Abstract 4644: A cell-line based TP53 expression pattern control panel with interobserver variability and next-generation sequencing analysis

Abstract

Abstract Introduction: TP53 gene mutation status is known to be manifested through distinct p53 immunohistochemical staining patterns; diffuse, wild-type and null. This stratified staining pattern is routinely utilized in subtyping ovarian and endometrial cancer subtypes and distinguishing low- and high-grade serous carcinoma. Experimental Procedure: Three ovarian cancer cell lines were used in the construction of an immunohistochemical control panel slide that highlights each respective TP53 expression pattern. Cell lines were expanded, harvested and resuspended in agarose gel and subsequently sectioned onto a microscope slide. Procured tissue specimens were submitted along with either standard control tissue or the TP53 cell line control panel to pathologists of varying experience. Next-generation sequencing analysis was performed on cases in which there was discordance in expression pattern interpretation. Results: Interobserver variability was assessed on 44 samples between five raters of varying experience. The results were similar with the use of the TP53 expression panel (Fleiss kappa= 0.6 vs 0.53). Next-generation sequencing analysis demonstrated low-frequency variant mutations in cases in which there was reviewer discordance. Conclusion: This study suggests the addition of a TP53 cell line expression pattern control panel could potentially increase diagnostic accuracy for ovarian and endometrial cancer subtypes and distinguishing ovarian low-grade and high-grade serous carcinoma. The cell line control has refined quality assurance potential for antibody optimization.This cell line control panel has the potential to be utilized in routine immunohistochemical staining with difficult to interpret p53 expression patterns directed to submission for next-generation sequencing. Citation Format: Yaling Zhou, Sorana Raiciulescu, Viqar Syed, Patrick Malafronte, Justin Wells, Mica Grantham, Michael Allgaeuer, Heping Gong, Joel Moncur, Deyin Xing, John D. Andersen. A cell-line based TP53 expression pattern control panel with interobserver variability and next-generation sequencing analysis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4644. doi:10.1158/1538-7445.AM2017-4644