PAX8 and CDX2 Can Stain Positive in Breast Cancer, Risking Misdiagnosis of Tumor Origin
This study found that PAX8 and CDX2 · immunohistochemical markers traditionally considered specific to gynecologic/renal and gastrointestinal carcinomas, respectively · are occasionally expressed in breast cancer (4.6% for PAX8, 1.8% for CDX2). In rare cases staining was strong and diffuse, which caused diagnostic confusion about the primary tumor site. The findings underscore that pathologists must use additional markers such as TRPS1 when determining tumor origin, rather than relying on PAX8 or CDX2 alone.
The original study
Unusual staining of immunohistochemical markers PAX8 and CDX2 in breast carcinoma: a potential diagnostic pitfall.
- Authors
- Shen T, Zhao J, Zhao M, Taggart MW, Ramalingam P, Gong Y, et al.
- Journal
- Human pathology
- Type
- Journal Article, Review, Research Support, Non-U.S. Gov't
- PMID
- 35417734
Original abstract
Knowing the sensitivity and specificity of tissue-specific immunohistochemical markers is crucial for accurate determination of the primary tumor site. PAX8 has been used as a diagnostic marker for carcinomas of the gynecologic tract, kidney, and thyroid gland, and CDX2 has been used as a marker of gastrointestinal carcinoma. Neither is considered a marker for breast carcinoma (BC). However, we have encountered BCs that express PAX8 or CDX2, some of which caused diagnostic confusion. We investigated the immunohistochemical staining frequency of PAX8 and CDX2 in BC. We identified 237 BCs for which PAX8 staining results were reported (102 primary and 135 metastatic BCs); seven primary and four metastatic BCs (4.6%) were positive for PAX8, with various intensities and staining patterns. CDX2 staining results were reported for 271 BCs (78 primary and 193 metastatic); four primary BCs and one metastatic BC (1.8%) were positive for CDX2, ranging from focal and weak to diffuse and strong. We also stained primary invasive BCs with PAX8 and CDX2 using tissue microarrays. None of the 332 PAX8-stained cases was positive, while one of 143 CDX2-stained cases was positive. Four PAX8-positive and three CDX2-positive cases were stained with TRPS1, and all were positive for TRPS1. In addition, we reviewed the literature for PAX8 and CDX2 expression in BCs and found 5.5% PAX8-positive BCs (90/1625) in 17 studies and 0.8% CDX-2 positive BCs (7/909) in 20 studies. PAX8 and CDX2 are infrequently expressed in BC by immunohistochemistry, and in rare cases, the staining can be strong and diffuse. Additional diagnostic markers are necessary and helpful in distinguishing breast from other primary origins.