Detection of GLUT-1, Hexokinase-Ii, Ki-67, P53, and P16 Levels and HPV With 18F-Fdg PET/CT in Penile Cancer

Abstract

Abstract Introduction: Penile cancer (PC) is a rare tumor. It is associated with chronic inflammation and human papilloma virus (HPV) infection. Recent results of 18F-FDG PET/CT studies have demonstrated the great potential of 18F-FDG PET/CT as a noninvasive tool for assessing PC patients. Cancer cells overexpress transmembrane glucose transporters (GLUTs) and hexokinase (HK) during times of high glucose metabolism. Ki-67 is a nuclear protein linked to DNA replication. In PC, the HPV virus has oncoproteins that can interfere with the activities of the p16 and p53 tumor suppressor proteins associated with DNA replication, leading to changes related to PC carcinogenesis. Purpose: Determine the correlation of the immunohistochemistry positivity of tumor molecular markers related to glucose metabolism, proliferation, and HPV with 18F-FDG uptake in penile cancer. Procedures: Fifty-one patients were selected and underwent 18F-FDG PET/CT-based staging. Semiquantitative analysis was performed using the maximum standardized uptake value (SUVmax) and volumetric SUV (SUV2SD). HPV DNA was extracted and identified. Three pathologists performed immunohistochemistry analysis with anti-GLUT-1, anti-hexokinase-II, anti-Ki67, anti-p16, and anti-p53 antibodies. Results: Of the 51 analyzed patients, 80.6% had invasive usual squamous cell carcinoma (SCC), and 42 patients were HPV+ (52.4%). Warty SCC showed the highest SUV value, and there were significant differences in SUVmax (p=0.015). Higher SUVmax and SUV2SD values were observed in grade 3 tumors. In typical invasive SCC, grade 3, HPV+, p16-negative, p53-negative, GLUT-1 i-3, and HK-II i-3 tumors showed a higher mean SUV. The Ki-67 value was significantly different for grade 3 tumors (p=0.001) and HK-II i-1 tumors (p=0.036). Ki-67 positivity was also higher in HPV-, p16 i-2, p53 i-3, and GLUT-1 i-3 tumors; none of the differences were statistically significant. Conclusions: In PC, high uptake of 18F-FDG correlated with higher expression of glycolytic metabolism markers. There was a trend for positive correlation between increased expression of glucose transport markers and higher histological grade and higher Ki-67 expression. HPV-negative patients showed more significant relationships between PET/CT results and markers of proliferation.