Meeting abstract from 17th Biennial Meeting of the International Gynecologic Cancer Society Kyoto, Japan September 14-16, 201

Bosse, T

Brenton, J

Gilks, CB

Jeyarajah, A

Jimenez-Linan, M

Kobel, M

Manchanda, R

Piskorz, A

Singh, N

International Journal of Gynecological Cancer

English

Queen Mary Research Online

P53 IMMUNOHISTOCHEMISTRY AS A SURROGATE FOR TP53 MUTATIONAL ANALYSIS IN ENDOMETRIAL CANCER BIOPSIES  Naveena Singh1, Anna Piskorz2, Tjalling Bosse3, Mercedes Jimenez-Linan4, Arjun Jeyarajah1, Ranjit Manchanda1, C Blake Gilks6, James Brenton2, Martin Köbel7  1Barts Health NHS Trust, London, UK; 2University of Cambridge, Cambrige, UK; 3University of Leiden, Leiden, The Netherlands; 4Addenbrooke’s Hospital, Cambridge, UK; 5Vancouver General Hospital, Vancouver, British Columbia, Canada; 6University of Calgary, Calgary, Alberta, Canada   Background and Aims p53 immunohistochemistry (IHC) has high specificity for TP53 mutation in ovarian carcinoma. Four molecular subtypes of endometrial carcinoma (EC) have been identified; accuracy of p53 IHC as a surrogate for TP53 mutation and thereby for serous-like EC is not established. We aimed to test whether p53 IHC predicts TP53 mutation in EC biopsies, universally and/or as part of a molecular classification algorithm and to compare interpretation results of p53 IHC between laboratories.  Methods 200 EC biopsies were selected from 5 histopathology laboratories to include serous:non-serous high grade:G1-2 endometrioid EC in a 2:1:1 ratio. Local p53 IHC results were compared to central reference results. Central p53 IHC results were compared to tagged-amplicon NGS TP53 sequencing results.   Results  There was 95% complete concordance between local and central p53 IHC results. On preliminary results, deleterious TP53 mutations were detected in 104/170 cases (excluding cases with failed analysis (n=23) and those showing heterogeneous p53 IHC (n=7)). Correlation between TP53 mutation and p53 IHC (Table 3) shows 91% accuracy (sensitivity 90.4%; specificity 91.2%). Correlation between TP53 mutation and p53 IHC as part of an algorithm, ie after exclusion of mismatch repair defective and DNA polymerase epsilon exonuclease domain (POLE) mutant cases, shows 93% accuracy (sensitivity 96.6%; specificity 84.8%).  Conclusions p53 IHC shows excellent inter-laboratory/inter-observer agreement in EC biopsy specimens. Our preliminary results suggest that p53 IHC is a robust biomarker of ‘serous-like’ EC in biopsy material, especially as part of an algorithm.       

P53 IMMUNOHISTOCHEMISTRY AS A SURROGATE FOR TP53 MUTATIONAL ANALYSIS IN ENDOMETRIAL CANCER BIOPSIES

https://qmro.qmul.ac.uk/xmlui/bitstream/handle/123456789/69398/Manchanda_Abstract-P53-IMMUNOHISTOCHEMISTRY_Accepted_2018.pdf?sequence=7&isAllowed=y

P53 IMMUNOHISTOCHEMISTRY AS A SURROGATE FOR TP53 MUTATIONAL ANALYSIS IN ENDOMETRIAL CANCER BIOPSIES

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