# Study of High Levels of Wilms’ Tumor 1 (WT1) Expression in Ovarian Cancers

## TL;DR

This study shows that high levels of the WT1 protein are strongly linked to a specific type of ovarian cancer called serous carcinoma and may help in diagnosis and predicting disease progression.

## Contribution

The study demonstrates that WT1 is a reliable marker for serous ovarian carcinoma and its association with advanced tumor stages.

## Key findings

- WT1 positivity is predominantly observed in serous carcinomas and absent in mucinous and seromucinous tumors.
- WT1 positivity is significantly associated with advanced FIGO stages in serous carcinomas.
- WT1 is a useful marker for distinguishing serous tumors from other ovarian neoplasms.

## Abstract

Background

Ovarian cancer is a major cause of cancer-related mortality among women and remains a significant diagnostic and therapeutic challenge due to its heterogeneous nature, absence of effective screening strategies, and frequent presentation at advanced stages. Surface epithelial ovarian tumors constitute the largest group of ovarian neoplasms and account for the majority of malignant cases. These tumors encompass multiple histological subtypes with distinct morphological features, biological behavior, and prognostic implications. Accurate histopathological classification supported by immunohistochemical markers is, therefore, essential for diagnosis and prognostication. Wilms’ tumor 1 (WT1) is a zinc finger transcription factor involved in cellular proliferation, differentiation, apoptosis, and regulation of the cell cycle. Although initially described as a tumor suppressor gene, WT1 has been shown to demonstrate oncogenic behavior in several malignancies, particularly ovarian cancer, and is strongly associated with serous ovarian carcinoma.

Methods

This prospective observational study was conducted over a two-year period and included 300 histopathologically confirmed epithelial ovarian tumors. Borderline and malignant epithelial ovarian tumors were included, while benign ovarian tumors, non-epithelial ovarian tumors, inflammatory lesions, and metastatic tumors involving the ovary were excluded. Surgically excised specimens and biopsy samples obtained during routine clinical care were fixed in formalin and processed using standard histopathological techniques. Sections were stained with hematoxylin and eosin for microscopic evaluation and tumor classification. Immunohistochemical staining for WT1 was performed on representative tissue sections, and tumors were categorized as WT1-positive or WT1-negative based on nuclear immunoreactivity. WT1 positivity was analyzed for its association with histological subtype and International Federation of Gynecology and Obstetrics (FIGO) stage.

Results

Malignant tumors constituted the majority of cases, while borderline tumors accounted for a smaller proportion. Serous tumors were the most common histological subtype, followed by mucinous tumors, seromucinous tumors, and poorly differentiated adenocarcinomas. WT1 positivity demonstrated a distinct distribution across tumor subtypes. Nuclear WT1 positivity was predominantly observed in serous carcinomas, while mucinous and seromucinous tumors were WT1-negative. Borderline serous tumors showed WT1 positivity less frequently. WT1 positivity was significantly associated with advanced FIGO stages in serous carcinomas.

Conclusion

WT1 is a sensitive and reliable immunohistochemical marker for serous ovarian carcinoma and is useful in distinguishing serous tumors from other epithelial ovarian neoplasms. The association between WT1 positivity and advanced tumor stage suggests a potential prognostic role. Incorporation of WT1 immunohistochemistry into routine diagnostic practice may enhance tumor classification and provide insights into disease progression in ovarian cancer.