The Effects Of EGFR Expression On Angiogenesis And Cell Proliferation In NSCLC

Objective: Lung cancer is one of the most common malignant tumors with thehighest morbidity and mortality. The major type of lung cancer is non-small cell lungcancer (NSCLC). Traditionally, the main therapy to NSCLC is surgical resection withchemotherapy. Because of the side effects from the chemotherapy, recently, thepersonalized therapy including target therapy with molecular target drags has beenperformed clinically, according to the characteristics of each patient. Personalizedmolecular target therapy relies on the understanding for pathogenesis of the cancertreated. However, the carcinogenesis of the NSCLC is not understood clearly until now.As many malignancies, the development of the cancer is related to cell abnormalproliferation with some changes of proto-oncogenes and suppressors. On other hand,with the increase of tumor size, the cancer should have to develop an ability topromote angiogenesis in order to obtain nutrient and oxygen supports. Epidermalgrowth factor receptor (EGFR) is a transmembrane glycoprotein receptor belonging tothe erb2family, with tyrosine kinase activity. It plays an important role in thepromotion of cell proliferation. Recently, it was found that some patients with NSCLCbringing highly expressive EGFRs were benefited from EGFR-tyrosine kinase inhibitor(EGFR-TKI). These findings indicated that some of NSCLC were induced by theabnormalities of EGFR in its expression and structure. Vascular endothelial growthfactor (VEGF) is the strongest angiogenic factor. Some cancers could promote theangiogenesis by secretion of VEGF. Microvasscular density (MVD) refers to number ofmicrovessels in unit area, and it is commonly used to represent the angiogenic ability ofa cancer. CD34, which is transmembrane glycoprotein on vascular endothelia andhematopoietic stem cell surface, is often used as a marker of vascular endothelia.Generally, we get MVD according to calculation of the cells with positive CD34expression. Proliferating cell nuclear antigen (PCNA) as DNA polymerase accessory protein has been widely used as biomarker for cell proliferation. In this study weexamined the protein expressions of EGFR, VEGF, CD34and PCNA. Then wecalculated MVD according to CD34expression in NSCLC. The aim of study is toexplore the mechanism of NSCLC by analyzing the relationships among EGFRexpression, cell proliferation and angiogenesis of NSCLC, and particularly to judge theeffects of EGFR expression on cell proliferation and angiogenesis in NSCLC.Methods: A total68NSCLC specimens were selected from the second hospital ofDaLian medical university. All clinical data such as patients’ gender and age wererecorded. Moreover, the histological type, differentiation and lymph node metastasis ofthese cancers were examined. None of the patients with the cancer received eitherradiation therapy or chemotherapy before the surgical treatment. Protein expressions ofEGFR, VEGF, CD34and PCNA were detected by immunohistochemistry.Experimental data were processed by SPSS16.0statistical software.Results: The positive rate of EGFR protein expression was45.6%(31/68) inNSCLC examined. The positive rates of EGFR protein expression were48.7%(19/39)and41.4%(12/29) in male and female patients respectively (P>0.05). The positive rateswere51.9%（14/27）and41.5%(17/41) in smoker and non-smoker respectively (P>0.05).The positive rates were46.2%(12/26),45.5%(15/33) and44.4%(4/9) in squamous cellcarcinoma, adenocarcinoma and other types respectively (P>0.05). The positive rateswere50.0%(23/46) and36.4%(8/22) in the high－middle and low differentiationgroups respectively (P>0.05). The positive rates were51.4%(19/37) and38.7%(12/31)in groups with and without lymph node metastasis groups respectively (P>0.05).The positive rate of VEGF protein expression was72.1%(49/68) in NSCLCexamined. The positive rates of VEGF protein expression were69.2%(27/39) and75.9%(22/29) in male and female patients respectively (P>0.05). The positive rateswere55.6%（14/27）and82.9%(34/41) in smoker and non-smoker respectively(P>0.05).The positive rates were75.8%(20/26),76.9%(25/33) and44.4%(4/9) insquamous cell carcinoma, adenocarcinoma and other types respectively (P>0.05). Thepositive rates were58.7%(27/46) and100.0%(22/22) in the high－middle and lowdifferentiation groups respectively (P<0.05). The positive rates were73.0%(27/37) and71.0%(22/31) in groups with and without lymph node metastasis groups respectively(P>0.05).The positive rate of CD34protein expression was33.8%(23/68) in NSCLCexamined. The positive rates of CD34protein expression were33.3%(13/39) and 34.5%(10/29) in male and female patients respectively (P>0.05). The positive rateswere33.3%（9/27） and34.1%(14/41) in smoker and non-smoker respectively(P>0.05).The positive rates were26.9%(11/26),33.3%(7/33) and55.6%(4/9) insquamous cell carcinoma, adenocarcinoma and other types respectively (P>0.05). Thepositive rates were23.9%(11/46) and54.5%12/22) in the high－middle and lowdifferentiation groups respectively (P<0.05). The positive rates were16.2%(6/37) and54.8%(17/31) in groups with and without lymph node metastasis groups respectively(P>0.05).The positive rate of PCNA protein expression was83.8%(31/68) in NSCLCexamined. The positive rates of PCNA protein expression were74.4%(29/39) and96.6%(28/29) in male and female patients respectively (P>0.05). The positive rateswere77.8%（21/27）and87.8%(36/41) in smoker and non-smoker respectively(P>0.05).The positive rates were96.2%(25/26),72.7%(24/33) and88.9%(8/9) insquamous cell carcinoma, adenocarcinoma and other types respectively (P>0.05). Thepositive rates were76.1%(35/46) and100.0%(22/22) in the high－middle and lowdifferentiation groups respectively (P<0.05). The positive rates were83.8%(31/37) and83.7%(26/31) in groups with and without lymph node metastasis groups respectively(P>0.05).Conclution:1. The NSCLCs with low differentiation would easily express VEGF.(2)The NSCLCs with low differentiation would have stronger ability to promoteangiogenesis and cell proliferation.(3)There were no clear effects from EGFR expression on angiogenesis and cellproliferation in the NSCLCs.(4) It is difficult to judge the ability of a cancer to promote angiogenesis inNSCLCs by detecting expressions of VEGF itself.(5) Simultaneous detection of these protein expressions might be helpful for us toselect molecular target drug in treatment of NSCLCs.