Expression of nectin-4 in squamous cell carcinoma of prostate: a pilot study and case report

Squamous cell carcinoma of the prostate (SCCP) is a rare subtype of prostate cancer with a poor prognosis, and no consensus exists regarding the treatment of SCCP. Nectin-4, a cell adhesion molecule predominantly expressed in a wide variety of cancers, emerged as a promising therapeutic target due to its over expression.

A 69-year-old male patient received transurethral resection of the prostate for lower urinary tract symptoms (LUTS) and was diagnosed with prostatic acinar adenocarcinoma. Androgen deprivation therapy (ADT) was administered, and 22 months later, the patient presented with LUTS again, and radical prostatectomy (RP) was performed; subsequent pathologic examination revealed mixed prostatic carcinoma, with the squamous and glandular components accounting for 70% and 30%, respectively. Immunohistochemical (IHC) staining of the mixed carcinoma tissue from the RP specimen demonstrated strong immunoreactivity for Nectin-4 exclusively in the squamous component, not the glandular component. A retrospective assay of seven additional SCCP specimens from our center showed the same result. In the current case, although apalutamide, a novel androgen receptor inhibitor, in combination with ADT and pelvic radiotherapy was administered 1 month postoperatively, the patient experienced both biochemical and radiographic progression.

This is the first report of a case of hormonal therapy-induced SCCP, in which Nectin-4 was expressed exclusively in the squamous component, not the glandular component. Nectin-4 might be a therapeutic target for SCCP.