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The prognostic significance of the aberrant extremes of p53 immunophenotypes in breast cancer
Author(s) -
Boyle David P,
McArt Darragh G,
Irwin Gareth,
WilhelmBenartzi Charlotte S,
Lioe Tong F,
Sebastian Elena,
McQuaid Stephen,
Hamilton Peter W,
James Jacqueline A,
Mullan Paul B,
Catherwood Mark A,
Harkin D Paul,
SaltoTellez Manuel
Publication year - 2014
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.12398
Subject(s) - immunohistochemistry , immunophenotyping , tissue microarray , univariate analysis , missense mutation , breast cancer , oncology , phenotype , biology , multivariate analysis , medicine , pathology , cancer research , cancer , gene , genetics , flow cytometry
Aims The utility of p53 as a prognostic assay has been elusive. The aims of this study were to describe a novel, reproducible scoring system and assess the relationship between differential p53 immunohistochemistry ( IHC ) expression patterns, TP 53 mutation status and patient outcomes in breast cancer. Methods and results Tissue microarrays were used to study p53 IHC expression patterns: expression was defined as extreme positive ( EP ), extreme negative ( EN ), and non‐extreme ( NE ; intermediate patterns). Overall survival ( OS ) was used to define patient outcome. A representative subgroup ( n = 30) showing the various p53 immunophenotypes was analysed for TP 53 hotspot mutation status (exons 4–9). Extreme expression of any type occurred in 176 of 288 (61%) cases. As compared with NE expression, EP expression was significantly associated ( P = 0.039) with poorer OS . In addition, as compared with NE expression, EN expression was associated ( P = 0.059) with poorer OS . Combining cases showing either EP or EN expression better predicted OS than either pattern alone ( P = 0.028). This combination immunophenotype was significant in univariate but not multivariate analysis. In subgroup analysis, six substitution exon mutations were detected, all corresponding to extreme IHC phenotypes. Five missense mutations corresponded to EP staining, and the nonsense mutation corresponded to EN staining. No mutations were detected in the NE group. Conclusions Patients with extreme p53 IHC expression have a worse OS than those with NE expression. Accounting for EN as well as EP expression improves the prognostic impact. Extreme expression positively correlates with nodal stage and histological grade, and negatively with hormone receptor status. Extreme expression may relate to specific mutational status.