Oral Cancer Detection by New Concept Probe
In the treatment of oral squamous cell carcinoma (OSCC), one of the most important but difficult aspects of cancer surgery is ensuring complete removal of the tumor at the primary site. The ability of the unaided human eye to detect accurate borders between cancer and normal tissue during surgery is limited. Topical new probe: γ-glutamyl hydroxymethyl rhodamine green (γ-Glu-HMRG) reported could distinguish cancer from normal tissue in animal model. The aim of this study was to evaluate the γ-Glu-HMRG performance to distinguish oral squamous cell carcinoma (OSCC) from normal tissue.
Materials and Methods
This prospective study included 22 consecutive patients with previously untreated OSCC who were diagnosed and treated at Shinshu University School of Medicine from September, 2012 to December 2013. After radical resection of OSCC, γ-Glu-HMRG was sprayed on the surface of sliced section of OSCCs. We took fluorescent images using in vivo imager. Excitation and emission filters were 475 to 520 nm and 520 to 610 nm. Intensity of florescence was measured at representative three points (ROI; 1mm2) of either normal or carcinoma tissues in each section. Intensity of florescence was then compared between normal and carcinoma tissue in chase of time. Analysis of fluorescent intensity was performed by IndiGO software™ (BERTHOLD Japan, Tokyo).
Thereafter, the sliced section was prepared for conventional microscopic examination with hematoxylin and eosin (HE). We compared the results of fluorescence study and pathological diagnosis by two independent pathologists using the microscope system.
Methods of analysis
The fluorescent image was compared with the result of histopathological examination using a PC microscope system (NanoZoomer 2.0-HT C9600-13, Hamamatsu Photonics Co., Shizuoka, Japan)and indiGO software™.
Results
Fluorescence was firstly confirmed at invasive fronts of OSCC 1 to 3 minutes after the spraying. 25 minutes after the spraying, we could distinguish whole OSCC invasive fronts from normal tissue. In this examination with γ-Glu-HMRG, the sensitivity of the extent of the area of OSCC was clearly delineated in 19 out of 22 patients (86.4%). However, in three patients (13.6%), γ-Glu-HMRG could not detect all of OSCC tissue. The sensitivity was estimated as 86.4% (19 of 22) and the specificity 95% in OSCC patients (21 of 22). In one case, gγ-Glu-HMRG had mistaken dysplasia tissue as OSCC. Especially, invasive margin lesion had high fluorescent intensity.
Conclusions
The results of this study demonstrated that γ-Glu-HMRG could rapidly detect OSCC invasive front. Instant and complete activation of the probe makes it feasible for incorporation into surgical intraoperative resection procedures.
References
- Y. Urano, M. Sakabe, N. Kosaka, M. Ogawa, M. Mitsunaga, D. Asanuma, M. Kamiya, M. R. Young, T. Nagano, P. L. Choyke, and H. Kobayashi, “Rapid cancer detection by topically spraying a γ-glutamyltranspeptidase-activated fluorescent probe.,” Science translational medicine, vol. 3, no. 110, p. 110ra119, Nov. 2011.
- H. Kurita, T. Kamata, X. Li, Y. Nakanishi, T. Shimane, and T. Koike, “Effectiveness of vital staining with iodine solution in reducing local recurrence after resection of dysplastic or malignant oral mucosa.,” The British journal of oral & maxillofacial surgery, vol. 50, no. 2, pp. 109–12, Mar. 2012.