Investigator
University Of Pittsburgh
A comprehensive analysis of SOX17 expression by immunohistochemistry in human epithelial tumors, with an emphasis on gynecologic tumors
Abstract Objectives The objective of this study was to evaluate SOX17, a transcription factor from the Sry high-mobility group–related box superfamily, as a diagnostic marker to determine site of origin using both whole-tissue sections and tissue microarrays (TMAs). Methods SOX17 immunohistochemistry was performed on gynecologic and nongynecologic tissues (N = 1004) using whole-tissue sections and both internally constructed and commercially available TMAs. SOX17 nuclear reactivity was scored as positive or negative on the whole-tissue sections and using the semiquantitative H score method on TMAs. Results Using both whole-tissue sections and TMAs, SOX17 was positive in 94% (n = 155) of endometrial tumors and 96% (n = 242) of ovarian tumors. All breast cases (n = 241) and vulvar/cervical squamous cell carcinomas (n = 150) were negative. Among 1004 tumors from 20 sites, the only organs with positive tumors were ovary, uterus, and testis. Conclusions SOX17 is a sensitive and specific marker for gynecologic origin in the tissues tested and may be a valuable adjunct to PAX8 and other commonly used markers to confirm endometrial or ovarian origin. SOX17 expression is lower in mucinous tumors, endocervical adenocarcinoma, high-grade neuroendocrine tumors, and undifferentiated/dedifferentiated endometrial carcinoma.
Change of Practice Patterns Following an Educational Comment on Reports of Benign-Appearing Endometrial Cells in Papanicolaou Tests
Abstract Objectives Since the publication of our study demonstrating high negative predictive values (>99% for women in their 40s) of benign-appearing endometrial cells (nEMCs), we have begun to include an educational comment in Papanicolaou (Pap) test reports with nEMCs that recommends routine periodic screening for asymptomatic premenopausal women (APW). The current study evaluated how the inclusion of this comment has affected clinical practice patterns at our institution. Methods The 2017 to 2019 database identified 175 reports containing the educational comment in women aged 45 to 54 years with a follow-up time of 11 to 37 months. Data, including age, menopause status, symptoms, imaging, and outcome, were collected. The procedure rate and the impact of clinical modifiers were assessed. Results Thirty-seven (20.6%) patients had biopsies within 6 months, which decreased from 48.1% as we previously reported. All nine (5%) APW with biopsies triggered only by nEMCs had benign histopathology. The remaining 28 biopsied patients had abnormal bleeding or a thickened endometrium, or they were postmenopausal, including a 53-year-old patient with complex atypical hyperplasia. None of the 138 patients with conservative follow-up developed atypical/malignant lesions. Conclusions A qualifying educational note included in Pap reports significantly reduced follow-up biopsies in APW. Optimal follow-up of nEMCs should be based on relevant clinical modifiers.