The Importance of WT1 Immunohistochemistry in Gynecological Cancer
WT1 (Wilms Tumor 1) immunohistochemistry is primarily valuable as a diagnostic marker to determine the origin of serous carcinomas, with diffuse WT1 positivity strongly favoring a tubo-ovarian origin while negative staining suggests a uterine primary. 1
Diagnostic Applications of WT1 IHC
Distinguishing Primary Site of Serous Carcinomas
- Most tubo-ovarian serous carcinomas (80-100%) exhibit diffuse nuclear positivity with WT1 1
- Most uterine serous carcinomas (80-93%) are WT1 negative 1
- This distinction is critical when there is simultaneous involvement of both the uterus and ovaries, which impacts treatment decisions and prognosis 1
Differential Diagnosis Between Histological Subtypes
- WT1 helps differentiate ovarian serous carcinoma (typically WT1+) from ovarian endometrioid carcinoma (typically WT1-) 2
- This distinction is particularly valuable in poorly differentiated tumors where morphological features may be ambiguous 2
Panel Approach for Gynecological Cancer Diagnosis
- WT1 should be used as part of a diagnostic panel rather than in isolation 3
- First-line panel should include PAX8, WT1, CK7, and CK20 to distinguish between different types of gynecologic carcinomas 3
- PAX8+/WT1+/CK7+/CK20- profile strongly suggests high-grade serous ovarian carcinoma 3
- PAX8+/WT1-/CK7+/CK20- profile suggests endometrioid or clear cell carcinoma 3
Distinguishing Between Serous and Mesothelial Proliferations
- Both serous and mesothelial proliferations are typically WT1 positive 1
- Additional markers are needed for this differential diagnosis:
- BerEP4, ER, and PAX8 (usually positive in serous proliferations)
- Calretinin and CK5/6 (usually positive in mesothelial proliferations) 1
Prognostic Value of WT1 in Gynecological Cancers
High-Grade Serous Ovarian Carcinoma
- WT1 expression has been identified as an independent prognostic factor in high-grade serous ovarian carcinoma 4
- High WT1 expression is associated with improved overall survival (OS) and progression-free survival (PFS) 4
- This prognostic value is independent of age, stage, and residual tumor 4
Other Gynecological Cancers
- Meta-analysis data suggests that WT1 overexpression may be associated with poor disease-specific survival and progression-free survival in some gynecological cancers 5
- The prognostic significance varies by cancer type and requires further investigation 5
Therapeutic Implications
WT1 as a Target for Immunotherapy
- WT1 is being investigated as a target antigen for cancer immunotherapy 6
- Early clinical trials of WT1 peptide vaccines in gynecological cancers have shown promise in stabilizing disease 6
- Case reports suggest potential clinical benefit in intractable ovarian cancer 6
Limitations and Caveats
- Some overlap exists in WT1 expression patterns:
- Interpretation should always consider the entire clinical and pathological context 3
- WT1 has limited value in distinguishing between primary ovarian and uterine endometrioid carcinomas as both are typically WT1 negative 1, 2
Best Practice Recommendations
- Use WT1 as part of a comprehensive IHC panel rather than in isolation 3
- Consider WT1 expression pattern in conjunction with clinical presentation and morphological subtype 1
- Recognize that WT1 is the recommended marker to determine the origin of serous cancer 1
- Understand that WT1 positivity in a serous neoplasm favors a tubo-ovarian origin, while negative staining suggests a uterine primary 1
- Be aware of the potential prognostic implications of WT1 expression, particularly in high-grade serous ovarian carcinoma 4
WT1 immunohistochemistry has evolved from a purely diagnostic tool to a marker with potential prognostic and therapeutic implications in gynecological cancers, making it an essential component of the pathological evaluation of these malignancies.