Clinical Study of Vascular Endothelial Growth Factor-C and Cytokeratin 19 in StageⅠNon-small Cell Lung Cancer Patients_Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Authors：

WANG Yaopeng , WANG Mingzhao , LUO Yiren , WEI Zhaoxia , XUAN Yunpeng.

Department of Thoracic Surgery，Affiliated Hospital of Qingdao University Medical College，Qingdao 266003，Shandong， P. R. China;

Corresponding author：

Keywords：

Non-small cell lung cancer; 　Vascular endothelial growth factor-C; 　Cytokeratin 19

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Abstract:　Objective　To evaluate the significance of expression of vascular endothelial growth factor-C （VEGF-C）　and cytokeratin 19 （CK19） in patients with stage I non-small cell lung cancer （NSCLC）.　Methods　A total of 269　patients with NSCLC who underwent standard lobectomy and lymph node dissection by the same surgical team in our hospital from January 2004 to June 2005 were included in this study. All the clinical data and follow-up results were complete, and all the pathological specimens were well kept. No preoperative or postoperative adjuvant therapy such as radiotherapy and chemotherapy was administered to those patients. Expressions of VEGF-C in cancer tissues was detected by immunohistochemical streptavidin-peroxidase （S-P） method, and CK19 was marked to examine micrometastasis in hilar and mediastinal lymph nodes. Clinical outcomes, pathological results and follow-up data were analyzed in combination with VEGF-C and CK19 expression.　Results　VEGF-C expression was not statistically different between different category in sex（Hc=1.722，P=0.084）, age （Hc=0.914，P=0.360）, smoking （Hc=2.440，P=0.295）, pathology type （Hc=5.668，P=0.058）or tumor size （Hc=0.165，P=0.920） . VEGF-C expression was statistically different between different groups of pathological differentiation （Hc=29.178，P=0.000). CK19 expression was not　statistically different between different category in sex（χ2=0.000，P=0.999）, age （χ2=0.005，P=0.999）, smoking （χ2=2.294，P=0.317）, pathology type （χ2=0.573，P=0.289）, tumor size（χ2=0.006，P=0.999）, and pathological differentiation （χ2=2.927，P=0.231）. Five-year survival rate was statistically different between different grade of VEGF-C expression （χ2=37.318，P=0.000), and was also statistically different between positive group and negative group of CK19 （χ2=39.987，P=0.000). There was statistical difference between different grade of VEGF-C expression and positive rate of CK19 （χ2=25.954，P=0.000).　Conclusion　Expression of VEGF-C and CK19 is closely related to postoperative 5-year survival of patients with stage I NSCLC. Detection of VEGF-C and　CK19 is of great clinical significance as it is helpful to predict patient prognosis and choose proper postoperative adjuvant therapy.

Citation： WANG Yaopeng,WANG Mingzhao,LUO Yiren,WEI Zhaoxia,XUAN Yunpeng.. Clinical Study of Vascular Endothelial Growth Factor-C and Cytokeratin 19 in StageⅠNon-small Cell Lung Cancer Patients. Chinese Journal of Clinical Thoracic and Cardiovascular Surgery, 2012, 19(4): 385-389. doi: Copy

1.	endothelial growth factors C and D correlates with lymphangiogenesis and lymph node metastasis in lung adenocarcinoma. Thorac Cardiovasc Surg， 2009， 57 （5）：291-294.
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12.	童向东，曲家骐，李敬龙. CK在Ⅰ期非小细胞肺癌患者淋巴结中的表达及其临床意义. 中国胸心血管外科临床杂志， 2007， 14 （5）：345-349．.
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14.	Kalomenidis I， Dimakou K， Kolintza A， et al. Sputum carcinoembryonic antigen， neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis. Respirology， 2004， 9 （1）：54-59.
15.	Saintigny P， Coulon S， Kambouchner M， et al. Real-time RT-PCR　detection of CK19， CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma. Int J　Cancer， 2005， 115 （5）：777-782.
16.	郑智，潘铁成，李军，等. CK-19抗体在检测非小细胞肺癌淋巴结微转移中的应用. 华中科技大学学报（医学版）， 2004， 10 （5）：606-608， 618．.
17.	Das S， Ladell DS， Podgrabinska S， et al. Vascular endothelial growth factor-C induces lymphangitic carcinomatosis， an extremely aggressive form of lung metastases. Cancer Res， 2010， 70 （5）：1814-1824.
18.	Bo C， Xiaopeng D， Chuanliang P， et al. Expression of vascular.
19.	王耀鹏，朱晓峰，王洲. 血管内皮生长因子-C过度表达与临床Ⅰ期非小细胞肺癌淋巴结转移的相关性. 第三军医大学学报， 2010， 32 （10）：1109-1111.

