TP53 Mutation Status of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma with a Wild-type p53 Immunostaining Pattern

Abstract

TP53 mutation is almost invariably present in HGSC, and p53 immunostaining can be used as a surrogate marker of TP53 mutation. In cases with a wild-type p53 immunostaining pattern, direct sequencing for TP53 mutational status can be helpful to confirm the presence of a TP53 mutation.

Clinicopathological Characteristics of Well-differentiated Papillary Mesothelioma of The Peritoneum: A Single-institutional Experience of 12 Cases

“…For PAX8 and WT1 immunostaining, staining with a moderate-to-strong intensity in the nuclei was interpreted as positive expression. p53 immunostaining was interpreted as mutation pattern (all or no nuclear staining) or wild-type pattern (weak-to-moderate and patchy nuclear staining) (22)(23)(24)(25). Positive staining was considered diffuse when at least 50% of tumor cells were immunoreactive and focal when fewer than 50% of the cells were stained.…”

Targeted Sequencing of Tubo-ovarian and Peritoneal High-grade Serous Carcinoma With Wild-type p53 Immunostaining Pattern

“…A precise validation of this practice by comparison with detailed sequencing data has been limited. We recently reported the direct sequencing results of TP53 in a cohort of HGSC in parallel with p53 immunostaining results (9). In this study, next-generation sequencing (NGS) was used to confirm the data previously obtained and to investigate whether the TP53 mutational status is altered by preoperative neoadjuvant or postoperative adjuvant chemotherapy in a larger cohort of HGSC with wild-type p53 immunostaining pattern.…”

“…Systems)] according to the manufacturer's recommendations (9,(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35). Antigen retrieval was performed using Cell Conditioning Solution (CC1, Ventana Medical Systems).…”

“…Negative control was prepared by substituting non-immune serum for primary antibody, which resulted in no detectable staining. The p53 immunostaining pattern was interpreted as a missense mutation, nonsense mutation, or wild-type pattern when p53 expression was diffuse and strong (>60% of tumor cell nuclei), completely absent (0%), or focal and weakly positive, respectively (9,19,20,23).…”

“…TP53 mutations include singlebase substitutions leading to missense or non-sense point mutations, in-frame deletions or insertions, frameshift deletions or insertions, as well as mutations that affect splicing sites (5). Diffuse and strong nuclear p53 expression is regarded as indicative of a missense TP53 mutation (8,9), and the complete absence of p53 immunoreactivity results from a nonsense TP53 mutation, leading to the formation of a truncated, non-immunoreactive protein (10)(11)(12).…”