Serum VEGF, MMP-7 and CYFRA 21-1 as predictive markers of lung metastases from colorectal cancer

Background: Colorectal cancer (CRC) is one of the most common malignancy and the most frequent cause of cancer-related death in Western countries. In patients with CRC, the presence of liver or lung metastases (LMs) seriously affects survival, and the early diagnosis and resection of LMs significantly improves the outcome. Unfortunately, the sensitivity of imaging studies in detecting LMs is low, because the onset of solitary pulmonary nodules is common during follow-up, the most part of them are not malignant. The aim of this study was to evaluate the accuracy of serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-7 and cyrokeratin-19 fragment (CYFRA 21-1) as predictive markers of LMs from CRC. Methods: We retrospectively reviewed the medical charts of 21 patients with a history of CRC who developed histologically confirmed solitary or multiple PMs. There were 13 (61.9%) men and 8 (38.1%) women, with an overall median age of 65 years (range 31-82 years). Controls were 24 age-matched patients with CRC in whom the presence of PMs was excluded using 18F-FDG PET. The receiver operating characteristic (ROC) curve was used to obtain the optimal threshold value (cutoff point) for each TM. Results: The optimal cutoff was set at 5 ng/mL, 7.5 ng/mL, 250 pg/mL, and 2.8 ng/mL for CEA, VEGF, MMP-7, and CYFRA 21-1, respectively. The sensibility, specificity, positive (PPV) and negative (NPV) predictive value, and accuracy are reported in the Table. The logistic regression analysis excluded CYFRA 21-1 from the model, and thus we calculated the results also considering the combination of CEA+VEGF+MMP-7. The area under the ROC curve (AUC) was 0.712 (95% CI: 0.432-0.802). Conclusions: The periodic assay of CEA+VEGF+MMP-7 together may help to suspect the presence of LMs, suggesting the need to anticipate further evaluations.