Case report: squamous cell carcinoma of the prostate-a clinicopathological and genomic sequencing-based investigation

Squamous differentiation of prostate cancer, which accounts for less than 1% of all cases, is typically associated with androgen deprivation treatment (ADT) or radiotherapy. This entity is aggressive and exhibits poor prognosis due to limited response to traditional treatment. However, the underlying molecular mechanisms and etiology are not fully understood. Previous findings suggest that squamous cell differentiation may potentially evolve from prostate adenocarcinoma (AC), as four cases of squamous cell carcinoma (SCC) of the prostate were detected with ERG pathway activation, but further validation is needed to confirm this hypothesis. This paper presents a case of advanced prostate cancer with a combined histologic pattern, including keratinizing SCC and AC. The study utilized whole-exome sequencing (WES) data to analyze both subtypes and identified significant genetic overlap between the two, despite having a non-ERG activation molecular signature. This discovery supports previous research that suggests squamous differentiation develops from prostate adenocarcinoma. Moreover, the transformation to squamous cell carcinoma in the prostate may involve various molecular pathways such as the reactivation of the AR pathway, genome instability, and abnormal R-loop formation. This indicates the need for individualized clinical management of prostate SCC, and specific molecular findings may aid in optimizing treatment strategies.前列腺癌鳞状分化占所有前列腺癌病例的比例不足1%，通常与雄激素剥夺治疗（androgen deprivation treatment, ADT）或放射治疗相关。该亚型侵袭性较强，且因对传统治疗响应有限而预后不良。然而，其潜在分子机制与病因尚未完全阐明。既往研究提示，鳞状细胞分化可能由前列腺腺癌（prostate adenocarcinoma, AC）演化而来：曾有4例前列腺鳞状细胞癌（squamous cell carcinoma, SCC）病例被检出存在ERG通路（ERG pathway）激活，但该假说仍需进一步验证。本文报道1例兼具角化型鳞状细胞癌与腺癌组织学特征的晚期前列腺癌病例。本研究利用全外显子组测序（whole-exome sequencing, WES）数据对两种亚型进行分析，尽管二者均未呈现ERG激活的分子特征，但鉴定出二者存在显著的遗传重叠。这一发现支持了此前关于前列腺鳞状分化起源于前列腺腺癌的研究结论。此外，前列腺组织向鳞状细胞癌的转化可能涉及多种分子通路，如AR通路（AR pathway）再激活、基因组不稳定以及异常R环（R-loop）形成。这提示临床需对前列腺鳞状细胞癌实施个体化管理，相关特异性分子特征可为优化治疗策略提供参考。