title: Cytoplasmic localization of the paired box gene, Pax-8, is found in pediatric thyroid cancer and may be associated with a greater risk of recurrence.
abstract: The paired box-8 protein (Pax-8) has been observed in the nucleus of normal adult thyroids, follicular adenomas, follicular thyroid cancers, and papillary thyroid cancers (PTC) but not undifferentiated thyroid cancers. To our knowledge, Pax-8 has not been studied in pediatric thyroid cancer. Because of the more favorable prognosis for PTC in children compared to young patients, we hypothesized that Pax-8 expression might be different in pediatric thyroid cancers. To test this, we stained 47 thyroid lesions from children and young patients for Pax-8. Pax-8 was located in the cytoplasm (cPAX) or nucleus (nPAX) in the majority of samples. There was no significant difference in nPAX between benign and malignant lesions. However, cPAX was more commonly seen in PTC than autoimmune diseases (p = 0.01) and the intensity of cPAX staining correlated with tumor size (p = 0.041), metastasis, age, completeness of resection, local invasion, and tumor size (MACIS) scores (p = 0.045), and the presence of invasion, metastasis, recurrence, or persistence (p = 0.012). Disease-free survival was significantly reduced for cancers with intense cPAX staining (p = 0.0003). These data show that cPAX is common in PTC, and although limited by small sample size, suggest an association with higher MACIS scores, an aggressive clinical course, and an increased risk of clinically evident recurrence for children and young patients.
authors.affiliation: Department of Pediatrics, Uniformed Services School of the Health Sciences, Bethesda, Maryland 20814, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Scouten
authors.forename: Aneeta
authors.initials: A
authors.lastname: Patel
authors.forename: Richard
authors.initials: R
authors.lastname: Terrell
authors.forename: Henry B
authors.initials: HB
authors.lastname: Burch
authors.forename: Victor J
authors.initials: VJ
authors.lastname: Bernet
authors.forename: R Michael
authors.initials: RM
authors.lastname: Tuttle
authors.forename: Gary L
authors.initials: GL
authors.lastname: Francis
mesh_terms: D000293:Adolescent; D000328:Adult; D014408:Biomarkers, Tumor; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D002648:Child; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D004268:DNA-Binding Proteins / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology; D009687:Nuclear Proteins / Q000235:genetics*; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors; D012306:Risk; D013964:Thyroid Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D015534:Trans-Activators