Hostname: page-component-78c5997874-v9fdk Total loading time: 0 Render date: 2024-11-13T01:46:41.155Z Has data issue: false hasContentIssue false

Epithelial Distribution of E-Cadherin, p63, and Mitotic Figures in ApoTome Images to Determine the Oncogenic Potentiality of Oral Submucous Fibrosis

Published online by Cambridge University Press:  14 October 2020

Reetoja Nag*
Affiliation:
Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology, Room No. 402, ALM Building, Vellore 632014, Tamil Nadu, India
Ranjan Rashmi Paul
Affiliation:
Gurunanak Institute of Dental Sciences and Research, Panihati 700114, West Bengal, India
Mousumi Pal
Affiliation:
Gurunanak Institute of Dental Sciences and Research, Panihati 700114, West Bengal, India
Jyotirmoy Chatterjee
Affiliation:
School of Medical Science and Technology, Indian Institute of Technology, Kharagpur 721302, West Bengal, India
Raunak Kumar Das*
Affiliation:
Centre for Biomaterials, Cellular and Molecular Theranostics, Vellore Institute of Technology, Room No. 402, ALM Building, Vellore 632014, Tamil Nadu, India
*
*Author for correspondence: Reetoja Nag, E-mail: nagreetoja@gmail.com; and Raunak Kumar Das E-mail: raunakkumardas@vit.ac.in
*Author for correspondence: Reetoja Nag, E-mail: nagreetoja@gmail.com; and Raunak Kumar Das E-mail: raunakkumardas@vit.ac.in
Get access

Abstract

The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.

