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Is p53 Immunohistochemistry a Reliable Indicator of TP53 mutation? An NGS-based assessment in lung adenocarcinoma
Gizem Teoman1, Zeynep Sagnak Yilmaz2, Safak Ersoz3
1Gizem Teoman, MD Assistant Professor, Department of Medical Pathology, Karadeniz Technical University, Faculty of Medicine, Trabzon, Turkey.
Objective:
To evaluate the concordance between p53 immunohistochemistry (IHC) patterns and TP53 mutation types identified by next-generation sequencing (NGS) in lung adenocarcinoma.
Methodology:
In this retrospective study, 166 lung adenocarcinoma cases diagnosed between 2020 and 2025 at the Department of Medical Pathology, Karadeniz Technical University Faculty of Medicine were analyzed. p53 IHC staining was classified as overexpression, null, or wild-type. TP53 mutations detected by NGS were categorized as missense, nonsense, frameshift, or splice-site variants. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each IHC pattern for predicting its corresponding mutation class were calculated using NGS as the reference standard.
Results:
p53 IHC showed overexpression in one hundred eighteen cases (71.1%), a null pattern in forty-two (25.3%), and wild-type staining in six (3.6%). TP53 mutations included missense (74.1%), nonsense (11.4%), frameshift (10.2%), and splice-site variants (4.3%). Overexpression strongly correlated with missense mutations: 117 of 118 overexpression cases (99.2%) carried missense variants. The null pattern was mainly associated with truncating mutations, including nonsense and frameshift variants. Wild-type staining showed heterogeneous profiles. Overexpression predicted missense mutations with a sensitivity of 95.1%, specificity of 97.7%, PPV of 99.2%, and NPV of 87.5%. The null pattern predicted nonsense mutations with moderate PPV but high NPV.
Conclusions:
p53 IHC is a reliable surrogate marker for identifying TP53 missense mutations in lung adenocarcinoma, with overexpression demonstrating excellent diagnostic accuracy. Although the null pattern has limited PPV for nonsense mutations, its high NPV supports its use in excluding such variants. p53 IHC may serve as a practical and cost-effective approach for inferring TP53 mutation status, particularly in settings where molecular testing is restricted.
