Wojciech Laudański

Serum tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A) are associated with prognosis in esophageal cancer patients

PURPOSE The matrix metalloproteinases, tissue inhibitors of metalloproteinases and angiogenesis contribute to growth and spread of cancer. We investigated the correlation between pretreatment serum levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A), and clinicopathologic features and survival in patients with esophageal cancer (EC). MATERIAL/METHODS Serum TIMP-1 and VEGF-A were measured by enzyme-linked immunosorbent assay (ELISA) in 89 patients with EC, and 30 healthy controls. RESULTS Serum TIMP-1 and VEGF-A levels were significantly higher in patients with esophageal carcinoma than in the control group (p=0.001 and p<0.001, respectively). High levels of TIMP-1 were associated with histological type (p<0.001), tumor depth (p<0.001), stage (p<0.001) and lymph node metastases (p=0.001). Subgroup analysis showed that tumor size (p<0.001), tumor depth (p<0.001), stage (p<0.001), lymph node metastases (p=0.002), distant metastases (p=0.009) and resectability (p=0.003), were correlated with an elevated level of VEGF-A. Patients with elevated levels of TIMP-1 and VEGF-A had a significantly lower overall survival (p=0.02 and p=0.048, respectively), and disease-free survival (TIMP-1, p<0.001). CONCLUSION High serum levels of TIMP-1 and VEGF-A were found to be associated with tumor progression and unfavorable prognosis in patients with EC.

Lymphatics-associated genes are downregulated at transcription level in non-small cell lung cancer

The present study aimed to verify a possibility of ongoing lymphangiogenesis in non-small cell lung cancer (NSCLC) via examination of mRNA levels of a number of lymphangiogenesis-associated genes in tumors. It was hypothesized that transcriptional activation of these genes would occur in tumors that stimulate new lymphatic vessel formation. The study was performed on 140 pairs of fresh-frozen surgical specimens of cancer and unaffected lung tissues derived from NSCLC stage I-IIIA patients. mRNA levels were evaluated with the reverse transcription-quantitative polymerase chain reaction method and expressed as fold change differences between the tumor and normal tissues. Possible associations between expression and patient clinicopathological characteristics and survival were analyzed. In the NSCLC tissue samples, vascular endothelial growth factor (VEGF) C, VEGFD, VEGFR3, VEGFR2, VEGFR1, lymphatic vessel endothelial hyaluronan receptor 1, integrin subunit α 9, FOX2, neuropilin 2, fibroblast growth factor 2 genes were significantly downregulated (P<0.001 for all) compared with matched normal lung tissues, whereas mRNA levels for VEGFA, spleen associated tyrosine kinase, podoplanin, and prospero homeobox 1 genes were similar in both tissues. Neither lymph node status, nor disease pathological stage influenced expression, whereas more profound suppression of gene activities appeared to occur in squamous cell carcinomas compared with adenocarcinomas. The VEGFR1 mRNA expression level was significantly connected with patient survival in the univariate analysis, and was an independent prognostic factor for overall survival in the multivariate Coxs proportional hazards model (HR 2.103; 95% confidence interval: 1.005-4.401; P=0.049). The results support a hypothesis of absence of new lymphatic vessel formation inside growing NSCLC tumor mass, however do not exclude a possibility of lymphangiogenesis in narrow marginal tumor parts.