In our previous study we identified the presence of sVCAM-1 in ovarian cancer patient serum and its correlation with ascites sVCAM-1 concentration. These findings further supported the idea that sVCAM-1 is measurable in serum of advanced ovarian cancer serum and reflects the ongoing ovarian cancer. In the current study, we find that there was higher pretreatment serum sVCAM-1 in patients with early tumour progress or relapse when compared with patients relapsing 12 months after the treatment.
VCAM-1 is a member of Ig superfamily expressed on activated endothelial and mesothelial cells. VCAM-1 expression and tumour presence association has been evidenced. 6,7 It has been proposed as a prognostic tumour factor in different cancers, its value being its expression of different outcome. Increased serum sVCAM-1 levels have been linked to poor survival in relation to melanoma, Hodgkin and non- Hodgkin lymphoma and breast and gastric cancer. Similar results were seen in terms of colorectal cancer.8 In terms of renal cell carcinoma, VCAM-1 tumour cell expression is associated with better survival rate. 9
In the first study measuring sVCAM-1 serum concentrations in 15 patients with ovarian cancer it has been found that the concentration is significantly higher if patients have ovarian cancer. 14 The opposite is presented in another study, which reported lower sVCAM-1 concentration in patients with ovarian cancer compared to those with benign ovarian conditions. The likely cause of the difference may lie in patient selection, that is the one of the studies only patients with early ovarian cancer were included.16 Slack Davis and al. measured serum sVCAM-1 levels in ovarian cancer patient serum and state that this protein is linked to worse outcomes, whilst another recent study didn’t report any correlation between sVCAM-1 and ovarian cancer outcome, but only with metastasis presence. 5,10
In 2013 Scalici and al. suggested VCAM-1 as indicator for ovarian cancer response to platinum based chemotherapy, 11 and in a recent study, correlated serum sVCAM- 1 with mesothelial VCAM-1 expression in 18 patients with ovarian cancer and were unable to identify serum sVCAM-1 as a surrogate for mesothelium expression. 12 To the best of our knowledge we didn’t find any studies concerning sVCAM-1 and ovarian cancer recurrence. The role VCAM-1 in ovarian cancer is largely unclear, but it has been shown that mesothelial expression mediates tumor cell invasion. 13 In this study we measured increased levels of sVCAM-1 before operation in patients with ovarian cancer whose disease had progressed or tumor had relapsed at a very early stage, 12 months, after treatment completion. The observed increase in serum sVCAM-1 concentration could be attributed to disease biology and behaviour, as we were not able to find any correlation with tumour stage, disease grade or histological type between groups; we therefore measured sVCAM-1 from ascites as a fluid representing the local tumour microenvironment. It is an ideal media for evaluation of collected tumor cells and soluble proteins. The results from our measurements of patient’s sVCAM-1 concentrations in ascites only evidences a correlation with serum sVCAM-1 levels in the group of patients with early relapse or disease progress, but not in the group with later disease relapse. Research carried out by Slack Davis et al. attests the importance of VCAM-1in the regulation of ovarian cancer cell mesothelial invasion and metastatic progression. A possible explanation for this might be that if the tumours are more aggressive, mesothelial invasion is stronger and peritoneum mesothelial cells around the attached tumour cells are more severly affected. Peritoneum breakdown leads to easier ascites outflow with sVCAM-1 into the blood, so correlation is visible; whilst in the other group, mesothelial cell affection is slowed down and ascites transfer into the blood is limited, so sVCAM-1 correlation is not visible. Patients from this group needs longer periods of time to relapse post treatment. We also found that most patients with early relapse and tumour progress were treated with neoadjuvant chemotherapy, while most patients from the group that relapsed more than 12 months posttreatment were treated with primary cytoreductive surgery. The decision for treatment was based on radiological and laparoscopic evaluation of resectability, which is the standard pretreatment procedure at our institution. From our findings, we can assume a preoperative concentration of serum sVCAM-1, which can be another indicator for tumor aggressiveness for predicting primary optimal citoreduction and cancer treatment response. Ovarian cancer and cancer mediator biology are not very clear. Kong in a recent review covers the role and relevance of sVCAM-1 in inflammation and cancer, and highlights the emerging potential of sVCAM-1 as a new therapeutic target in terms of immunological disorder in cancer. 14 It has been shown that sVCAM-1 is closely associated with the progression of various immunological disorders, inflammation-associated vascular adhesion and the transendothelial migration. It seems possible that inflammation around tumours can be a crucial process for the different tumour and host behavior, tumor cell shedding and consequently different sVCAM-1 concentrations.
The very small sample size is a limitation of this study that needs to be acknowledged. We are also well aware that other factors can influence sVCAM-1 concentration, but in our case, the exclusion criteria was the presence of a systemic disease, known to affect sVCAM-1expression, both groups possibly experiencing typical inflammatory responses characteristic of cancer. The small sample size restricted our ability to perform multivariate analysis and nullify other possible influence.
In correlating and evaluating serum and ascites sVCAM-1 concentration and correlation, we showed that cancer aggressiveness is reflected in the serum in terms of cancer cells secretom and probably determinate before the treatment is started. However further work needs to be done on bigger sample size to establish whether sVCAM-1 in serum can be used in clinical practice as an early indicator for treatment outcome.
Serum sVCAM-1 concentration at the time of diagnosis might be predictive for different biologic behavior and treatment resistance and associated with cancer progression or recurrence. This is the first study demonstrating that higher serum sVCAM-1 concentrations in ovarian cancer patients is connected to early tumour recurrence or disease progression. Serum sVCAM-1 can be a potential tumor marker for ovarian cancer follow-up.