The Correlation of Autophagy and Glycolysis Mechanism to The Histopathological Grading of Penile Squamous Cell Carcinoma Through Expression Microtubule-associated Protein 1 Light Chain 3B (LC3B) and Glucose Transporter-1 (GLUT-1) Riski Hidayat a , Jessy Chrestella b , Lidya Imelda Laksmi c Department of Anatomik Pathology. Faculty of Medicine, Universitas Sumatera Utara, Medan, Indonesia riski.pa.usu.19@gmail.com ABSTRACT Background: Penile cancer incidence is still common in developing countries. Squamous cell carcinoma (SCC) is the dominant histopathological type found in penile cancer. Autophagy and glycolysis play important roles in cancer pathology. LC3B is one of the most widely used autophagy markers and GLUT-1 is an isoform of the glucose transporter family that is expressed in many cancers. Objective: To analyze correlation of autophagy and glycolysis mechanism to the histopathological grading of penile squamous cell carcinoma through expression microtubule-associated protein1 light chain 3B (LC3B) and glucose transporter-1 (GLUT-1). Method: This study is an analysis with a cross sectional approach on 50 samples of paraffin blocks diagnosed as penile squamous cell carcinoma. All samples met the inclusion criteria and were reviewed by 2 pathologists. The results of the immunohistochemical expression of LC3B and GLUT-1 will be assessed for correlation with the histopathological grade of penile SCC. The statistical test used in this study was the Mann Whitney test. Results: A total of 50 samples of penile SCC, obtained grade I as many as 17 samples (34%), grade II 22 samples (44%), and grade III 11 samples (22%). From the results of the immunohistochemical expression of LC3B and GLUT-1 on the histopathological grading of penile SCC, the same results were found. In grade I, 15 samples were positively expressed, and 2 samples were negative. In grade II, all samples were positively expressed, and in grade III, 9 samples were positively expressed and 2 were negative. Conclusion: There was no significant correlation between the histopathological grading of penile SCC with the immunohistochemical expression of LC3B and GLUT-1 (p=0.818). Keywords: penile cancer, autophagy, glycolysis, LC3B, GLUT-1 1. Introduction Penile cancer is a rare cancer, with a prevalence of 0.1-1 per 100,000 men in high-income countries and in countries where the majority of the population is circumcised. 1,2,3 However, in less developed countries, including some countries in South America, Asia, and Africa, the incidence is very high. Brazil, Canada, and Romania are countries with the highest incidence of penile cancer in the world, with a prevalence of 6.1 per 100.00 men. 2,3 Data from the Global Burden of Cancer (GLOBOCAN) 2018 shows 34.475 new cases of penile cancer in the world and 15.138 deaths related to penile cancer. 2,4 Squamous cell carcinoma (SCC) of the penis is the predominant histopathological type of all penile cancer. 4,5 Although the pathogenesis of penile SCC remains unclear, previous studies have identified many potential risk factors, including phimosis, human papilloma virus (HPV) infection, 776 www.ijrp.org IJRP 2022, 102(1), 776-783; doi:.10.47119/IJRP1001021620223331