Marker-Defined Perivascular Cells Predict Prognosis and Response to Treatment

Experimental studies suggest that perivascular cells affect tumor growth, metastasis and treatment response. Characterization of perivascular cell in clinical samples, and analyses of impact on prognosis and response to treatment, is therefore warranted.

We have developed an integrated set of procedures for analyses of perivascular cells using IHC-stainings with one endothelial cell marker (CD34) and markers for perivascular cells (PDGFaR, PDGFbR, ASMA and desmin). Digital image-analyses are used to determine fraction of covered vessels, intensity of marker expression and heterogeneity of marker expression. Studies focus on breast, colorectal, ovarian and kidney cancer.

Comparative analyses identified striking differences between tumor types including a higher fraction of covered vessels, and higher abundance of PDGFbR positive perivascular cells, in colorectal cancers. In the case of ovarian cancer, perivascular status in matched primary tumors and metastases was compared. A large degree of dis-concordance of most vascular characteristics was detected.

Concerning prognostic relevance, significant associations was detected between high perivascular PDGFbR cells shorter survival in breast, kidney and ovarian cancer. These associations were also significant in multi-variate analyses. High heterogeneity in perivascular PDGFbR expression was also associated with shorter survival in ovarian and kidney cancer.

To analyze impact on response to treatment, groups of chemotherapy-treated or non-treated metastatic colorectal cancer were analyzed. Interestingly, this analysis demonstrated an association between low perivascular PDGFbR expression, particularly strong in the chemo therapy-treated group. This finding suggests novel links between perivascular PDGFbR status and chemo-treatment response. Additional analyses also identified an association between shorter survival and low perivascular PDGFbR expression in bevacizumab-treated patients.

Collectively these studies demonstrate clinically relevant variation in tumor perivascular cells, suggestion continued exploration of these cells as biomarkers and treatment targets.