The Profile of Heparanase Expression Distinguishes Differentiated Thyroid Carcinoma from Benign Neoplasms.
BACKGROUND
The search for a specific marker that could help to distinguish between differentiated thyroid carcinoma and benign lesions remains elusive in clinical practice. Heparanase (HPSE) is an endo-beta-glucoronidase implicated in the process of tumor invasion, and the heparanase-2 (HPSE2) modulates HPSE activity. The aim of this study was to evaluate the role of heparanases in the development and differential diagnosis of follicular pattern thyroid lesions.


METHODS
HPSE and HPSE2 expression by qRT-PCR, immunohistochemistry evaluation, western blot analysis and HPSE enzymatic activity were evaluated.


RESULTS
The expression of heparanases by qRT-PCR showed an increase of HPSE2 in thyroid carcinoma (P = 0.001). HPSE activity was found to be higher in the malignant neoplasms than in the benign tumors (P<0.0001). On Western blot analysis, HPSE2 isoforms were detected only in malignant tumors. The immunohistochemical assay allowed us to establish a distinct pattern for malignant and benign tumors. Carcinomas showed a typical combination of positive labeling for neoplastic cells and negative immunostaining in colloid, when compared to benign tumors (P<0.0001). The proposed diagnostic test presents sensitivity and negative predictive value of around 100%, showing itself to be an accurate test for distinguishing between malignant and benign lesions.


CONCLUSIONS
This study shows, for the first time, a distinct profile of HPSE expression in thyroid carcinoma suggesting its role in carcinogenesis.
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil; Head and Neck Surgery Department, Faculdade de Medicina do ABC, Santo André, Brazil; Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Leandro Luongo
LL
Matos
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil; Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Eloah Rabello
ER
Suarez
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil.
Thérèse Rachell
TR
Theodoro
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil.
Damila Cristina
DC
Trufelli
Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Carina Mucciolo
CM
Melo
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil.
Larissa Ferraz
LF
Garcia
Pathology Department, Pathos Medical Diagnosis, São Paulo, Brazil.
Olivia Capela Grimaldi
OC
Oliveira
Universidade Cidade de São Paulo (Unicid), São Paulo, Brazil.
Maria Graciela Luongo
MG
Matos
Head and Neck Surgery Department, Faculdade de Medicina do ABC, Santo André, Brazil.
Jossi Ledo
JL
Kanda
Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Helena Bonciani
HB
Nader
Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil; Laboratory of Molecular and Translational Endocrinology, Endocrinology and Metabolism Discipline, Universidade Federal de São Paulo, São Paulo, Brazil.
João Roberto Maciel
JR
Martins
Biochemistry Department, Faculdade de Medicina do ABC, Santo André, Brazil; Biochemistry Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Maria Aparecida Silva
MA
Pinhal
D003937:Diagnosis, Differential; D005260:Female; D005966:Glucuronidase / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000099175:Heparanase
D005966:Glucuronidase; D000099175:Heparanase