1. endothelial growth factors C and D correlates with lymphangiogenesis and lymph node metastasis in lung adenocarcinoma. Thorac Cardiovasc Surg， 2009， 57 （5）：291-294.
2. 　Groome PA， Bolejack V， Crowley JJ， et al. The iaslc lung Cancer Staging Project:validation of the proposals for revision of the T， N， and M　descriptors and consequent stage groupings in the forthcoming（seventh）edition of the TNM classification of malignant tumors. J Thorac Oncol， 2007， 2 （8）：694-705.
3. 　Goldstraw P， Crowley J， Chansky K， et al. The iaslc lung cancer staging project：proposals for the revision of the TNM stage groupings in the forthcoming （seventh） edition of the TNM classification of malignant tumours. J Thorac Oncol， 2007， 2 （8）：706-714.
4. 　Ko YH， Jung CK， MA LE， et al. Clinical significance of vascular endothelial growth factors （VEGF）-C and-D in resected non-small cell lung cancer. Cancer Res Treat， 2008， 40 （3）：133-140.
5. 　Karpanen T， Egeblad M， Karkkainen MJ， et al. Vascular endothelial growth factor C promotes tumor lymphangiogenesis and intralymphatic tumor growth. Cancer Res， 2001， 61 （5）：1786-1790.
6. 　王艳，朱波，叶明福，等. 非小细胞肺癌VEGF-C表达与淋巴管生成和淋巴转移关系的研究. 中国肺癌杂志， 2006， 4 （2）：182-186．.
7. 　Wang J， Zhang B， Guo Y， et al. Artemisinin inhibits tumor lymphangiogenesis by suppression of vascular endothelial growth factor C. Pharmacology， 2008， 82 （2）：148-155.
8. 　Liu H， Yang Y， Xiao J， et al. Inhibition of cyclooxygenase-2 suppresses lymph node metastasis via VEGF-C. Anat Rec （Hoboken）， 2009， 292 （10）：1577-1583.
9. 　Shibata MA， Morimoto J， Shibata E， et al. Combination therapy with short interfering RNA vectors against VEGF-C and VEGF-A suppresses lymph node and lung metastasis in a mouse immunocompetent mammary cancer model. Cancer Gene Ther， 2008， 15 （12）：776-786.
10. 　Chen X， Xie Q， Cheng X， et al. Role of interleukin-17 in lymphangiogenesis in non-small-cell lung cancer：enhanced production of vascular endothelial growth factor C in non-small-cell lung carcinoma cells. Cancer Sci， 2010， 101 （11）：2384-2390.
11. 　Gusterson B. Are micrometastases clinically relevant? Br J Hosp med， 1992， 47 （4）：247-248.
12. 　童向东，曲家骐，李敬龙. CK在Ⅰ期非小细胞肺癌患者淋巴结中的表达及其临床意义. 中国胸心血管外科临床杂志， 2007， 14 （5）：345-349．.
13. 　Coulombe PA. The cellular and molecular biology of keratins：　beginning a new era. Curr Opin Cell Biol， 1993， 5 （1）：17-29.
14. 　Kalomenidis I， Dimakou K， Kolintza A， et al. Sputum carcinoembryonic antigen， neuron-specific enolase and cytokeratin fragment 19 levels in lung cancer diagnosis. Respirology， 2004， 9 （1）：54-59.
15. 　Saintigny P， Coulon S， Kambouchner M， et al. Real-time RT-PCR　detection of CK19， CK7 and MUC1 mRNA for diagnosis of lymph node micrometastases in non small cell lung carcinoma. Int J　Cancer， 2005， 115 （5）：777-782.
16. 　郑智，潘铁成，李军，等. CK-19抗体在检测非小细胞肺癌淋巴结微转移中的应用. 华中科技大学学报（医学版）， 2004， 10 （5）：606-608， 618．.
17. 　Das S， Ladell DS， Podgrabinska S， et al. Vascular endothelial growth factor-C induces lymphangitic carcinomatosis， an extremely aggressive form of lung metastases. Cancer Res， 2010， 70 （5）：1814-1824.
18. 　Bo C， Xiaopeng D， Chuanliang P， et al. Expression of vascular.
19. 　王耀鹏，朱晓峰，王洲. 血管内皮生长因子-C过度表达与临床Ⅰ期非小细胞肺癌淋巴结转移的相关性. 第三军医大学学报， 2010， 32 （10）：1109-1111.

Chinese Journal of Clinical Thoracic and Cardiovascular Surgery

Clinical Study of Vascular Endothelial Growth Factor-C and Cytokeratin 19 in StageⅠNon-small Cell Lung Cancer Patients

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