Expression of tissue factor (TF) in penile squamous cell carcinoma (PSCC) and enrichment in HPV-negative cases.

10 Background: Advanced/metastatic PSCC is an aggressive malignancy with limited treatment options. An antibody-drug conjugate (ADC) targeting TF is approved for treatment of advanced cervical cancer and may benefit patients with PSCC. We evaluated TF expression in PSCC which could support a future clinical trial of a TF-targeting agent for PSCC. Methods: We identified 33 pts with PSCC who underwent primary surgery at MD Anderson from 1999-2017 and had archived primary tumor tissue available for analysis. HPV-positive status was determined by either PCR testing or high-risk HPV in situ hybridization assay. A tissue microarray (TMA) was constructed with 3 cores per tumor. Anti-TF-1 antibody staining was performed by immunohistochemistry and mean H-scores for membrane and cytoplasm staining were assessed (range 0-300) for each tumor. Median H-scores were described and compared between HPV-positive and negative tumors. Percentage of pts with tumors staining positive for TF (≥10% of tumor cells with at least 1+ intensity in cytoplasm and/or membrane) was determined. Association of TF expression with tumor grade, presence of metastatic disease, lymphovascular invasion (LVI), perineural invasion (PNI), recurrence free survival (RFS), and overall survival (OS) was assessed. Results: 17 pts (51.5%) had HPV-positive disease; 19 pts (57.6%) had metastatic disease. 27 tumors (81.8%) stained positive for tissue factor. Median overall membrane TF H-score was 47 (range 1-232). HPV-negative tumors had significantly higher membrane expression of TF (median H-score 70, range 1-232) than HPV-positive tumors (median H-score 19, range 1-123; p=0.004). While analyses were limited by small sample size, we did not find a significant association of TF H-score with tumor grade, presence of metastatic disease, LVI, PNI, RFS, or OS. Conclusions: TF expression was highly prevalent in this PSCC pt cohort. HPV-negative tumors had significantly higher TF expression than HPV-positive tumors; this finding requires further study. These data support further investigation of TF-targeted therapy, such as an ADC, for treatment of PSCC. Variable Overall population HPV-positive(17 patients) HPV-negative(16 patients) Median (range) H-score Membrane 47 (1-232) 19 (1-123) 70 (1-232) Cytoplasm 29 (2-180) 18 (2-98) 59 (2-180) Positive TF expression (Percent of patients with ≥1 core having ≥10% of tumor cells with at least 1+ intensity in either cytoplasm or membrane) 27/33 (81.8%) 12/17 (70.6%) 15/16 (93.8%)