Specific Pathology Features Enrich Selection of Endometrial Carcinomas for POLE Testing

Author:

Keyhanian Kianoosh1,Han Lucy2,Howitt Brooke E.3,Longacre Teri3

Affiliation:

1. Department of Pathology and Laboratory Medicine, University of Ottawa/The Ottawa Hospital, Ottawa, ON, Canada

2. Department of Pathology, California Pacific Medical Center, San Francisco

3. Department of Pathology, Stanford University, Stanford, CA

Abstract

Identification of ultramutated/POLE-mutated endometrial carcinomas (POLE M ECs) has important implications given its association with better prognosis. However, POLE mutation testing is not widely available. Our objective was to evaluate POLE M ECs versus POLE wild-type (POLE WT) ECs, within a cohort of consultation cases with features suggestive of an ultramutated phenotype. Consultation cases of EC that had undergone POLE hotspot mutation testing over a 3.5-year period were included. Tumor morphology and immunohistochemistry were reviewed for both groups. Chi-square test and t test were used for statistical analysis. Of 25 consultation cases, 12 harbored a POLE mutation (48%) and 13 were wild-type (52%). Patients with POLE M ECs were younger (59 vs. 71.3 y; P=0.01). Ambiguous histomorphology (5/12 vs. 1/13; P=0.04) and the presence of more than rare bizarre nuclei (8/12 vs. 2/12; P=0.01) differed significantly between POLE M and POLE WT ECs, respectively. In the POLE M group, one case (1/12) demonstrated PMS2 loss, and one (1/12) showed subclonal MLH1/PMS2 loss. Among POLE WT ECs, 3/13 (23%) showed MLH1/PMS2 loss. p53 was subclonally overexpressed in 4/10 POLE M and 1/13 POLE WT cases (P=0.06). Mutant p53 patterns were seen in 1/10 POLE M versus 6/13 of POLE WT ECs, respectively (P=0.06). Within our cohort, the specificity of ambiguous histomorphology, bizarre nuclei, subclonal biomarker expression, and marked tumor-infiltrating lymphocytes for POLE M EC was 83%, 80%, 80%, and 71%, respectively. Where universal POLE testing is not available, these data suggest that morphologic screening (particularly ambiguous histomorphology and the presence of more than rare bizarre nuclei) can be useful for selective enrichment of ECs for POLE testing.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Pathology and Forensic Medicine,Surgery,Anatomy

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3