Overexpress And Correlation Of PTTG And BFGF In Non-Small Cell Lung Cancer

Background and objectiveLung cancer is the leading cause of cancer-related mortality in both men and women, with 1.2 million new cases diagnosed every year and with 1 million deaths being recorded worldwide in 2001. Non-small cell lung cancer (NSCLC), accounts for approximately 80% of all lung cancers. The majority of NSCLC patients present with advanced disease at diagnosis and a large part of those diagnosed with early stage disease eventually recur, experiencing metastatic disease.Although chemotherapy has recently produced promising results as new adjuvant and adjuvant strategies for early-stage patients and some progress has been made in the treatment of locally-advanced and advanced disease and, treatment outcomes for NSCLC are still to be considered disappointing. Thus, clinical research of new treatments strategies is warranted.Pituitary tumor-transforming gene (PTTG) was isolated from rat growth hormone (GH4)-secreting pituitary cell lines by differential mRNA display (Pei,1997). It is overexpressed in many tumor cells, and possesses an important role in cell proliferation, transformation, apoptosis and signal transduction, is strongly correlated with tumorigenesis and development. PTTG facilitated the expression of c-myc and bFGF. As well, PTTG is closely related to bFGF and induces angiogenesis is through its regulation of various growth factors, such as bFGF.Angiogenesis is a fundamental event in the process of tumor growth and metastatic dissemination, and is strongly correlated with solid tumorigenesis, malignancy grades, metastasis and prognosis. bFGF is very important for the regulation of angiogenesis, the effect that bFGF promoted angiogenesis possibly participated in transformation of many tumors. Thus, molecular basis of tumor angiogenesis has been of keen interest in the field of cancer research, and the strategy of targeting angiogenesis has very recently achieved the first clinically significant results in the treatment of NSCLC. Explore the expression of PTTG and bFGF as well as their relations in NSCLC, so as provide theory basis for clinical diagnosis, forecast metastasis and biotherapy.Materials and mathodsLung cancerous tissues were collected from 61 patients of NSCLC from January 2001 to November 2005 in the First Affiliated hospital of Zhengzhou University. Among them 42 males and 19 females; of them, 36 squamous cancer cases, 25 adenocarcinoma cases;10 well-differentiated cases, 28 moderately-differentiated cases, 23 poorly-differentiated cases; and there are lymph node metastasis in 37 cases, and no lymph node metastasis in 24 cases; 20 normal lung tissues were collected as control. All the patients were not given any treatment including chemotherapy, radiotherapy and other treatments. All the tissues were fixed in 10% neutral formalin and embedded in paraffin. Strept Avidin-Biotin-enzyme Complex (SABC) immunohistochemical method is performed to detect the expression of PTTG and bFGF in lung cancerous tissues. The data are analyzed by software SPSS13.0 Chi-square and Fisher's exact probability method are used to compare the difference of PTTG and bFGF expression between groups. Spearman dependablity analyse is used to assess the correlation between PTTG and bFGF. P<0.05 is considered to be statistically significant.Results1. The positive staining of PTTG mainly located in cytoplasm, the expressive proportion of PTTG is 15.00% in normal lung tissues and 68.85% in lung cancerous tissues. A significant difference is observe between the two groups (P<0.05). In squamous cancer and adenocarcinoma, the expressive proportion of PTTG is 84.00% and 58.33% respectively. The difference between them is obviously (P<0.05). The well and the moderately-differentiated, the poorly-differentiated NSCLC groups are 57.89%, 86.95% respectively. In the group with and without lymph node metastasis, the rates are 81.08% and 50.00%. The relation between express of PTTG and clinical stage, the expressive proportion of PTTG in stageIII+IV(82.50%) is higher than in stage I +II(42.86%). The difference between them is significant (P<0.05). The results indicate the over expression of PTTG is related to pathological types, pathological grade, lymph node metastasis and TNM stage, and no related to age and sex in NSCLC.2. The positive staining of PTTG mainly located in cytoplasm of lung carcinoma cells, the expressive proportion of bFGF is 73.77% in cancerous tissues, which is significantly higher than in normal lung tissues (10.00%) (P<0.05). In squamous cancer and adenocarcinoma, the expressive proportion of bFGF is 72.22% and 76.00% respectively. The difference between them is no significant (P > 0.05). The well and the moderately-differentiated, the poorly-differentiated NSCLC groups are 63.16%, 91.30% respectively. The difference between them is significant (P<0.05). In the group with and without lymph node metastasis, the rates are 83.78% and 58.33%. The relation between express of bFGF and clinical stage, the expressive proportion of PTTG in stage III + IV (85.00%) is higher than in stage I + II (52.38%). The difference between them is obvious (P<0.05). The results indicate the over expression of PTTG is related to pathological grade, lymph node metastasis and TNM stage, and not related to pathological types, age and sex in NSCLC.Conclusion1. The expression of PTTG is low in normal lung tissues, but is obviously high in lung carcinoma; the expression of PTTG is closely related to pathological types, pathological grade, lymph node metastasis and TNM stage, and PTTG expression is more common in adenocarcinoma,which indicate that PTTG may be as a marker of tumor development and prognosis evaluation. 2. The expression of bFGF in NSCLC is signnificantly higher than in normal lung tissues, it is closely related to differentiatial grade, lymph node metastasis and TNM stage, but not related to pathological types, age and sex. Over-expression of bFGF may be closely correlated to invasion and angiogenesis, and may be serve as an important factor for the prognosis of the patients.3. Over-expression of PTTG and bFGF may be related to human NSCLC, PTTG over-expression may play an important role in the carcinogenesis and development in NSCLC by promoting the expression of bFGF protein,which may be involved in tumor angiogenesis. PTTG may be identified as a new carcinoma molecular marker and a therapeutic target.