The Predictive Value of Vascular Endothelial Growth Factor and Nm23 for the Diagnosis of Occult Metastasis in Non‐small Cell Lung Cancer

Abstract

We assessed the association of vascular endothelial growth factor (VEGF) and nm23 expression with occult micrometastasis in lung cancer. As destination sites for micrometastasis, we scrutinized lymph node (LN) and bone marrow (BM) specimens. For LN, 122 stage I patients who had received curative operations were studied. As regards BM, 203 patients in stage I-IV who underwent operations were registered. Immunohistochemical anti-cytokeratin staining was used to detect microdissemination of cancer cells. The VEGF and the nm23 expression at the primary sites were immunohistochemically studied in 285 cases in total. The percentages of the patients with microdissemination were 28.7% for LN and 42.4% for BM. The outcome for the patients with LN or BM microdissemination was significantly worse than that for patients without it. The increased VEGF and the decreased nm23 expression within primary tumors were significantly associated with LN and BM microdissemination. The results indicate possible value of using these biological markers to predict the risk of systemic micrometastasis in non-small cell lung cancer. Key words: VEGF -nm23 -Lung cancer -Micrometastasis -RecurrenceWe previously reported that vascularity within tumors might predict the risk of recurrence in lung cancer patients with curative resections in early stages.1, 2) In a study that focused on "recurrence" after the curative resection of the primary tumor, we highlighted a novel biological indicator for the neo-formation of vessels, the vascular endothelial growth factor (VEGF). We found that this marker was strongly associated with the event of recurrence in stage I patients. This implies that angiogenesis within tumors may be of importance for metastasis. Recently, it has been discovered that VEGF influences a wide spectrum of biological functions, such as the immune systems via inhibition of the maturation of dendritic cells, the migration of tumor cells, cancer cell invasion, malignant transformation, and tumor survivability. [3][4][5][6][7][8] Besides angiogenesis, these multiple roles of VEGF may pertain to the event of recurrence/ metastasis, as well as to the cancer development. The intent of this study was to assess the association of VEGF and nm23 expression with micrometastasis in non-small cell lung cancer, and also to inquire about their significance as predictors for occult metastasis. PATIENTS AND METHODSPatients For the assessment of nodal micrometastasis, 122 primary tumors and 2030 lymph nodes (LN) were obtained from primary lung cancer patients in stage I. The 78 men and 44 women with a mean age of 65.0±8.2 years (range, 46 to 84) underwent operations at Kanazawa University Hospital from 1988 to 1991. The pathological types were 77 adenocarcinomas, 37 squamous cell carcinomas, six adenosquamous carcinomas, one large cell carcinoma, and one mucoepidermoid carcinoma. According to TNM classification, 78 patients were T1N0M0 and 44 were T2N0M0. On the other hand, for the assessment of bone marrow micrometastasis, 203 lung cancer patients in...

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