Type
Biological Applications
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Angadi, PV & Rao, SS (2011). Areca nut in pathogenesis of oral submucous fibrosis: Revisited. Oral Maxillofac Surg 15(1), 19. doi:10.1007/s10006-010-0219-8CrossRefGoogle ScholarPubMed
Angadi, PV, Savitha, JK, Rao, SS & Sivaranjini, Y (2012). Oral field cancerization: Current evidence and future perspectives. Oral Maxillofac Surg 16(2), 171180. doi:10.1007/s10006-012-0317-xCrossRefGoogle ScholarPubMed
Ankle, MR, Kale, AD & Charantimath, S (2007). Comparison of staining of mitotic figures by haematoxylin and eosin-and crystal violet stains, in oral epithelial dysplasia and squamous cell carcinoma. Indian J Dent Res 18(3), 101.CrossRefGoogle ScholarPubMed
Argiris, A, Karamouzis, MV, Raben, D & Ferris, RL (2008). Head and neck cancer. Lancet 371(9625), 16951709. doi:10.1016/S0140-6736(08)60728-XCrossRefGoogle ScholarPubMed
Carico, E, Atlante, M, Giarnieri, E, Raffa, S, Bucci, B, Giovagnoli, MR & Vecchione, A (2010). E-cadherin and alpha-catenin expression in normal, hyperplastic and neoplastic endometrium. Anticancer Res 30(12), 49934997.Google ScholarPubMed
Chang, YC, Nieh, S, Chen, SF, Jao, SW, Lin, YL & Fu, E (2010). Invasive pattern grading score designed as an independent prognostic indicator in oral squamous cell carcinoma. Histopathology 57(2), 295303. doi:10.1111/j.1365-2559.2010.03616.xCrossRefGoogle ScholarPubMed
Chaw, SY, Majeed, AA, Dalley, AJ, Chan, A, Stein, S & Farah, CS (2012). Epithelial to mesenchymal transition (EMT) biomarkers—E-cadherin, beta-catenin, APC and vimentin—in oral squamous cell carcinogenesis and transformation. Oral Oncol 48(10), 9971006. doi:10.1016/j.oraloncology.2012.05.011CrossRefGoogle ScholarPubMed
Choi, S & Myers, JN (2008). Molecular pathogenesis of oral squamous cell carcinoma: Implications for therapy. J Dent Res 87(1), 1432. doi:10.1177/154405910808700104CrossRefGoogle ScholarPubMed
Dagli, RJ, Kumar, S, Mathur, A, Balasubrimanyam, G, Duraiswamy, P & Kulkarni, S (2008). Prevalence of leukoplakia, oral submucous fibrosis, papilloma and its relation with stress among green marbles mine laborers, India. Med Oral Patol Oral Cir Bucal 13(11), E687E692.Google ScholarPubMed
Das, RK, Pal, M, Barui, A, Paul, RR, Chakraborty, C, Ray, AK & Chatterjee, J (2012). ApoTome to visualize E-cadherin and p63 expression in oral pre-cancer. Biotechnol J 7(5), 602607. doi:10.1002/biot.201100013CrossRefGoogle ScholarPubMed
Das, RK, Pal, M, Barui, A, Paul, RR, Chakraborty, C, Ray, AK, Sengupta, S & Chatterjee, J (2010 a). Assessment of malignant potential of oral submucous fibrosis through evaluation of p63, E-cadherin and CD105 expression. J Clin Pathol 63(10), 894899. doi:10.1136/jcp.2010.078964CrossRefGoogle ScholarPubMed
Das, RK, Venkatraghavan, V, Sheet, D, Chakraborty, C, Ray, AK, Chatterjee, J, Pal, M & Paul, RR (2010 b). Evaluation of p63 expression in oral sub-mucous fibrosis. In 2010 International Conference on Systems in Medicine and Biology, pp. 166–171. IEEE. doi:10.1109/ICSMB.2010.5735365CrossRefGoogle Scholar
De Matos, LL, Trufelli, DC, De Matos, MGL & da Silva Pinhal, MA (2010). Immunohistochemistry as an important tool in biomarkers detection and clinical practice. Biomark Insights 5. doi:10.4137/BMI.S2185CrossRefGoogle Scholar
Ferlay, J, Shin, HR, Bray, F, Forman, D, Mathers, C & Parkin, DM (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12), 28932917. doi:10.1002/ijc.25516CrossRefGoogle ScholarPubMed
Garmel, GM (2004). Dorland's Illustrated Medical Dictionary: Philadelphia, PA: WB Saunders (an imprint of Elsevier), 2003, 2,190 pages, $49.95 (hardcover). Acad Emerg Med 11(4), 410.CrossRefGoogle Scholar
Ghaznavi, F, Evans, A, Madabhushi, A & Feldman, M (2013). Digital imaging in pathology: Whole-slide imaging and beyond. Annu Rev Pathol: Mech Dis 8, 331359. doi:10.1146/annurev-pathol-011811-120902CrossRefGoogle ScholarPubMed
