Diagnostic and Prognostic Role of WT1 Immunohistochemical Expression in Uterine Carcinoma: A Systematic Review and Meta-Analysis across All Endometrial Carcinoma Histotypes

Abstract

Background: The diagnostic role of Wilms’ tumor 1 (WT1) is well known in gynaeco-pathological setting, since it is considered a specific marker of serous histotype and adnexal origin. Moreover, its oncogenic role has been recently highlighted in many cancers and it has also been regarded as a promising target antigen for cancer immunotherapy. However, the relationship between its expression and prognostic role in uterine cancer remains unclear. We analyzed the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma by completing a search using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines and the PICOS (Participants, Intervention, Comparison, Outcomes, Study Design) model through PubMed, Scopus and Web of Science databases to identify studies that fit our search criteria. The objective of the current meta-analysis was to investigate the diagnostic and prognostic role of WT1 expression in patients with uterine carcinoma. Materials and Methods: A literature search was performed of the PubMed, Scopus, and Web of Science databases for English-language studies published from January 2000 to April 2020. Studies were considered eligible if they evaluated the WT1 expression in uterine carcinoma. Results: In total, 35 articles were identified that used uterine carcinoma criteria and provided data for 1616 patients. The overall rate of WT1 expression in uterine carcinoma was 25%. The subgroup analysis of uterine cancer types revealed that WT1 was expressed differently among different histotypes (endometrioid, clear cell, serous carcinoma and carcinosarcoma). Discussion and Conclusions: The WT1 immunohistochemical expression is not limited to serous histotype and/or ovarian origin. In fact, a significant proportion of endometrial adenocarcinomas can also show WT1 immunoreactivity. Moreover, our study suggests that WT1 may be a potential marker to predict the prognosis of patients with uterine cancer, but more studies are needed to confirm its role in clinical practice.

New Pathological and Clinical Insights in Endometrial Cancer in View of the Updated ESGO/ESTRO/ESP Guidelines

“…There are other morphologic factors that might have an independent prognostic value in EEC, such as a tumor budding, microcystic, elongated, and fragmented (MELF) pattern of invasion and WT1 immunohistochemical expression [ 29 , 30 , 31 ], although data in this regard are scarce. The prognostic significance of these factors, their reproducibility and their possible integration in the current risk stratification system need to be further investigated.…”

Evaluation of the incidence and clinical significance of WT-1 expression in uterine serous carcinoma

“…Similarly to the aforementioned reports, these authors reported worse overall, disease-specific and progression free survival across the entire cohort of endometrial cancer patients expressing WT-1. Additionally, when looking only at cases of USC, the authors observed a significant decline in OS with WT-1 expression ( Angelico et al, 2020 ). Although the results of current study do not replicate these findings, it is important to again note that the reports by Hedley et al and Dupont et al represent only 29 patients in total and therefore the results are difficult to generalize to the population as a whole.…”

Clear cell endometrial carcinoma precursors: presentation of two cases and diagnostic issues

“…Nuclear pleomorphism and mitotic activity are often not striking [ 2 , 3 ]. By immunohistochemistry, CC-EC is characterized by negativity for estrogen receptor (ER), progesterone receptor (PR) and WT1, and positivity for Napsin A, HNF1β (hepatocyte nuclear factor 1, less specific in the endometrium than in the ovary), and α-methylacyl-coenzyme-A racemase (AMACR, still not validated) [ 2 – 5 ].…”