ArticleDiagnostic pathology2025
p53 aberrant expression is pervasive in pleomorphic carcinomas of the lung and a sensitive diagnostic adjunct for biopsy specimens.
Article in Diagnostic pathology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
introductionThe prognosis of pleomorphic carcinoma of the lung is poor with a propensity of metastasis and distant recurrence. The high intratumoral heterogeneity and variable morphologic composition of pleomorphic carcinomas lead to underdiagnosis in biopsy specimens from non-small cell carcinomas. This study aims to detail the p53 expression pattern in pleomorphic carcinoma and its role in biopsy assessment.
methodsp53 immunostain was performed on a cohort of pleomorphic carcinoma resection and corresponding biopsy specimens, with TP53 sequencing performed on microdissected pleomorphic and non-pleomorphic components.
resultsA total of 30 cases were analyzed and non-pleomorphic components were identified in 11 cases. Aberrant p53 immunostain expression was seen in 24 (80%), consisting of 11 (36.7%) overexpression (≥ 90%) and 13 (43.3%) null patterns. The non-pleomorphic components showed concordant p53 expression with the pleomorphic components. All 11 corresponding biopsy specimens, and an additional adrenal metastatectomy, showed concordant aberrant p53 expression. Four cases were suitable for sequencing, and TP53 mutation was detected in all. In three cases, identical TP53 mutations (F134L, G245V and C227F) were found in the non-pleomorphic and pleomorphic components, with aberrant p53 staining. Concurrent EGFR mutation was seen in the case with C227F mutation. The remaining case showed different TP53 mutations in the non-pleomorphic (R342) and pleomorphic components (G245S with wild-typeimmunostain pattern.
conclusionTP53 mutation and aberrant p53 immunostain expression are consistently and concordantly observed in pleomorphic, non-pleomorphic components, metastatic and small biopsy specimens of pleomorphic carcinomas. There is value in performing p53 immunostain for diagnosing pleomorphic carcinoma in small specimens.
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