Expression Of Nm23-H1,bFGF And MVD Correlates With Clinic Significance In Laryngeal Squamous Cell Carcinoma

BackgroundThe laryngeal squamous carcinoma (LSCC) is a common malignant neoplasm in head and neck .Its incidence is 1.5 to 3.4 per 100 000 persons in some provinces of China and increasing incidence have been observed in recent years. For patients of definitive LSCC, through laryngectomy good therapeutic efficacy can be get; the overall 5-year survival rates after laryngectomy are 80%. For those patients with cervical lymph node metastasis, the overall 5-year survival rates after laryngectomy are 46.2%, even though through radical neck dissection and postoperation radiotherapy.The metastatic process about the tumor cells which is complicated consist of a series of steps and multi-gene synergies, one of the necessary step is the inactivation of metastasis suppressor gene and angiogenesis. nm23 - H₁ is a tumor metastasis suppressor gene which is more in-depth study, the low expression of nm23-H₁ protein is negatively correlated with metastasis and clinical prognosis in many malignant tumors. But there are some inverse reports clinically. The expression of nm23-H₁ protein is not correlated with metastasis and clinical prognosis in some tumors, even through the nm23-H1 protein high expression is found when tumor metastasis. These contrary conclusions indicate that it's not inadequate awareness for nm23-H₁ which is needed more in-depth study. basic fibroblast growth factor (bFGF) is one kind of basis protein which is first isolated from bovine pituitary. Its extensive distribution in the body is found in nerve tissue, bone, genital organs, glands, WBC and a variety of other tumor cells. It can stimulate cell proliferation, differentiation with the cell membrane receptor-binding, and angiogenesis is induced by the formation.ObjectiveTo investigate the expression of nm23-H1 bFGF and detection of MVD, and explore their clinicopathologic significance in LSCC.Materials and Methods57 cases of LSCC specimen were obtained from the department of pathology of the first affiliated hospital of Zhengzhou university from January 2003 to December 2004. There were 56 male and 1 female whose age were from 26 to 92 years old (mean: 59.2 years old), the median age is 58.2 years old. All accepted no therapy for the tumor before their surgery and were proved to be squamous cell carcinoma by pathology. Another 20 cases normal laryngeal mucous membrane or polyps of vocal cord were chosen as controls. According to UICC TNM classification standards and histopathological grading standards for a second revision of fourth program, there were 18 cases of phase I,8 cases of phase II, 24 cases of phase III, 7 cases of phase IV,and 33 cases of grade 1,20 cases of grade 2, 4 cases of grade 3.Immunohistochemical SP method was adopted to investigate the expression of nm23-H1 and bFGF in this study. The normal laryngeal mucous membrane or polyps of vocal cord were used as control group, the known positive tissues were used as positive comparisons and PBS instead of the first antibody was used as negative comparison. CD34 was used for microvascular staining.The data was analyzed through package of software of SPSS13.0, and a P value of less than 0.05 was considered statistically.Results1.There was no expression of nm23-H₁ in polyp of vocal cord and neighboring normal tissues. The positive expression rates of nm23-H₁ in LSCC with grade 1 and grade 2 3 were 69.7% 25.0%. There were significant differences between the positive rates of grade 1 and grade 2 3(P<0.05). The positive expression rates of nm23-H₁ in the tumor tissues in group of patients with metastasis to cervical lymph node(71.4%) were statistically higher than that in group without metastasis(18.2%).There were significant differences between them(P<0.05). There were no significant differences of nm23-H₁ protein expression between I—II phase and III- IV phase.2. The expression of bFGF was not related with the classification of pathology and clinical stage of LSCC (.P>0.05). The positive expression rates of nm23-H1 in laryngeal carcinoma with cervical lymph nodes metastasis and no cervical lymph nodes metastasis were 81.8% 45.7%.There were significant differences between them(P<0.05).3. There were no significant differences between different classification of pathology of MVD(P>0.05). The MVD of tumor in phase III+IV was higher than that of tumor in phase I + II (P<0.05 ) . The MVD of patients with cervical lymph nodes metastasis were higher than that of patients without cervical lymph nodes (P<0.05) .4. The MVD of the tissues with positive expression of nm23-H₁ protein were lower than that negative. There were significant differences between them (P<0.05). The MVD of the tissues with positive expression of bFGF protein were higher than that negative. There were significant differences between them (P<0.05). In the positive expression of bFGF of laryngeal carcinoma, the positive expression rates(38.2%) of nm23-H1 were lower than the negative expression rates (69.6%) ,which were a negative correlation (r=-0.478, P<0.05) .Conclusion1. The expression of nm23-H₁ protein in LSCC is related to the cervical lymph node metastasis and pathological grades. It's suggested that nm23-H₁ protein plays an important role in the metastasis of laryngeal carcinoma. The tumor cells enhance their metastasis potential along with the down degree of cell differentiation.2. The expression of bFGF protein in LSCC is related to the cervical lymph node metastasis significantly. It's suggested that bFGF protein can promote tumor metastasis by a stimulating angiogenesis.3. The MVD is not related to the histological differentiation, but it is related to TNM phase and lymph nodes metastasis in laryngeal carcinoma. It's suggested that MVD may be one of prognostic indictors of laryngeal carcinoma.4. The expression of nm23-H₁ protein is related to MVD significantly. It's suggested that the MVD of negative expression of nm23-H1 protein is significantly higher than that of positive expression, the higher metastasis potential of tumor cell clone the stronger angiogenesis.5. The expression of bFGF protein is related to MVD significantly. The MVD of positive expression of nm23-H₁ protein is significantly higher than that of negative expression. It's suggested that bFGF can promote angiogenesis.6. There are negative correlation between nm23-H₁ and bFGF. It's suggested that decreased expression of nm23-H₁ protein and increased expression of bFGF protein can enhance tumor metastasis co operationally.