PAX8 Distinguishes Serous Ovarian Neoplasms from Malignant Mesothelioma with High Sensitivity and Specificity
AR Laury, JL Hornick, JM Corson, JF Krane, R Drapkin, MS Hirsch. Brigham and Womens Hospital, Boston, MA; Dana Farber Cancer Institute, Boston, MA
Background: Ovarian serous neoplasms, whether primary in the peritoneum or metastatic to the pleura, can have morphologic overlap with mesothelioma. This distinction is critical clinically, yet most studies have failed to identify immunostains that reliably distinguish between these two tumor types. Recently, the transcription factor PAX8 has been shown to be sensitive and relatively specific for Mullerian tumors. Additionally, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared to serous ovarian tumors. The goal of this study was to evaluate whether PAX8 and h-caldesmon expression can successfully distinguish mesothelioma from serous ovarian tumors.
Design: Immunohistochemistry was performed after pressure cooker antigen retrieval using rabbit anti-PAX8 polyclonal (Proteintech; 1:800) and mouse anti-h-caldesmon monoclonal (DAKO; 1:300) antibodies on archival tissue from 254 ovarian serous tumors (152 high grade serous carcinomas, 10 low grade serous carcinomas, and 92 serous borderline tumors) and 54 mesothelial tumors (24 pleural malignant mesotheliomas, 27 peritoneal malignant mesotheliomas, 2 well-differentiated papillary mesotheliomas, and 1 multicystic mesothelioma). Only nuclear and cytoplasmic immunoreactions were considered positive for PAX8 and h-caldesmon, respectively.
Results: Diffuse and strong PAX8 staining was present in 151/152 (99%) high grade serous ovarian carcinomas, and all (100%) low grade ovarian carcinomas and serous borderline tumors. None of the pleural malignant mesotheliomas were reactive with PAX8. 3/27 (11%) peritoneal malignant mesotheliomas demonstrated focal, weak staining for PAX8; the remaining 24 cases were negative. The 2 well-differentiated mesotheliomas and the 1 multicystic mesothelioma each demonstrated focal, weak staining for PAX8. h-caldesmon was negative (with appropriate positive internal controls) in all cases evaluated, including all mesotheliomas.
Conclusions: Strong PAX8 staining is highly specific (p<0.00001) for ovarian serous carcinoma and serous borderline tumors when compared to malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "non-invasive" mesotheliomas raises questions about cell lineage of these tumors, as well as the utility for PAX8 in this differential diagnosis. Based on this study, h-caldesmon is not a useful marker for mesothelioma.
Category: Gynecologic & Obstetrics
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 177, Wednesday Afternoon