title: PAX8 reliably distinguishes ovarian serous tumors from malignant mesothelioma.
abstract: Ovarian serous neoplasms can have morphologic overlap with malignant mesothelioma. The distinction is clinically important, yet most studies have failed to identify immunostains that reliably distinguish these 2 tumor types. Recently, transcription factor PAX8 was shown to be a sensitive and relatively specific marker for Müllerian tumors. In addition, some studies suggest that h-caldesmon is sensitive and specific for mesothelioma when compared with 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. Immunohistochemistry was carried out using PAX8 and h-caldesmon antibodies on archival tissue from 254 ovarian serous tumors and 50 mesothelial tumors. Nuclear and cytoplasmic immunoreactivity were considered positive for PAX8 and h-caldesmon, respectively. PAX8 staining was present in 99% of high-grade serous ovarian carcinomas and all (100%) low-grade ovarian carcinomas and serous borderline tumors; however, only 74% of these cases (188/254) were diffusely positive in more than 50% of tumors cells, and intensity ranged from strong to weak. None of the pleural malignant mesotheliomas were reactive with PAX8. However, 2/23 (9%) peritoneal malignant mesotheliomas showed focal and/or weak staining for PAX8; the remaining cases were negative. Two well-differentiated papillary mesotheliomas and 1 multicystic mesothelioma each showed some staining for PAX8. h-caldesmon was negative in all serous neoplasms and all mesothelial neoplasms, except 1 pleural malignant mesothelioma which showed patchy immunoreactivity. Strong PAX8 staining is highly specific (P<0.00001) for ovarian serous tumors when compared with malignant mesotheliomas of the peritoneum and pleura. The presence of weak staining for PAX8 in the 3 "noninvasive" mesotheliomas questions the use for PAX8 in this differential diagnosis. On the basis of this study, h-caldesmon is not a useful marker for mesothelioma.
authors.affiliation: Department of Pathology Section, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Laury
authors.forename: Jason L
authors.initials: JL
authors.lastname: Hornick
authors.forename: Ruth
authors.initials: R
authors.lastname: Perets
authors.forename: Jeffrey F
authors.initials: JF
authors.lastname: Krane
authors.forename: Joseph
authors.initials: J
authors.lastname: Corson
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Hirsch
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002148:Calmodulin-Binding Proteins / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D008654:Mesothelioma / Q000175:diagnosis* / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D010997:Pleural Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D002148:Calmodulin-Binding Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors