Expression Of MMP-2, TIMP-2, Collagen Type Ⅳ, And Their Relationships With Tumor Invasion And Metastasis In Papillary Thyroid Carcinoma

Objective: To study the expression of MMP-2, TIMP-2, collagen type IV , and to understand their relationships with tumor invasion and lymph node metastasis in papillary thyroid carcinoma (PTC).Methods: In situ hybridization was used to detect MMP-2 and TIMP-2mRNA in PTC (n=95) and nearby no-tumorous tissues (n=59). The protein expression of MMP-2, TIMP-2 and collagen type IV in basement membrane was also studied with immunohistochemistry (SP methods).Results: 1. The positive expression rate of MMP-2mRNA and protein in PTC was 74.7%(71/95) and 77.9%(74/95), respectively; but in nearby no-tumorous tissues, it was only 10.2%(6/59) and 25.4%(15/59). The positive expression rate and intensity in PTC was much higher than that in nearby no-tumorous tissues (P<0.01,P<0.01). Moreover, the positive expression rate of MMP-2mRNA and protein was 59.3%(16/27) and 66.7%(18/27) in papillary microcarcinoma, 80.0%(40/50) and 80.0%(40/50) in intrathyroid carcinoma, and 83.3%(15/18) and 88.9%(16/18) in extrathyroid carcinoma, respectively; showing a rising tendency of positive rate with the advancing invasion. There were also significant differences of MMP-2mRNA and protein expression between PTC with lymph node metastasis [91.4%(32/35) and 97.1%(34/35)] and PTC without lymph node metastasis [65.0%(39/60) and 66.7%(40/60), P<0.01, P<0.01].2. On the contrast, the positive expression rate and intensity of TMP-2mRNA and protein were obviously higher in PTC [58.9%(56/95) and 64.2%(61/95)] than that in nearby no-tumorous tissues [20.3%(12/59) and 16.9%(10/59)]. Moreover, they were 70.4%(19/27) and 77.8%(21/27) in papillary microcarcinoma, 58.0%(29/50) and 62.0%(31/50) in intrathyroid carcinoma, 44.4%(8/18) and 50.0%(9/18) in extrathyroid carcinoma, respectively; showing a decreasing tendency of positive rate with the advancing invasion. There existed significant differences of TIMP-2mRNA and protein expression between PTC with lymph node metastasis [71.7%(43/60) and 73.3%(44/60), P<0.01, P<0.01].3. The positive expression rate of collagen type IV was lower in PTC [43.2% (41/95)] than that in nearby no-tumorous tissues [79.7%(47/59), P<0.01]. Moreover, it was 62.9%(17/27) in papillary microcarcinoma, 38.0%(19/50) in intrathyroid carcinoma, and 27.8%(5/18) in extrathyroid carcinoma, respectively; showing a decreasing tendency of positive rate with the advancing invasion. Significant differences of positive expression rate were found between PTC with lymph node metastasis [22.9%(8/35)j and PTC withoutlymph node metastasis [55.0%(33/60), P<0.05].4. The coexpression of collagen type IV and MMP-2 protein in 95 PTC was 21, negative expression of both was 1, the common consistency was 23.2%, and negatively correlated (r= -0.560, P<0.05).5. The coexpression of collagen type IV and TMP-2 protein in 95 PTC was 26, negative expression of both was 19, the common consistency was 47.4%,. but not correlated(P>0.05).Conclusions: 1. The mRNA and protein of MMP-2 in PTC is highly expressed, the positive expression has a rising tendency with the advancing invasion, indicating that (1) The overexpression of MMP-2 mRNA and protein is associated with the tumor invasion and biological behaviour. (2) The expression of MMP-2 mRNA and protein could be used as an important marker for early diagnosis and the prognosis.2.. The rate of detection of TIMP-2 mRNA and protein has a decreasing tendency with the advancing invasion, suggesting that the mRNA and protein of TIMP-2 is associated with the initiation and development in PTC.3. Collagen type IV in PTC is downexpressed , the positive expression siginificantly decreased with the advancing invasion of PTC. Collagen type IV has a negative relationship with MMP-2 protein , but not with TMP-2 protein . The loss of basement membrane collagen type IV is associated with the destroyed balance between MMP-2 and TIMP-2 protein.