Tumor cell migration into the lymph nodes is an important aspect of cancer, yet little is known about the processes involved. CCR7 has been shown to play an important role in tumor cell migration and lymph node metastasis. The aim of our study was to evaluate the expression of CCR7 in nonsmall cell lung cancers (NSCLCs). We investigated CCR7 expression in 71 patients with NSCLC who underwent curative tumor resection by means of reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry. CCR7 mRNA was expressed in 45 cases (63.3%). The CCR7 mRNA expression was significantly associated with lymph node metastasis, stage, lymphatic invasion, CCR7 protein and CXCR4 protein (p ‫؍‬ 0.0001 for lymph node metastasis; p < 0.0001 for stage; p ‫؍‬ 0.0454 for lymphatic invasion; p < 0.0001 for CCR7 protein; p ‫؍‬ 0.0013 for CXCR4 protein). Twenty-six (57.8%) of 45 cases with CCR7 mRNA expression in their cancer tissues were node-positive, whereas only 3 (11.5%) of 26 cases without CCR7 mRNA expression were node-positive. Furthermore, expression of CCR7 mRNA was shown to be an independent predictor of lymph node metastasis by multivariate analysis (p ‫؍‬ 0.0117). Our study demonstrates that CCR7 might be related to the development of lymph node metastasis in NSCLC. It has been reported that tumor cell migration and metastasis share many similarities with leukocyte trafficking, which is critically regulated by chemokines and their receptors. 1 Of 17 different chemokine receptors, the chemokine receptors CXCR4 and CCR7 are reported to be highly expressed in malignant breast tumors. 2 Our knowledge of the molecular determinants of lymph node metastasis is clearly limited, although a small number of gene products have been shown to increase lymph node metastasis. 3 Expression of the chemokine receptor gene, CCR7, has been reported to enhance murine malignant tumors to metastasize to regional lymph nodes, 4 and RT-PCR analysis indicates elevated levels of CCR7 expression and a correlation with lymph node metastasis in gastric cancer. 5 However, there are no previous reports studying the clinical significance of CCR7 in nonsmall cell lung cancer (NSCLC). Thus, we investigated CCR7 expression in a series of 71 cases of curatively resected NSCLC by means of RT-PCR and immunohistochemical assays to evaluate its clinical significance. We also determined whether expression of CCR7 mRNA correlates with immunohistochemical assay of CXCR4. MATERIAL AND METHODS Tissue specimensTumor tissue was collected from 71 patients with NSCLC who underwent curative surgery from 1992 to 1996 at the Department of Surgery, Teikyo University School of Medicine. Patients who died within 1 month after surgery and patients with a past history of another cancer were excluded from the study. Patients were also excluded if they had received neoadjuvant chemotherapy or radiotherapy. Freshly removed pulmonary cancer tissues for RNA extraction were immediately frozen in liquid nitrogen and stored at Ϫ80°; until further use. In 5 of the cases,...

BACKGROUND Angiogenesis in individuals with various solid tumors has provided useful information on tumor progression and prognosis, and many examples of mast cell (MC) accumulation coupled with angiogenesis can be found in the literature. METHODS Utilizing monoclonal antibodies for tryptase that are specific markers for MC and for the endothelial surface marker CD34, the authors quantified MC infiltration in 180 patients with pulmonary adenocarcinoma who underwent curative tumor resection, to investigate the relation between mast cell density (MCD) and microvessel density (MVD), clinicopathologic factors, and prognosis. RESULTS A significant association was found between MCD and MVD (P < 0.0001). The MC count was significantly related to tumor progression, involving N classification and stage (P = 0.0002 for N classification and P = 0.0015 for stage). A significant difference in the rate of patient survival was detected between patients whose tumors had an MCD defined as high and those whose tumors had an MCD defined as low (P < 0.0001). Multivariate analysis also showed that MCD was significantly related to survival (P = 0.0378). CONCLUSIONS These data indicate that MC infiltration may contribute to tumor angiogenesis and tumor progression, and that MCD is a useful prognostic marker in pulmonary adenocarcinoma. Cancer 2000;88:2686–92. © 2000 American Cancer Society.

These data indicate that natural killer infiltration may contribute to the regulation of tumor progression and that the natural killer cell count can serve as a useful prognostic marker in overall and stage I pulmonary adenocarcinoma.

The relation between tumor-associated macrophage (TAM) density and the density of microvessels was investigated in specimens from 113 patients with pulmonary adenocarcinoma, as was the influence of TAM density on prognosis. The rank correlation test revealed a significant relation between TAM density and microvessel density (y = 14.418 + 0.863x, r = 0.454, p > 0.0001). A significant difference in patient survival rate was detected between tumors with a TAM density defined as high and those with a TAM density defined as low (p < 0.01). Multivariate analysis also showed that TAM density was significantly related to survival (p < 0.05). These data indicate that TAM infiltration may contribute to tumor angiogenesis, and that TAM density is a useful prognostic marker in pulmonary adenocarcinoma.