Diagnostic accuracy of p53 immunohistochemistry as surrogate of TP53 sequencing in endometrial cancer

Aberrant p53 immunohistochemical expression is used to identify the copy-number-high/TP53-mutant subgroup of endometrial cancer (EC). We aimed to determine the diagnostic accuracy of p53 immunohistochemistry as surrogate for TP53 sequencing through a systematic review and meta-analysis. Electronic databases were searched from their inception to June 2019. All studies assessing p53 expression and TP53 mutations in EC were included. Diagnostic accuracy was assessed based on area under the curve (AUC). Immunohistochemical criteria used to define aberrant p53 expression were “overexpression” and “overexpression or complete absence”. Subgroup analysis was based on the sequencing technique adopted (Polymerase Chain Reaction + sequencing, or next generation sequencing, NGS). Thirteen observational studies with 727 endometrial cancers were included. Both “overexpression” and “overexpression or complete absence” showed high diagnostic accuracy (AUC = 0.9088 and 0.9030, respectively). The subgroup with “overexpression” and NGS showed the best results, with very high diagnostic accuracy (AUC = 0.9927). In conclusion, immunohistochemistry for p53 is a highly accurate surrogate of TP53 sequencing. Overexpression of p53 in ≥70−80% showed the best accuracy in predicting TP53 mutations. Further studies in this field should adopt optimized immunohistochemical procedures and take into account less common p53 patterns (e.g. cytoplasmic expression)