基质金属蛋白酶-2和骨唾液蛋白在甲状腺乳头状癌组织中的表达及其与淋巴结转移的关系

Matrix metalloproteinases-2 and bone sialoprotein protein expression in papillary thyroid carcinoma and its association with lymph node metastasis

目的检测基质金属蛋白酶(MMP)-2和骨唾液蛋白(BSP)在甲状腺乳头状癌(PTC)组织中的免疫组织化学表达情况,探讨两者的表达与颈淋巴结转移的关系。方法收集2010年4月—2011年10月间行甲状腺癌根治+颈侧方淋巴结清扫或中央组淋巴结清扫的121例PTC患者的石蜡切片,另取甲状腺良性结节和癌旁组织石蜡切片各30例,采用链霉素抗生物素蛋白-过氧化物酶连结(SP)法免疫组织化学染色对MMP-2和BSP进行染色,观察MMP-2和BSP免疫组织化学表达情况。结果 PTC组织中的MMP-2表达阳性率为75.2%(91/121),显著高于甲状腺良性结节组织中的56.7%(17/30)和癌旁组织中的26.7%(8/30,P值均<0.05);PTC合并颈侧方淋巴结转移者的MMP-2表达阳性率为80.0%(28/35),显著高于PTC合并中央组淋巴结转移者的72.7%(40/55)和无淋巴结转移者的74.2%(23/31,P值均<0.05);MMP-2对诊断甲状腺乳头状癌的灵敏度、特异度、阳性预测值和阴性预测值分别为75.2%(91/121)、73.3%(22/30)、91.9%(91/99)和42.3%(13/30)。PTC组织中的BSP表达阳性率为82.6%(30/35),显著高于甲状腺良性结节组织中的70.0%(21/30)和癌旁组织中的50.0%(15/30,P值均<0.05);PTC合并颈侧方淋巴结转移、PTC合并中央组淋巴结转移和无淋巴结转移者的BSP表达阳性率分别为85.7%(30/35)、80.0%(44/55)和83.9%(26/31),三者间的差异无统计学意义(P值均>0.05);BSP对诊断甲状腺乳头状癌的灵敏度、特异度、阳性预测值和阴性预测值分别为82.6%(100/121)、50.0%(15/30)、87.0%(100/114)和30.0%(9/30)。Pearson相关性分析显示,PTC组织中MMP-2与BSP表达具有相关性(C=0.86,P<0.001)。结论 MMP-2和BSP可作为临床诊断甲状腺乳头状癌的辅助指标,且MMP-2对筛选PTC颈侧方淋巴结转移高危人群具有潜在的临床意义。

Objective To detect the expression of matrix metalloproteinase （MMP）-2 and bone sialoprotein （BSP） in papillary thyroid cancer （PTC） by immunohistochemistry, and to explore the relationship between MMP-2 and BSP levels and lymph node metastases in PTC. Methods Immunohistochemical staining with the paraffin sections for MMP-2 and BSP were performed in 121 PTC patients who received PTC radical surgery plus central or lateral cervical lymph node dissection between April 2010 and October 2011. Meanwhile, 30 benign thyroid nodules and 30 adjacent normal follicular epithelium specimens were collected for comparison. Results The expression of MMP-2 in PTC was 75.2% （91/121）, which was significantly higher than that in benign thyroid nodules （56.7% [17/30]） and tumor adjacent tissues （26.7% [8/30], both P〈O. 05）. The expression of MMP-2 in PTC patients with cervical lateral lymph node metastasis was 80.0% （28/35）, which was significantly higher than that in the patients with central lymph node metastasis （72.7% [40/55]） and without lymph node metastasis （74.2% [23/31], both P〈0.05）. The sensitivity, specificity, positive predictive value and negative predictive values in the diagnosis of thyroid papillary carcinoma by MMP-2 were 75.2% （91/121）, 73.3% （22/30）, 91.9% （91/99） and 42.3% （13/30）, respectively. The expression rate of BSP in PTC was 82.6% （30/35）, which was significantly higher than that in benign thyroid nodules （70.0% [21/30]） and tumor adjacent tissues （50.0% [15/30], both P〈0.05）. The expression of BSP in PTC patients with cervical lateral lymph node metastasis, with central lymph node metastasis and without lymph node metastasis were 85.7 % （30/ 35）, 80.0% （44/55） and 83.9% （26/31）, respectively （all P^0.05）. The sensitivity, specificity, positive predictive value and negative predictive values in the diagnosis of thyroid papillary carcinoma by BSP were 82.6% （100/121）, 50.0% （ 15/30）, 87.0% （100/114） and 30.0% （9/30）, respectively. Pearson correlation analysis showed a close correlation between MMP-2 and BSP in PTC tissues （C = 0.86, P〈0.001）. Conolusion MMP- 2 and BSP can be used for the auxiliary diagnosis of PTC. MMP-2 has potential clinical significance in screening high risk population of lateral cervical lymph node metastasis in PTC. （Shanghai Med J, 2014, 37： 340-343）