Fluorescence Visualization Detection of Field Alterations in Tumor Margins of Oral Cancer Patients

Abstract

Purpose: Genetically altered cells could become widespread across the epithelium of patients with oral cancer, often in clinically and histologically normal tissue, and contribute to recurrent disease. Molecular approaches have begun to yield information on cancer/risk fields; tissue optics could further extend our understanding of alteration to phenotype as a result of molecular change. Experimental Design: We used a simple hand-held device in the operating room to directly visualize subclinical field changes around oral cancers, documenting alteration to fluorescence. A total of 122 oral mucosa biopsies were obtained from 20 surgical specimens with each biopsy being assessed for location, fluorescence visualization (FV) status, histology, and loss of heterozygosity (LOH; 10 markers on three regions: 3p14, 9p21, and 17p13). Results: All tumors showed FV loss (FVL). For 19 of the 20 tumors, the loss extended in at least one direction beyond the clinically visible tumor, with the extension varying from 4 to 25 mm. Thirty-two of 36 FVL biopsies showed histologic change (including 7 squamous cell carcinoma/carcinomas in situ, 10 severe dysplasias, and 15 mild/moderate dysplasias) compared with 1of the 66 FV retained (FVR) biopsies. Molecular analysis on margins with low-grade or no dysplasia showed a significant association of LOH in FVL biopsies, with LOH at 3p and/or 9p (previously associated with local tumor recurrence) present in 12 of 19 FVL biopsies compared with 3 of 13 FVR biopsies (P = 0.04). Conclusions: These data have, for the first time, shown that direct FV can identify subclinical high-risk fields with cancerous and precancerous changes in the operating room setting.

Fluorescence spectroscopy for the detection of potentially malignant disorders and squamous cell carcinoma of the oral cavity

“…The collection geometry of the spectroscopy system may also play an important role on the final collected fluorescence spectrum [24][25][26]. For oral cancer diagnostics, excitation wavelength presented as more effective is in the 400-450 nm interval [25,27]. Our results also showed that the 406 nm excitation presented more tissue information concerning malignant characteristics, even though 532 nm could potentially interrogate a deeper tissue layer.…”

“…Collagen is one of the main contributors for the oral mucosa fluorescence, and the decreased emission is related to the breakdown of the fiber links, resulted from tumor cells invasion. Neoplasia progression also involves angiogenesis, and structural epithelium changes, resulting in modification of tissue absorption and scattering [27,31,32].…”

“…Poh et al [27] using wide field fluorescence imaging showed the effectiveness of a simple handheld fluorescence system (excitation at 400-460 nm) to delineate the full extent of a tumor which, in turn, can be useful in guiding the complete tumor resection in the operating room. Optical changes, specifically the loss of fluorescence in the mucosa lesion and surrounding tissues were used to map the field cancerization.…”

“…Optical changes, specifically the loss of fluorescence in the mucosa lesion and surrounding tissues were used to map the field cancerization. Correlation of histopathological characteristics and specific genetic alterations indicate that fluorescence visualization is improved lesion delineation (size) and field cancerization detection compared to clinical judgment [16,27,32,33]. The fluorescence spectra collected in the same tissue show different ways depending on the excitation used.…”

Non-Invasive Techniques for Detection and Diagnosis of Oral Potentially Malignant Disorders

“…8-94.3 70.7-99.6 (McIntosh et al 2009;Ibrahim et al 2014) Orascoptic DK n/a n/a (Patton et al 2008) VELscope 30-100 15-100 (Poh et al 2006;Balevi 2007;Patton et al 2008;Trullenque-Eriksson et al 2009;Mehrotra et al 2010;Moro et al 2010;Awan et al 2011a;Balevi 2011;Fricain 2011;Lopez-Jornet and De la Mano-Espinosa 2011;Scheer et al 2011;Farah et al 2012;Marzouki et al 2012;Bhatia et al 2013) Photodynamic diagnosis 79-100 50-99 (Leunig et al 2000;Betz et al 2002;Zheng et al 2002;Chang and Wilder-Smith 2005;Sharwani et al 2006a;Driemel et al 2007;Sieron et al 2008) Optical diagnostic technologies…”