title: The Value of HBME-1 and Claudin-1 Expression Profile in the Distinction of BRAF-Like and RAS-Like Phenotypes in Papillary Thyroid Carcinoma.
abstract: This study compared the expression profile of HBME-1 and claudin-1 in 90 papillary thyroid carcinomas (PTCs) with respect to the tumor architecture and invasive growth as reflected in 46 BRAF-like, 31 non-invasive RAS, and 13 invasive RAS-like phenotypes. Individual tumors were given an expression score (max 300) by multiplying the percent positive tumor cells by the intensity score (range 0-3). The higher expression of HBME-1 and claudin-1 distinguished BRAF-like phenotype from RAS-like phenotype. The same correlation was also retained for both markers when comparing BRAF-like phenotype with non-invasive and invasive RAS-like phenotypes. The expression scores and positivity rates for both markers did not yield any statistical difference among BRAF-like PTCs. Except the higher positivity rate of HBME-1, invasive RAS-like tumors were not statistically different than their non-invasive counterparts with respect to the positivity rate of claudin-1 and the expression scores of both markers. A central lymph node dissection or selective lymph node sampling was available in 20 specimens. The absence of claudin-1 expression has not been a feature of lymph node metastasis in this series. Despite the limited number of nodal sampling, BRAF-like phenotype and claudin-1 positivity status have been considered the best determinants of positive predictive value and negative predictive value in the prediction of lymph node metastasis among variables, respectively. Adoption of the simplified architectural classification approach to PTCs showed distinct biomarker expression profile in this series; however, immunohistochemistry for HBME-1 and claudin-1 does not seem to be useful in the distinction of invasive RAS-like PTCs from their non-invasive counterparts. Given the overlapping molecular signatures within the RAS-like phenotype, further studies with additional biomarkers are still needed to identify distinct protein expression signatures of non-invasive RAS-like phenotype as this diagnostic category still remains a surgical diagnosis at this time.
authors.affiliation: Department of Pathology, Recep Tayyip Erdogan University, Rize, Turkey.
authors.forename: Hasan
authors.initials: H
authors.lastname: Gucer
authors.affiliation: Department of Pathology, Marmara University, Istanbul, Turkey.
authors.forename: Pelin
authors.initials: P
authors.lastname: Bagci
authors.affiliation: Department of Pathology, Recep Tayyip Erdogan University, Rize, Turkey.
authors.forename: Recep
authors.initials: R
authors.lastname: Bedir
authors.affiliation: Department of Pathology, Recep Tayyip Erdogan University, Rize, Turkey.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Sehitoglu
authors.affiliation: Department of Pathology, University Health Network, 200 Elizabeth Street, 11th floor, Toronto, Ontario, M5G 2C4, Canada. ozgur.mete2@uhn.ca.|Endocrine Oncology Site Group, The Princess Margaret Cancer Centre, Toronto, Canada. ozgur.mete2@uhn.ca.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada. ozgur.mete2@uhn.ca.
authors.forename: Ozgur
authors.initials: O
authors.lastname: Mete
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000096:biosynthesis; D002277:Carcinoma / Q000473:pathology*; D002291:Carcinoma, Papillary; D062445:Claudin-1 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000473:pathology*; D059467:Transcriptome; D055815:Young Adult; D000951:Antigens, Neoplasm
chemical_list: D014408:Biomarkers, Tumor; D062445:Claudin-1; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); C568108:CLDN1 protein, human; C432845:HBME-1 antigen; D000951:Antigens, Neoplasm; C117307:KRAS protein, human; C482119:BRAF protein, human
keywords: BRAF-like papillary carcinoma; Claudin-1; HBME-1; Lymph node metastasis; NIFTP; Papillary thyroid carcinoma; RAS-like papillary carcinoma