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p53 Immunohistochemistry Defines a Subset of Human Papillomavirus-Independent Penile Squamous Cell Carcinomas With Adverse Prognosis.
The American Journal of Surgical Pathology ( IF 4.5 ) Pub Date : 2024-07-23 , DOI: 10.1097/pas.0000000000002291
Isabel Trias 1 , Ferran Algaba 2 , Inés de Torres 3 , Adela Saco 1, 4 , Lorena Marimon 1, 5 , Núria Peñuelas 5 , Laia Diez-Ahijado 5 , Lia Sisuashvili 1 , Katarzyna Darecka 1 , Alba Morató 4, 5 , Marta Del Pino 4, 6 , Carla Ferrándiz-Pulido 7 , María José Ribal 8 , Tarek Ajami 8 , Juan Manuel Corral 8 , Josep Maria Gaya 9 , Oscar Reig 10, 11 , Oriol Ordi 4, 5 , Inmaculada Ribera-Cortada 1 , Adriana García-Herrera 1, 4 , Natalia Rakislova 1, 4, 5
Affiliation  

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.

中文翻译:


p53 免疫组化定义了预后不良的人瘤病毒非依赖性鳞状细胞癌的一个亚群。



鳞状细胞癌 (PSCC) 在预后上分为 2 种不同的类型:人瘤病毒 (HPV) 相关和非 HPV 依赖性。然而,p53 状态对预后的影响仍然存在争议。我们将 HPV 和 p53 状态与大量 PSCC 患者的预后相关联。根据最近描述的基于免疫组织化学 (IHC) 模式的框架分析 p53,该框架包括 2 种正常模式和 4 种异常模式,并与 TP53 突变状态密切相关。共纳入 3 家医院的 122 例手术治疗的 PSCC 患者。根据 HPV 原位杂交和 p16 和 p53 IHC,将肿瘤分为 3 个亚型:HPV 相关、HPV 非依赖性/p53 正常和 HPV 非依赖性/p53 异常。所有患者均随访至少 22 个月 (中位数: 56.9 个月)。36 例肿瘤 (29%) 与 HPV 相关,35 例 (29%) 为 HPV 非依赖性/p53 正常,51 例 (42%) 为 HPV 非依赖性/p53 异常。分别在 3/36 (8%) 、 0/35 (0%) 和 14/51 (27%) 的患者中观察到疾病相关死亡 (P< 0.001)。后一组共有 7/14 的死亡是肿瘤患者,这些肿瘤显示经典 p53 IHC 解释中未识别的 p53 异常模式 (基底、无效和细胞质)。根据我们的多变量分析,HPV 非依赖性/p53 异常肿瘤和晚期与疾病特异性生存率受损相关 (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 非依赖性/p53 正常 PSCC 患者相比,HPV 非依赖性/p53 异常 PSCC 患者的临床结局更差。 p53 IHC 结果定义了 HPV 非依赖性 PSCC 的 2 个预后类别: HPV 非依赖性/p53 正常肿瘤为低风险肿瘤,而 HPV 非依赖性/p53 异常肿瘤为侵袭性肿瘤。
更新日期:2024-07-23
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