| Objective:To observe the expression of leptin and leptin receptor (OB-R) in thyroid carcinoma and to correlate the expression of these two proteins with clinicopathologic characterstics.Methods:173specimens were obtained from patients who received surgery for thyroid carcinoma (TC) at Fudan University Shanghai Cancer Center during the period between2003and2012, which comprising93cases of papillary thyroid carcinoma (PTC),41cases of follicular thyroid carcinoma (FTC),25cases of medullar thyroid carcinoma (MTC), and14cases of undifferentiated thyroid carcinoma (UTC). Besides,15cases of nodular goiter (NG),10cases of Hashimoto’s thyroiditis (HT),17cases of follicular adenoma (FA) and120samples of normal thyroid tissue adjacent to the carcinoma were employed as the control group. All of the patients did not receive any pre-operative anti-tumor treatment. Expression of leptin and OB-R was detected in a tissue microarray cohort through the En Vision+immunohistochemical staining manually.Results:1. No expression of leptin and OB-R were seen in the normal thyroid tissue adjacent to the carcinomas. The expression rate of leptin in NG, HT, FA and TC was0%,10%,11.8%and37.2%, respectively, with a statistical difference (p=0.002). The expression rate of OB-R in NG, HT, FA and TC was0%,20%,18.8%and52.7%, respectively, with a statistical difference (p<0.001).2. The expression rate of leptin in PTC, FTC, MTC and UTC was42.2%,25.7%,25%and50.0%, with no significant difference (p=0.184). The expression rate of OB-R in PTC, FTC, MTC and UTC was57.1%,40.0%,55.0%, and57.1%, with no significant difference (p=0.326).3. In PTC, the expression of leptin correlated with older age, larger tumor size, lymph nodal metastasis and advanced stage (p=0.013, p=0<0.001, p=0.001and p=0.002respectively), but was not associated with other parameters, including gender, multifocality, accompanying diseases (including NG, HT, and FA) and distant metastasis; The expression of OB-R correlated with larger tumor size, lymph nodal metastasis and advanced stage (p=0.001, p=0.007, and p=0.0017respectively), but was not associated with other parameters, including age, gender, multifocality, accompanied diseases and distant metastasis. In addition, there is a correlation between the expression of leptin and OB-R (r=0.636, p<0.001). Patients with either leptin or OB-R expression had a worse5year disease-free survival rate than leptin or OB-R negative group (41%VS81%, p=0.015;55%VS77%, p=0.026). Nevertheless, neither leptin nor OB-R expression appeared to be an independent prognostic factor for disease-free survival in multivariate analysis.4. In FTC, neither leptin nor OB-R expression was associated with age, gender, tumor size, accompanying disease, distant metastasis and stage (p>0.05). Either leptin or Ob-R expression rate is higher in patients with lymph nodal metastasis as compared with patients without lymph nodal metastasis, but with no significant difference (p>0.05). The expression levels of leptin and OB-R were associated with each other (r=0.640, p<0.001). Patients with either leptin or OB-R expression had a better disease-free survival rate than negative group, but with no significant difference (p=0.281, p=0.240).5. In MTC, leptin expression was not associated with age, gender, tumor size, accompanied diseases, lymph nodal metastasis and stage. OB-R expression was associated with lymph nodal metastasis and advanced stage (p=0.008, p=0.034), but was not associated with other parameters, including age, gender, tumor size, multifocality, and accompanied diseases. The expression of leptin and OB-R were not associated with each other (r=0.058, p<0.808). Patients with either leptin or OB-R expression had a worse disease-free survival rate than negative group, but with no significant difference (p=0.389, p=0.773).6. In UTC, neither leptin nor OB-R expression was associated with age, gender, tumor size, accompanying disease, lymph nodal metastasis, distant metastasis and stage. The expression of leptin and OB-R were associated with each other (r=0.577, p=0.031). Patients with leptin expression had a better survival rate than negative group, but with no significant significance (p=0.096). However, patients with OB-R expression had a better survival rate than negative group, with statistical difference (p=0.046).Conclusions:1. The expression level of leptin and OB-R in TC (including PTC, FTC, MTC and UTC) is higher than that in the control group (including NG, HT and FA), suggesting leptin and OB-R may be related to the development of TC 2. The expression rate of either leptin or OB-R in PTC, FTC, MTC and UTC has no significant difference, which suggests these two proteins are not associated with the subtype or the degree of malignancy of TC.3. In PTC, the expression of leptin is associated with older age, larger tumor size, lymph nodal metastasis, advanced stage and poor disease free survival. The expression of OB-R is associated with larger tumor size, lymph nodal metastasis, advanced stage and poor disease free survival. These suggest the expression of leptin and/or OB-R in PTC is associated with the aggressiveness of the tumor, which may be used as prognostic markers.4. In FTC, no relashionshiop is found between the expression of either leptin or OB-R and the aggressiveness of the tumor, perhaps they might be the favorable prognostic markers.5. In MTC no relashionshiop is found between the leptin expression and the aggressiveness of the tumor, while OB-R expression is associated with lymph nodal metastasis and advanced stage, which infers expression of OB-R in MTC may be associated with neoplastic aggressiveness.6. In UTC, no relashionshiop is found between the expression of either leptin or OB-R and neoplasm aggressiveness. Conversely the expression of OB-R is associated with good survival, which suggests it might be a favorable prognostic marker in UTC.7. A correlation is seen between the expression of leptin and OB-R in TCs deriving from follicular epithelial cells, but no correlation is seen in TC deriving from C cells. |
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