Clinical Study Of The Relationship Between Expression Of PTEN And MMP-2 In Hepatocellular Carcinoma

Background and objective:Hepatocellular carcinoma (HCC), as one of the most common malignant tumors with the incidence rate still rising in our country, remains a poor prognosis despite of the improvement of modern diagnostic and therapeutic modalities. To a great extent, it is because of intrahepatic invasiveness and distant metastasis, usually resulting in the difficulty of radical resection and leads to postoperative recurrence. Therefore, it is very necessary to find some novel tumor markers in order to accurately evaluate the possibility of metastasis and the prognosis.Just like other tumors, the development of HCC is a complex process involving many genes and factors. The phosphorylation level of protein tyrosine, precisely regulated by PTKs and PTPs, plays an important role in the cellular signal transduction and cell cycle progression. As many PTKs are encoded by pro-oncogenes, it has been postulated that some of PTPs may act as tumor suppressor genes for a long time. But this assumption is not testified until the discovery of PTEN tumor suppressor gene.Since characterized and cloned separately by Jing Li, Peter A. Steck and DaMing Li in 1997, PTEN has been found to be inactivated by point mutations or homozygous deletions in many malignant tumors such as glioblastoma, prostate carcinoma, breast carcinoma and Cowden's disease. It attracted much enthusiasm from scientists in different countries. Much work has been done on the relationship between PTEN gene and some tumors including endometrial carcinoma, glioblastoma, prostate carcinoma, breast carcinoma and melanoma and so on.As we know, HCCs are generally associated with abundant extracellular matrix (ECM), and about 80% of HCCs are encapsulated with fibrous connective tissues. In view of this, the degeneration of ECM is the key point in the procedure of invasion and metastasis of HCCs, where the matrix metalloproteinases(MMPs) play the leading role. Matrix metalloproteinases are a family of enzymes with the main function of degradation of the extracellular matrix. MMPs have been defined functionally as having the following characteristics:(1)They are proteinases that can degrade one or many components of the extracellular matrix; (2)There is a zinc ion at the active point and can be inhibited by chelating agents; (3)They are secreted in a latent form, and requiring activation for proteolytic activity; (4)They can be inhibited by tissue inhibitors of metalloproteinases (TIMPs); (5)They share common amino acid sequences. MMP-2 (gelatinase A) is the main matrix metalloproteinase in decomposing collagen IV in the matrix, and collagen IV not only exists in the ECM, but also is one of the most important components in the basement membrane.In order to study the role of PTEN and MMP-2 in the occurrence and development of hepatocellular carcinoma., we evaluate the expression of PTEN and MMP-2 in HCC and normal liver tissues, hoping to provide some theoretical basis for the evaluation of the diagnosis, treatment and prognosis of HCC.Materials and methods:(1)Tissue specimens used for this study were obtained from 17 normal and 61 HCC livers, which were resected surgically from 2004 to 2005 by the First and Second affiliated Hospital of Zhengzhou University. All the specimens were fixed by 10% neutral formalin resolution. and embedded in paraffin. (2)Immunohistochemical S-P method was used to detect the expression of PTEN and MMP-2 in HCC and normal liver tissues.(3)The data was analyzed by statistical software SPSS 13.0. x~2 text and spearman text were used to analyze the difference and relationship between different groups. P value <0.05 was considered as having statistically significant value.Results:(1). PTEN was mainly located in the cytoplasm. The positive expression rate of PTEN in HCC tissues was 63.9% (39/61), in contrast, the positive expression rate of PTEN in normal liver was 94.1 %. There was significant difference between HCC and normal liver (P<0.05).(2). The positive expression rate of PTEN in HCC was related to the progress of the tumor pathological differentiation and invasion (P<0.05), whereas that had no relationship with the age,sex,HBsAg,AFP levels and the diameter (P>0.05).(3). MMP-2 was mainly located in the cytoplasm. The positive expression rate of MMp-2 in HCC tissues was 47.5% (39/61), in contrast, the positive expression rate of MMP-2 in normal liver was 11.8%. There was significant difference between HCC and normal liver (P<0.05).(4). The positive expression rate of MMP-2 in HCC was related to the invasion (P<0.05), whereas that had no relationship with the age,sex,HBsAg,AFP levels,diameter and the tumor pathological differentiation (P>0.05).(5). The positive expression intensity of PTEN in HCC was remarkably weaker than that in normal liver tissues, while the expression intensity of MMP-2 was stronger in HCC than that in normal liver tissues. Moreover, there was a negative relationship between the expression of PTEN and that of MMP-2 (R=—0.599, P<0.05).Conclusions:(1). The low expression of PTEN in HCC tissues suggests that PTEN probably plays an important role in the origin and development of HCC and is related to the invasion and the tumor pathological differentiation. (2). The high expression of MMP-2 in HCC is related to the invasion, suggesting that may be a key index for reflecting the biological behavior and prognosis of HCC.(3). There is a negative relationship between the expression of PTEN and that of MMP-2 in HCC tissues.