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Blinded histopathological characterisation of POLE exonuclease domain ‐ mutant endometrial cancers: sheep in wolf's clothing
Author(s) -
Van Gool Inge C,
Ubachs Jef E H,
Stelloo Ellen,
Kroon Cor D,
Goeman Jelle J,
Smit Vincent T H B M,
Creutzberg Carien L,
Bosse Tjalling
Publication year - 2018
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.13338
Subject(s) - serous fluid , immunohistochemistry , mutant , endometrial cancer , wild type , biology , exonuclease , cancer , pathology , cancer research , medicine , immunology , gene , genetics , dna polymerase
Aims POLE exonuclease domain mutations identify a subset of endometrial cancer ( EC ) patients with an excellent prognosis. The use of this biomarker has been suggested to refine adjuvant treatment decisions, but the necessary sequencing is not widely performed and is relatively expensive. Therefore, we aimed to identify histopathological and immunohistochemical characteristics to aid in the detection of POLE ‐ mutant EC s. Methods and results Fifty‐one POLE ‐ mutant endometrioid, 67 POLE ‐ wild‐type endometrioid and 15 POLE ‐ wild‐type serous EC s were included (total N = 133). An expert gynaecopathologist, blinded to molecular features, evaluated each case (two or more slides) for 16 morphological characteristics. Immunohistochemistry was performed for p53, p16, MLH 1, MSH 2, MSH 6, and PMS 2. POLE ‐mutant EC s were characterised by a prominent immune infiltrate: 80% showed peritumoral lymphocytes and 59% showed tumour‐infiltrating lymphocytes, as compared with 43% and 28% of POLE ‐ wild‐type endometrioid EC s, and 27% and 13% of their serous counterparts ( P < 0.01, all comparisons). Of POLE ‐mutant EC s, 33% contained tumour giant cells; this proportion was significantly higher than that in POLE ‐wild‐type endometrioid EC s (10%; P = 0.003), but not significantly different from that in serous EC s (53%). Serous‐like features were as often (focally) present in POLE ‐mutant as in POLE ‐wild‐type endometrioid EC s (6–24%, depending on the feature). The majority of POLE ‐mutant EC s showed wild‐type p53 (86%), negative/focal p16 (82%) and normal mismatch repair protein expression (90%). Conclusions A simple combination of morphological and immunohistochemical characteristics (tumour type, grade, peritumoral lymphocytes, MLH 1, and p53 expression) can assist in prescreening for POLE exonuclease domain mutations in EC , increasing the probability of a mutation being detected from 7% to 33%. This facilitates the use of this important prognostic biomarker in routine pathology.