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The Korean Journal of Pathology 2008;42(6): 358-364.
Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer.
Joon Seon Song, Jin Kyung Jung, Jong Chul Park, Dong Kwan Kim, Se Jin Jang
1Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea. jangsejin@amc.seoul.kr
2Department of Thoracic and Cardiovascular Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
ABSTRACT
BACKGROUND: Expression of CXCR4 chemokine receptor, initially described to be involved in the homing of lymphocytes in inflammatory tissue, on breast cancer cell lines is associated with the development of lung metastases. In the present study, we evaluated CXCR4 expression in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarray blocks were constructed from 408 formalin-fixed, paraffin-embedded NSCLC samples and analyzed via immunohistochemical staining. RESULTS: We observed CXCR4 expression in 214 (66.3%) of the 323 tumors with cytoplasmic or nuclear staining patterns. These tumors were then divided into 109 negative, 166 weak-positive and 48 strong-positive expression groups. Strong expression of CXCR4 correlated with NSCLC recurrence (p=0.047) and distant metastasis (p=0.035). However, lymph node metastasis (p=0.683) and locoregional recurrence (p=0.856) were not associated with CXCR4 expression. Interestingly, the median overall survival times relative to CXCR4 expression were 71 months in the CXCR4-negative group, 43 months in the weakly positive CXCR4 group and 23 months in the strongly positive CXCR4 group. Strongly positive CXCR4 staining was associated with significantly worse outcomes (p=0.005, log-rank test). CONCLUSIONS: Expression of CXCR4 was associated with distant NSCLC metastases and shorter survival times.
Key Words: Non-small cell lung carcinoma; CXCR4 receptors; Metastasis