The Significance Of BRAF Mutation And Immunohistochemical Expression Of CK19, Galectin-3, TRβ1, B-raf In The Pathological Diagnosis And Prognosis Of Papillary Thyroid Carcinomas

Objective:To investigate the clinicalpathological significance of BRAF mutation and theexpression of CK19, Galectin-3, TRβ1, B-raf in the pathological diagnosis of papillarythyroid lesions and the prognosis of papillary thyroid carcinomas.Methods:Part1:101papillary thyroid lesions were collected in this section of study whichincluded66papillary thyroid carcinoma (PTC) and35papillary thyroid hyperplasia(PTH). The BRAF mutation was tested by RT-PCR. The value of BRAF mutaion in thediagnosis of PTC and the correlation between clinicopathological significance and thepresence of BRAF were evaluated.Part2:221papillary thyroid lesions including151PTC and70PTH were evaluated byimmunihistochemistry for the expression of CK19, Galectin-3, TRβ1and B-raf in orderto evaluate the role of their expression in the differential diagnosis between PTC andPTH. The relationship between their expression and some clinicopathological featuresas well as BRAF mutation in PTC was also analyzed.Results:Part1:1. BRAF mutation was found in60.6%(40/66) PTCs and0(0/35) PTHs respectively.The difference was statistically significant (p＜0.0001).2. BRAF mutation was closely associated with age (p=0.0004), mutifocality (p=0.0031),lymph nodal metastasis (p=0.0082) and higher clinical stage (p=0.0254). No associationwas found between BRAF mutation and patient gender or tumor size. 3. The BRAF gene mutation showed significant difference among the histologicalvariants (tall cell variant,85.7%; oncocytic variant,77.8%; classical,66.7%; papillarymicrocacinoma,61.1%; follicular variant,18.2%; p=0.0208).Part2:1. CK19was positive in145PTC cases (96.0%,145/151) and26PTH cases (37.1%,26/70). The positivity rate of Galectin-3was94.7%(143/151) in PTC and25.7%(18/70)in PTH group respectively. TRβ1was positive in31PTC cases (20.5%,31/151) and67PTH cases (95.7%,67/70). All three markers showed significantly higher expression inPTC than in PTH (p<0.05). The positivity rate of B-raf was84.8%(128/151) in PTCand81.4%(57/70) in PTH group respectively, which shows no significant differencebetween the two groups.2. Galectin-3was a more specific but less sensitive marker than CK19fordifferentiating PTC from PTH. TRβ1is more specific but less sensitive than Galectin-3in differential diagnosis of PTC versus PTH. In addition, co-expression of either two ofthe three markers could greatly improve the specificity to97.4%(CK19and TRβ1) or98.7%(Galectin-3and TRβ1or CK19) in PTC versus PTH.3. No statistically significant correlation were found between the expression of CK19,TRβ1, B-raf and clinicalpathological features such as age, gender, tumor size,multifocality, lymph node metastasis and stage. Galectin-3was associated with lymphnode metastasis(p=0.0404) and clinical stage(p=0.0113).4. There was no significant correlation between CK19,Galectin-3,TRβ1or B-raf andBRAF mutation in PTC.Conclusions:Part1:1. The rate of BRAF mutation was high in PTC cases, the detection of BRAF mutationcould help in the differential diagnosis between benign and malignant thyroid papillarylesions.2. BRAF mutation in PTC was not significantly correlated with gender or tumor size, but was significantly correlated with older age, mutifocality, lymph nodal metastasis,higher clinical stage and different histologic variants.Part2:1. CK19was a sensitive marker for the diagnosis of PTC. But, its specificity was lower;while the diagnostic sensitivity and specifity of Galectin-3were both high for PTC.2. TRβ1had higher expression rate in PTC than in PTH, was more specific for thedifferential diagnosis of PTC from PTH when compared with Galectin-3.3. There is no significant difference in the expression of B-raf between PTH and PTCcases.4. There was no significant correlation between the expression of CK19, Galectin-3,TRβ1, B-raf and BRAF mutation in PTC.5. TRβ1and B-raf expression showed no close correlation with the tumor size, number,lymph node metastasis, sex, age and tumor clinical stage. Galectin-3was associatedwith lymph node metastasis (p=0.0404) and advanced clinical stage (p=0.0113).