Abstract 3111: Establishment of patient-derived xenografts in penile cancer

Abstract

Abstract Background: Penile Cancer (PeCa) is a rare cancer with over 90% squamous cell carcinoma (SCC)histology. Risk factors include human papillomavirus (HPV) infection and phimosis. Molecular oncogenic pathways between HPV-Positive and HPV-Negative PeCa are difficult to validate because there are few preclinical models of PeCa and no models of HPV-Positive PeCa. Our goal was to establish PeCA patient-derived xenograft (PDX) models to elucidate the molecular signature of HPV-Positive and HPV-Negative PeCa for therapeutic benefit. Methods: PeCa specimens from penectomies and inguinal lymph node dissections (ILND) were collected from 2019-2021. Tumor specimens were dissected and tissue coated in Matrigel and transplanted subcutaneously into NOD SCID gamma (NSG™) mice. Tumor growth was monitored and was harvested at ≈ 1500m3 for subsequent propagation. Short tandem repeat fingerprinting (STR) analysis was performed on genomic DNA from PDX tissue and parental patient tumor tissue. Immunohistochemistry was performed on all PDX models and original patient primary tumors to validate the expression of p16 protein, a surrogate marker for HPV-Positive disease. p16 positivity was determined using a 0-3 scoring where a score of 3 was assessed as positive and a score of ≤2 as negative. For HPV genotyping: PCR was performed using DNA ELISA kit HPV, followed by RHA Kit HPV SPF10-LiPA25. Results: 8 PDXs were established from tissue from 7 patients. Age, race, and type of surgery were determined. SCC histology was confirmed in all the patients. Basaloid variant was present in 3 patients, and Verrucous variant was present in 1 patient. For pathological staging, 2 patients were staged as pT3N3Mx, 2 patients as pT2N1M0, 1 patient as pT3N0 and 3 patients as pT3Nx. One ILND had no evidence of disease. 2 PDX models (MDAPe3 and MDAPe7) were derived from two specimens from the same patient (1 pretreatment, 1 post-treatment). All models were matched to the patient's primary tumor by STR fingerprinting analysis. Squamous cell carcinoma histology was confirmed in all PDXs. 6 PDX models are currently in passage 3 and 6 PDXs were p16 positive. HPV genotyping in p16 positive PDXs detected high-risk HPV 16 and p16 negative xenografts were also HPV negative. Conclusion: In our study, we established PeCa PDX models that recapitulated the patients' histology. We report to our knowledge the first HPV-positive penile cancer xenografts. Plans for comprehensive characterization and future targeted therapy experiments are in development. Citation Format: Luis A. Segarra, Niki M. Zacharias, Alberto Pieretti, Angelita Alaniz, Tapati Maity, Sue Martinez, Priya Rao, Natalie Fowlkes, Jad Chahoud, Xin Lu, Magaly Martinez Ferrer, Christopher Wood, Curtis Pettaway. Establishment of patient-derived xenografts in penile cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3111.