Correlation of TP53 Mutations With p53 Expression and Ki-67 Index in Pulmonary Large Cell Neuroendocrine Carcinomas

This study explores the locations and distribution of mutations in the exons of the TP53 gene in pulmonary large cell neuroendocrine carcinomas (LCNEC) and the corresponding expression of p53 as well as the Ki-67 proliferation index. Real-world data from routine diagnostics were collected retrospectively from 149 consecutive cases of pulmonary LCNEC. They included next-generation sequencing (NGS) of the TP53 gene along with evaluation of p53 and Ki-67 expression with immunohistochemistry (IHC). Abnormal p53 expression was defined as strong positive nuclear reaction in more than 20% of the tumor cells or complete absence of immunostaining in tumor cells. Both p53 expression and Ki-67 proliferation index correlated with TP53 mutations. In addition, a statistically significant increase in Ki-67 expression was found for cases with abnormal staining of p53 compared to samples with normal staining. We found that IHC staining for p53 can identify TP53 mutations in pulmonary LCNEC with an overall concordance of 76.6%. Moreover, both pathological patterns of p53 immunostaining and NGS-detected TP53 mutations were associated with higher Ki-67 proliferation indices.