes and a schematic of the Raman probe for detecting the oxygen content of cancer cells, where (ii) presents a comparison of the oxygen levels at different depths detected by nanoprobes in a mouse model. [100] The characteristics of SERS with fibers and NPs were incorporated into one unit in the above studies. With deep tissue penetration in SERS detection, concurrent SERS detection modalities have complementary power in pre-and intraoperative resections.…”

“…c) Schematic of the synthesis for the functional nanoprobe and the operating principle of the nanoprobe to detect oxygen levels in cancer cells. [100] Copyright 2023, John Wiley and Sons. Table 2.…”

“…[ 99 ] Figure 10c presents a schematic of the fabrication of functional nanotubes and a schematic of the Raman probe for detecting the oxygen content of cancer cells, where (ii) presents a comparison of the oxygen levels at different depths detected by nanoprobes in a mouse model. [ 100 ]…”