Gustafsson, MG, Shao, L, Carlton, PM, Wang, CR, Golubovskaya, IN, Cande, WZ, Agard, DA & Sedat, JW (2008). Three-dimensional resolution doubling in wide-field fluorescence microscopy by structured illumination. Biophys J 94(12), 49574970. doi:10.1529/biophysj.107.120345CrossRefGoogle ScholarPubMed
Haris, PS, Balan, A, Jayasree, RS & Gupta, AK (2009). Autofluorescence spectroscopy for the in vivo evaluation of oral submucous fibrosis. Photomed Laser Surg 27(5), 757761. doi:10.1089/pho.2008.2355CrossRefGoogle ScholarPubMed
Irshad, H (2013). Automated mitosis detection in histopathology using morphological and multi-channel statistics features. J Pathol Inf 4. doi:10.4103/2153-3539.112695.Google ScholarPubMed
Irshad, H, Jalali, S, Roux, L, Racoceanu, D, Hwee, LJ, Le Naour, G & Capron, F (2013). Automated mitosis detection using texture, SIFT features and HMAX biologically inspired approach. J Pathol Inf 4 (Suppl). doi:10.4103/2153-3539.109870Google ScholarPubMed
Jeanes, A, Gottardi, CJ & Yap, AS (2008). Cadherins and cancer: How does cadherin dysfunction promote tumor progression? Oncogene 27(55), 6920.CrossRefGoogle ScholarPubMed
Karadaglić, D & Wilson, T (2008). Image formation in structured illumination wide-field fluorescence microscopy. Micron 39(7), 808818. doi:10.1016/j.micron.2008.01.017CrossRefGoogle ScholarPubMed
Kaur, G, Carnelio, S, Rao, N & Rao, L (2009). Expression of E-cadherin in primary oral squamous cell carcinoma and metastatic lymph nodes: An immunohistochemical study. Indian J Dent Res 20(1), 71.Google ScholarPubMed
Landini, G (2006). Quantitative analysis of the epithelial lining architecture in radicular cysts and odontogenic keratocysts. Head Face Med 2(1), 4. doi:10.1186/1746-160X-2-4CrossRefGoogle ScholarPubMed
Langhorst, MF, Schaffer, J & Goetze, B (2009). Structure brings clarity: Structured illumination microscopy in cell biology. Biotechnol J 4(6), 858865. doi:10.1002/biot.200900025CrossRefGoogle ScholarPubMed
Mehanna, HM, Rattay, T, Smith, J & McConkey, CC (2009). Treatment and follow-up of oral dysplasia—a systematic review and meta-analysis. Head Neck 31(12), 16001609. doi:10.1002/hed.21131CrossRefGoogle ScholarPubMed
Mestre, T, Figueiredo, J, Ribeiro, AS, Paredes, J, Seruca, R & Sanches, JM (2016). Quantification of topological features in cell meshes to explore E-cadherin dysfunction. Sci Rep 6, 25101. doi:10.1038/srep25101CrossRefGoogle ScholarPubMed
Molinolo, AA, Amornphimoltham, P, Squarize, CH, Castilho, RM, Patel, V & Gutkind, JS (2009). Dysregulated molecular networks in head and neck carcinogenesis. Oral Oncol 45(4–5), 324334. doi:10.1016/j.oraloncology.2008.07.011CrossRefGoogle ScholarPubMed
Motiwale, G, Jaiswal, S, Vikey, A, Motiwale, T, Bagulkar, B, Bhat, A & Kapoor, P (2016). Evaluation of efficacy of 1% Crystal Violet & Nuclear Fast Red stain compared to Haematoxyline & Eosin stain for assessing mitotic figures in oral premalignant and malignant lesions. Journal of experimental therapeutics & oncology 11(3), 165170.Google Scholar
Napier, SS & Speight, PM (2008). Natural history of potentially malignant oral lesions and conditions: An overview of the literature. J Oral Pathol Med 37(1), 110. doi:10.1111/j.1600-0714.2007.00579.xCrossRefGoogle ScholarPubMed
Onder, TT, Gupta, PB, Mani, SA, Yang, J, Lander, ES & Weinberg, RA (2008). Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways. Cancer Res 68(10), 36453654. doi:10.1158/0008-5472.CAN-07-2938CrossRefGoogle ScholarPubMed
Pal, M, Chaudhuri, SR, Jadav, A, Banerjee, S, Paul, RR, Dutta, PK, Ghosh, B, Chatterjee, J & Chaudhuri, K (2008). Quantitative dimensions of histopathological attributes and status of GSTM1–GSTT1 in oral submucous fibrosis. Tissue Cell 40(6), 425435. doi:10.1016/j.tice.2008.04.003CrossRefGoogle ScholarPubMed
