Anatomic pathology selected abstracts

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Correspondence: Dr. Yuxin Liu at yuxin.liu@mountsinai.org

Cytoplasmic pattern p53 immunoexpression in pelvic and endometrial carcinomas with TP53 mutation

A cytoplasmic pattern of p53 IHC expression has been reported in a rare subset of pelvic and endometrial cancers that have a TP53 mutation involving domains affecting nuclear localization. The authors conducted a study in which they reported the clinicopathologic features of 31 cases of a TP53 mutation involving nuclear localization. The large study emphasizes practical strategies for recognizing this uncommon variant and distinguishing it from the p53 wild-type pattern. It also assesses the prognostic significance of TP53 mutation involving nuclear localization in the ovarian high-grade serous carcinoma (HGSC) cohort of The Cancer Genome Atlas database. Most of the 31 tumors in the study were advanced-stage pelvic or endometrial HGSC. All TP53 mutations were predicted to result in loss of function. The p53 overexpression pattern was present in six tumors, the p53 null pattern in three, and the p53 cytoplasmic pattern in 22. The pattern predominantly consisted of weak to moderate cytoplasmic staining in more than 95 percent of tumor cells and variable intensity nuclear staining involving a range of just a few tumor cells to just under 80 percent of cells. The p53 cytoplasmic pattern was observed in all tumors with TP53 mutation in the nuclear localization domain and 33 percent to 44 percent of tumors with a mutation in the adjacent tetramerization domain or nuclear exclusion sequence (P<0.01). P16 immunoexpression was present in 74 percent of tumors. In The Cancer Genome Atlas ovarian HGSC cohort, 41 (nine percent) of 471 nonredundant TP53-mutant cases had a nuclear localization domain, tetramerization domain, or nuclear exclusion sequence mutation, but there was no significant difference in survival when compared with the cases that had TP53 mutation outside those domains (P>0.05). P53 cytoplasmic staining merits classification as an aberrant result despite coexisting nuclear staining that in some cases may resemble the p53 wild-type pattern. While positive p16 immunostaining may be of value in confirming diagnostically challenging cases of p53 cytoplasmic staining, a negative result is uninformative. Molecular testing for TP53 mutation should be considered.

Rabban JT, Garg K, Ladwig NR, et al. Cytoplasmic pattern p53 immunoexpression in pelvic and endometrial carcinomas with TP53 mutation involving nuclear localization domains: an uncommon but potential diagnostic pitfall with clinical implications. Am J Surg Pathol. 2021;45(11):1441–1451.

Correspondence: Dr. J. Rabban at joseph.rabban@ucsf.edu