Institute of Pathology, Charité Berlin, Berlin, Germany.
Department of Urology, Charité Berlin, Berlin, Germany.
Acta Oncol. 2023 Dec;62(12):1880-1889. doi: 10.1080/0284186X.2023.2277344. Epub 2023 Nov 25.
Most inactivating p53 mutations result in a nuclear p53 accumulation - detectable by immunohistochemistry (IHC). p53 alterations leading to a complete lack of p53 protein and absence of immunostaining do also occur - not easily detectable by IHC. p16 is upregulated in p53 inactivated cells. We hypothesized that a positive p16 IHC may help to distinguish p53 inactivation in IHC negative cases.
We investigated p53 and p16 immunostaining on 2710 urothelial bladder carcinomas in a tissue microarray format to understand their impact in relation to clinicopathological parameters of disease progression and patient outcome.
p16 immunostaining was absent in normal urothelium but occurred in 63.5% (30.4% strong) of cancers. p16 strongly positive cases increased from pTaG2 low-grade (9.6%) to pTaG3 high-grade tumors (46.5%, < .0001) but decreased from pTaG3 to pT4 (33.3%; = .0030). Among pT2-4 carcinomas, p16 positivity was linked to high-grade ( = .0005) but unrelated to overall survival. p53 staining was negative in 8.4%, very weak in 15.4%, weak in 55.3%, strong in 4.7%, and very strong in 16.2% cancers. p53 negative (potentially p53 null phenotype), strong, and very strong p53 positivity increased from pTaG2 low-grade to pTaG3 high-grade tumors ( < .0001) and from pTaG3 to pT2-4 cancers ( = .0007). p53 staining was largely unrelated to histopathological parameters or patient prognosis among pT2-4 carcinomas, except of p53 strong/very strong immunostaining. p16 expression predominated in tumors with very strong, strong, and negative p53 staining and the combination of p53 negative/p16 strongly positive cancers was linked to features of tumor aggressiveness.
Aberrant p53 and p16 immunostaining increases during grade and stage progression although p53 negative and p16 positive immunostaining lack prognostic significance in pT2-4 carcinomas. Potential diagnostic features are that high level p16 expression is limited to neoplastic urothelium and p53 null phenotype to aggressive cancers (grade 3 and invasive).
大多数失活的 p53 突变导致核 p53 积累 - 可通过免疫组织化学（IHC）检测到。也会发生导致完全缺乏 p53 蛋白和免疫染色缺失的 p53 改变 - 这些改变不易通过 IHC 检测到。p16 在 p53 失活的细胞中上调。我们假设阳性 p16 IHC 可能有助于区分 IHC 阴性病例中的 p53 失活。
我们在组织微阵列中研究了 2710 例尿路上皮膀胱癌中的 p53 和 p16 免疫染色，以了解它们与疾病进展和患者预后的临床病理参数的关系。
p16 免疫染色在正常尿路上皮中缺失，但在 63.5%（30.4%强）的癌症中发生。p16 强阳性病例从 pTaG2 低级别（9.6%）增加到 pTaG3 高级别肿瘤（46.5%，<0.0001），但从 pTaG3 减少到 pT4（33.3%；=0.0030）。在 pT2-4 癌中，p16 阳性与高级别相关（=0.0005），但与总生存率无关。p53 染色阴性（潜在的 p53 缺失表型）、弱阳性、弱阳性、强阳性和极强阳性的 p53 阳性率从 pTaG2 低级别增加到 pTaG3 高级别肿瘤（<0.0001），从 pTaG3 增加到 pT2-4 癌（=0.0007）。p53 染色在 pT2-4 癌中与组织病理学参数或患者预后基本无关，除了 p53 强/极强免疫染色外。p16 表达在极强、强和阴性 p53 染色的肿瘤中占主导地位，p53 阴性/p16 强阳性癌症的组合与肿瘤侵袭性特征相关。
尽管 p53 阴性和 p16 阳性免疫染色在 pT2-4 癌中缺乏预后意义，但 p53 和 p16 免疫染色在分级和分期进展过程中增加。潜在的诊断特征是高水平的 p16 表达仅限于肿瘤性尿路上皮，而 p53 缺失表型仅限于侵袭性癌症（3 级和浸润性）。
