Nucl Med Mol Imaging.  2025 Apr;59(2):135-146. 10.1007/s13139-024-00877-y.

Assessing ¹⁸F‑FDG PET/CT Uptake and its Correlation with Molecular Biomarkers in Penile Cancer

• Salazar A
• Júnior E
• Sánchez D
• Gonçalves A
• Simões R
• Silva‑Filho R
• Raimundo J
• Soares Y
• Marinho M
• Cubilla A
• Mamede M

• KMID: 2567346
• DOI: http://doi.org/10.1007/s13139-024-00877-y

Abstract

Background
Penile Cancer is a rare and aggressive disease. Related to complex metabolic processes.
Objective
This study investigates the effectiveness ­of ¹⁸F-FDG PET/CT as a noninvasive method in evaluating penile cancer patients, focusing on the correlation between tissue expression of key tumor markers involved in glucose metabolism and proliferation, and the uptake of ¹⁸F-FDG.
Methods
Fifty-one patients were selected and underwent ¹⁸F-FDG PET/CT-based staging. Semiquantitative analysis was performed using the maximum standardized uptake value ­(SUV_max ) and volumetric SUV ­(SUV_2SD ). Tissue expression analysis of GLUT-1, hexokinase-II, Ki67, p16, and p53 was performed by tissue microarray. PCR evaluated HPV DNA.
Results
Warty SCC showed the highest SUV value and significant differences in ­SUV_max (p=0.015). Higher ­SUV_max and SUV_2SD 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 significantly differed 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
The study highlights correlations between the uptake of ¹⁸F-FDG and the expression of markers associated with glycolytic metabolism in penile cancer. It suggests a potential trend where increased expression of glucose transport markers is linked to higher histological grades and Ki-67 expression. There were no significant differences regarding HPV positivity, demonstrating the complexity of penile cancer molecular biology and need more studies with a higher number of patients.

Keyword

Penile Neoplasm; ¹⁸F-FDG; GLUT-1; HK-II; HPV; Proliferation biomarkers