P53 in Penile Squamous Cell Carcinoma: A Pattern-Based Immunohistochemical Framework with Molecular Correlation

Area of Science:

• Oncology
• Molecular Pathology
• Genitourinary Pathology

Background:

• p53 immunohistochemistry (IHC) is explored as a surrogate marker for TP53 mutations in penile squamous cell carcinomas (PSCC).
• Accurate detection of TP53 mutational status is crucial for understanding PSCC pathogenesis and guiding treatment.
• Current p53 IHC interpretation methods may lack sufficient sensitivity and accuracy for reliable TP53 mutation surrogate detection.

Purpose of the Study:

• To evaluate the performance of a novel pattern-based framework for p53 IHC in PSCC.
• To compare the diagnostic accuracy of pattern-based p53 IHC with conventional interpretation against TP53 mutational status.
• To determine if pattern-based p53 IHC can serve as a more reliable surrogate for TP53 mutations in PSCC.

Main Methods:

• A series of 40 penile squamous cell carcinoma (PSCC) cases were analyzed.
• Human papillomavirus (HPV) DNA testing, p16, and p53 IHC were performed.
• Whole exome sequencing was used to determine TP53 mutational status.
• p53 IHC was interpreted using both a pattern-based framework and conventional methods.

Main Results:

• The study included 40 PSCC cases, with 12 (30.0%) HPV-associated and 28 (70.0%) HPV-independent.
• Pattern-based p53 IHC showed almost perfect agreement (k = 0.85) with TP53 mutational status.
• The pattern-based framework achieved 95.5% sensitivity and 92.5% accuracy, significantly outperforming conventional p53 IHC (54.5% sensitivity, 70.0% accuracy).
• Specificities were comparable between the two p53 IHC interpretation methods (88.9%).

Conclusions:

• The pattern-based framework for p53 IHC interpretation substantially enhances the accuracy of detecting TP53 mutations in PSCC.
• This refined IHC approach offers a more reliable and accurate method for assessing TP53 status in penile cancer compared to traditional interpretation.
• Pattern-based p53 IHC holds promise as a valuable diagnostic tool in the management of penile squamous cell carcinomas.