Department of Pathology, Hospital Clinic of Barcelona-University of Barcelona, Barcelona, Spain.
Department of Pathology, Fundació Puigvert-Universitat Autònoma de Barcelona, Barcelona, Spain.
Am J Surg Pathol. 2024 Nov 1;48(11):1439-1447. doi: 10.1097/PAS.0000000000002291. Epub 2024 Jul 23.
Penile squamous cell carcinoma (PSCC) is classified into 2 prognostically distinct types: human papillomavirus (HPV)-associated and HPV-independent. However, the impact of p53 status on prognosis remains controversial. We correlated HPV and p53 status with the prognosis of a large series of patients with PSCC. p53 was analyzed according to a recently described immunohistochemical (IHC) pattern-based framework that includes 2 normal and 4 abnormal patterns and closely correlates with TP53 mutational status. A total of 122 patients with surgically treated PSCC in 3 hospitals were included. Based on HPV in situ hybridization and p16 and p53 IHC, the tumors were classified into 3 subtypes: HPV-associated, HPV-independent/p53 normal, and HPV-independent/p53 abnormal. All patients were followed up for at least 22 months (median: 56.9 months). Thirty-six tumors (29%) were HPV-associated, 35 (29%) were HPV-independent/p53 normal, and 51 (42%) were HPV-independent/p53 abnormal. Disease-related deaths were observed in 3/36 (8%), 0/35 (0%) and 14/51 (27%) of the patients, respectively ( P < 0.001). A total of 7/14 deaths in the latter group were patients with tumors showing p53 abnormal patterns not recognized in the classic p53 IHC interpretation (basal, null, and cytoplasmic). According to our multivariate analysis, HPV-independent/p53 abnormal tumors and advanced stage were associated with impaired disease-specific survival (hazard ratio = 23.4, 95% CI = 2.7-3095.3; P = 0.001 and 16.3, 95% CI = 1.8-2151.5; P = 0.008, respectively). In conclusion, compared with patients with HPV-associated and HPV-independent/p53-normal PSCC, patients with HPV-independent/p53 abnormal PSCC have worse clinical outcomes. p53 IHC results define 2 prognostic categories in HPV-independent PSCC: HPV-independent/p53-normal tumors as low-risk tumors, whereas HPV-independent/p53-abnormal tumors as aggressive neoplasms.
阴茎鳞状细胞癌（PSCC）分为 2 种具有不同预后的类型：人乳头瘤病毒（HPV）相关和 HPV 不相关。然而，p53 状态对预后的影响仍存在争议。我们将 HPV 和 p53 状态与一系列大型 PSCC 患者的预后相关联。p53 根据最近描述的免疫组织化学（IHC）基于模式的框架进行分析，该框架包括 2 种正常和 4 种异常模式，与 TP53 突变状态密切相关。共纳入 3 家医院的 122 例接受手术治疗的 PSCC 患者。基于 HPV 原位杂交和 p16 和 p53 IHC，肿瘤分为 3 种亚型：HPV 相关、HPV 不相关/p53 正常和 HPV 不相关/p53 异常。所有患者均至少随访 22 个月（中位数：56.9 个月）。36 例（29%）肿瘤为 HPV 相关，35 例（29%）为 HPV 不相关/p53 正常，51 例（42%）为 HPV 不相关/p53 异常。36 例 HPV 相关肿瘤患者中，3 例（8%）出现疾病相关死亡，35 例 HPV 不相关/p53 正常肿瘤患者中无死亡，51 例 HPV 不相关/p53 异常肿瘤患者中 14 例（27%）死亡（P < 0.001）。在后一组中，共有 7 例死亡患者的肿瘤 p53 异常模式未被经典 p53 IHC 解释所识别（基底、空泡和细胞质）。根据我们的多变量分析，HPV 不相关/p53 异常肿瘤和晚期与疾病特异性生存受损相关（风险比=23.4，95%CI=2.7-3095.3；P=0.001 和 16.3，95%CI=1.8-2151.5；P=0.008）。总之，与 HPV 相关和 HPV 不相关/p53 正常 PSCC 患者相比，HPV 不相关/p53 异常 PSCC 患者的临床结局较差。p53 IHC 结果在 HPV 不相关的 PSCC 中定义了 2 个预后类别：HPV 不相关/p53 正常肿瘤为低风险肿瘤，而 HPV 不相关/p53 异常肿瘤为侵袭性肿瘤。
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