title: GATA3 Is a Sensitive and Specific Marker of Benign and Malignant Mesonephric Lesions in the Lower Female Genital Tract.
abstract: GATA3 is a transcription factor critical for embryogenesis, development, and cell differentiation. Recent studies have suggested that GATA3 is a sensitive and relatively specific biomarker for urothelial and breast carcinomas, with most Müllerian carcinomas being negative. We investigated GATA3 expression in mesonephric/Wolffian remnants and tumors in the female genital tract. A western blot was performed to assess specificity for the GATA3 antibody. GATA3 immunohistochemistry was performed on 59 formalin-fixed paraffin-embedded mesonephric samples, including 17 mesonephric remnants (MR; 11 cervical and 6 fallopian tube), 15 mesonephric hyperplasias, 21 mesonephric carcinomas, and 6 female adnexal tumors of probable Wolffian origin. Thirty conventional endocervical adenocarcinomas (ENDO-CA), 9 gastric-type cervical adenocarcinomas, and 165 endometrial adenocarcinomas (EM-CA) were also evaluated. GATA3 nuclear intensity and extent of staining was evaluated. The western blot revealed GATA3 expression in seminal vesicle and cell lines derived from breast and urothelial carcinomas, but not in other cell lines including ovarian, cervical, and endometrial cancers. All cervical MRs and mesonephric hyperplasias, 5/6 (83%) fallopian tube MRs, and 20/21 (95%) mesonephric carcinomas were GATA3 positive, although with great variability in both intensity (weak to strong) and extent (1+ to 3+) of staining. Only 1/6 (17%) female adnexal tumors of probable Wolffian origin showed weak multifocal staining. One of 30 (3%) usual-type ENDO-CAs and 3/165 EM-CAs exhibited weak-moderate GATA3 immunoreactivity; all gastric-type cervical adenocarcinomas were negative. GATA3 is a highly sensitive and specific marker for mesonephric lesions in the lower genital tract; however, its utility in the upper genital tract may be more limited. In addition, GATA3 can aid in distinguishing lower genital mesonephric lesions from usual-type and gastric-type ENDO-CAs and uterine EM-CAs.
authors.affiliation: *Department of Pathology, Division of Women's and Perinatal Pathology, Brigham and Women's Hospital †Harvard Medical School ‡Department of Medical Oncology, Dana Farber Cancer Institute ∥Department of Pathology, Massachusetts General Hospital, Boston, MA §Department of Pathology, Belfast Health and Social Care Trust, Belfast, Northern Ireland, United Kingdom.
authors.forename: Brooke E
authors.initials: BE
authors.lastname: Howitt
authors.forename: Megan M
authors.initials: MM
authors.lastname: Emori
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: Cynthia
authors.initials: C
authors.lastname: Gaspar
authors.forename: Justine A
authors.initials: JA
authors.lastname: Barletta
authors.forename: Marisa R
authors.initials: MR
authors.lastname: Nucci
authors.forename: W Glenn
authors.initials: WG
authors.lastname: McCluggage
authors.forename: Esther
authors.initials: E
authors.lastname: Oliva
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Hirsch
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001900:Boston; D045744:Cell Line, Tumor; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000378:metabolism* / Q000473:pathology; D005185:Fallopian Tube Neoplasms / Q000378:metabolism* / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018294:Neoplasms, Adnexal and Skin Appendage / Q000378:metabolism* / Q000473:pathology; D009660:Northern Ireland; D011237:Predictive Value of Tests; D014928:Wolffian Ducts / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human