The Relationships between Plasma MMP-9 and Invasion, Metastasis, Relapse of Laryngeal Carcinoma
|Course||Department of Otolaryngology - Head and Neck Surgery|
|Keywords||laryngeal carcinoma matrix metalloprotinases-9 MMP-9 relapse metastasis prognoses plasma|
Laryngeal carcinoma is a very common malignant tumor in Head and Neck, and the tissue type of the disease is chiefly laryngeal squamous cell carcinoma (LSCC). The morbidity of LSCC has been increasing gradually in China, especially in the northeast. The aggressive growth and metastasis are the two predominant and unfavorable factors that are to worsen prognosis of LSCC. It is TNM stage that has been used clinically and mainly to depict the propensity of LSCC to invade and disseminate now, with the most importance of the lymph node stage. The ratio of the occult lymph node metastases is very high in LSCC, especially the supraglottic carcinoma. But the occult lymph node metastases can not be diagnosed before the operation,so that limit the function of TNM stage on prognosis of LSCC. Therefore, a reliable marker is needed that can reflect the propensity of LSCC to invade and disseminate exactly, and can offer more precise information for therapy and prognosis of LSCC with TNM stage. On the other hand, because the local tissue appearance is changed after the operation of LSCC, the image can not reflect the relapse of LSCC timely, thus there is also to need a marker that can provide information timely for the relapse of LSCC in follow-up after the curative surgery.The invasion and metastasis of malignant tumor are the complex and sequential steps. Degradation of ECM is the key step to show the malignant behavior of tumor. Matrix metalloproteinase(sMMPs) is a family whose membranes can almost degrade all kinds of connective tissues. Therefore, It is thought to be an important tool for tumor to manifest its malignant behavior. Gelatinases are the important membranes of the family, including gelatinase A (MMP-2) and gelatinase B (MMP-9). They are not only degrade basic membrane (BM) likely the natural barrier that can prevent the malignant tumor from invading the normal tissue, but also take part in the tumor angiogenesis, especially gelatinase B. There were many researches in tissue level to conclude that expression of MMP-9 upgraded in LSCC than normal tissue, correlate with invasion and metastasis of LSCC, and can indicate the prognosis of LSCC. Recently, there were also studies to show that plasma MMP-9 significantly elevate in solid tumors, and have relationship with the malignant progression of tumor, and may be a biologic marker that can indicate the tumor prognoses and relapse in the follow-up. But there are few researches to investigate the usefulness of circulating MMP-9 in LSCC. There is no idea whether the level of circulating MMP-9 can reflect the characteristics and prognoses of LSCC.Objective: This study is not only to investigate the relationship of expression of MMP-9 with the clinic parameters of LSCC in tissue level, but also to emphasis on evaluating the usefulness of plasma MMP-9 in the invasion、metastases and relapse of LSCC. Meanwhile, the study also analysis’s the correlation of plasma MMP-9 with the MMP-9 immunoreactive staining in the corresponding tumor.Materials and methods :Materials:①Plasma samples of LSCC were observed from 40 patients who referred to the first affiliate Nan Chang university from July in 2006 to September in 2007.Meanwhile, there were the other 35 plasma samples observed ,including 15 plasma samples of relapsing laryngeal squamous cell carcinoma, 10 plasma samples of laryngeal squamous cell carcinoma without relapse, and 10 plasma samples from healthy people.②Tissue samples of 30 primary tumors out of 40 patients whose plasma samples were gathered were offered by our pathological division.Experiment methods:①The expression of MMP-9 was analyzed semi-quantitatively by immunohistochemical staining in the paraffin-embedded tissue samples.②The total MMP-9 in plasma (free and complex forms of MMP-9) was measured by ELISA.Results: 1. Positive expression of MMP-9 in the tissue of LSCC was 70%9(21/30). Expression of MMP-9 notably relate with T stages and Node stages(P=0.02,P=0.029), but do not with primary location of LSCC and pathological stages(P=0.066,P=0.458).2. There was a positive correlation between the level of plasma MMP-9 and the corresponding immunohistochemical staining of MMP-9(rs=0.524,P=0.003); The stage of immunohistochemical staining more intensive, the average level of plasma MMP-9 higher. The abundance of plasma MMP-9 maybe originates from the excessive expression of tissue MMP-9. 3. The average level of plasma MMP-9 in LSCC was obviously higher than the controls(P<0.001). 4. The level of plasma MMP-9 was statistically significantly correlated to the Node stage(P<0.001). The average level of plasma MMP-9 was 258.71±74.53ng/ml and high in the group of lymph node metastasis compared with the other group of which average level was 129.58±31.44ng/ml. But there were never any correlations between plasma MMP-9 and primary location of LSCC , pathological stage、T stage and age(P=0.859,P=0.948,P=0.301,P=0.541,respectively). 5. The concentration of MMP-9 was upgraded significantly in the patients with relapse after the operation of LSCC, compared with normal people and the patients who had never relapse after primary therapy(P<0.05,P<0.005, respectively). There was no statistically difference between normal people and the patients who had never relapse after primary therapy(P?0.05).Conclusions: 1.Compared with normal people, the level of plasma MMP-9 upgraded obviously in LSSC, and indicated whether there was lymph node metastasis. It may offer information for making a decision for operation of LSCC. 2. Because it is simple and without impairment to pick up blood sample, plasma MMP-9 may be a biological marker in the follow-up after the operation of LSCC. 3. There was a positive correlation between the level of plasma MMP-9 and the corresponding immunohistochemical staining of MMP-9, the abundance of plasma MMP-9 maybe originates from the excessive expression of tissue MMP-9.