Petersen, PE (2009). Oral cancer prevention and control—The approach of the World Health Organization. Oral Oncol 45(4–5), 454460. doi:10.1016/j.oraloncology.2008.05.02CrossRefGoogle ScholarPubMed
Rastogi, T, Devesa, S, Mangtani, P, Mathew, A, Cooper, N, Kao, R & Sinha, R (2007). Cancer incidence rates among south asians in four geographic regions: India, Singapore, UK and US. Int J Epidemiol 37(1), 147160. doi:10.1093/ije/dym219CrossRefGoogle ScholarPubMed
Regezi, JA, Sciubba, J & Jordan, RC (2016). Oral Pathology: Clinical Pathologic Correlations. USA: Elsevier Health Sciences.Google Scholar
Schmalhofer, O, Brabletz, S & Brabletz, T (2009). E-cadherin, β-catenin, and ZEB1 in malignant progression of cancer. Cancer Metastasis Rev 28(1–2), 151166. doi:10.1007/s10555-008-9179-yCrossRefGoogle ScholarPubMed
Scully, C & Bagan, J (2009). Oral squamous cell carcinoma overview. Oral Oncol 45(4/5), 301308. doi:10.1016/j.oraloncology.2009.01.004CrossRefGoogle Scholar
Shaheen, NJ, Sharma, P, Overholt, BF, Wolfsen, HC, Sampliner, RE, Wang, KK, Galanko, JA, Bronner, MP, Goldblum, JR, Bennett, AE & Jobe, BA (2009). Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med 360(22), 22772288. doi:10.1056/NEJMoa0808145CrossRefGoogle ScholarPubMed
Sinha, A, Chandra, S, Raj, V, Zaidi, I, Saxena, S & Dwivedi, R (2015). Expression of p63 in potentially malignant and malignant oral lesions. J Oral Biol Craniofacial Res 5(3), 165172. doi:10.1016/j.jobcr.2015.07.001CrossRefGoogle ScholarPubMed
Torre, LA, Bray, F, Siegel, RL, Ferlay, J, Lortet-Tieulent, J & Jemal, A (2015). Global cancer statistics, 2012. CA Cancer J Clin 65(2), 87108. doi:10.3322/caac.21262CrossRefGoogle ScholarPubMed
Uhlmann, V, Delgado-Gonzalo, R, Unser, M, Michel, PO, Baldi, L & Wurm, FM (2016). User-friendly image-based segmentation and analysis of chromosomes. In 2016 IEEE 13th International Symposium on Biomedical Imaging (ISBI), pp. 395–398. IEEE. doi:10.1109/ISBI.2016.7493291CrossRefGoogle Scholar
Van der Waal, I (2009). Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. Oral Oncol 45(4–5), 317323. doi:10.1016/j.oraloncology.2008.05.016CrossRefGoogle ScholarPubMed
Van Roy, F & Berx, G (2008). The cell-cell adhesion molecule E-cadherin. Cell Mol Life Sci 65(23), 37563788. doi:10.1007/s00018-008-8281-1CrossRefGoogle ScholarPubMed
Varun, BR, Ranganathan, K, Rao, UK & Joshua, E (2014). Immunohistochemical detection of p53 and p63 in oral squamous cell carcinoma, oral leukoplakia, and oral submucous fibrosis. J Investig Clin Dent 5(3), 214219. doi:10.1111/jicd.12038CrossRefGoogle ScholarPubMed
Veta, M, Pluim, JP, Van Diest, PJ & Viergever, MA (2014). Breast cancer histopathology image analysis: A review. IEEE Trans Biomed Eng 61(5), 14001411. doi:10.1109/TBME.2014.2303852CrossRefGoogle ScholarPubMed
Veta, M, Van Diest, PJ, Willems, SM, Wang, H, Madabhushi, A, Cruz-Roa, A, Gonzalez, F, Larsen, AB, Vestergaard, JS, Dahl, AB & Cireşan, DC (2015). Assessment of algorithms for mitosis detection in breast cancer histopathology images. Med Image Anal 20(1), 237248. doi:10.1016/j.media.2014.11.010CrossRefGoogle ScholarPubMed
Vigneswaran, N & Williams, MD (2014). Epidemiologic trends in head and neck cancer and aids in diagnosis. Oral Maxillofac Surg Clin 26(2), 123141. doi:10.1016/j.coms.2014.01.001CrossRefGoogle ScholarPubMed
Warnakulasuriya, S (2009). Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45(4–5), 309316. doi:10.1016/j.oraloncology.2008.06.002CrossRefGoogle ScholarPubMed
Xavier, FCA, Takiya, CM, Reis, SRA & Ramalho, LMP (2009). P63 immunoexpression in lip carcinogenesis. J Mol Histol 40(2), 131137. doi:10.1007/s10735-009-9223-4CrossRefGoogle ScholarPubMed
Supplementary material: File

Nag et al. supplementary material

Nag et al. supplementary material

Download Nag et al. supplementary material(File)
File 11.1 KB