1Vanda Téglási MD - 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
2 Tamás Dániel Csűry - Semmelweis University, Budapest
3 Katalin Dezső MD, PhD - 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
4 Sándor Paku PhD, DSc - 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
5 Lilla Reiniger MD, PhD - 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest
In our preliminary studies we identified the pericytes as collagen producing cells in brain metastases (BM) which plays a key role in the vascularization of the tumor tissue. The aim of this study was to determine the relationship between the formation of connective tissue, the growth pattern and the vascularization of BM.
Formalin-fixed paraffin embedded BM samples of colon, breast and lung cancers were selected. On serial sections H&E and picrosirius red stains, PDGFRβ, CD31 and HSP47 immunoreactions were performed. On digitalized slides we measured the relative length of the tumor frontline, the relative amount of peritumoral picrosirius red and the peri- and intratumoral PDGFRβ positive areas. We also examined the morphology of vessels and quantified the amount of vital tumor tissue.
According to the growth pattern two main groups could be identified: i) pushing-type (well-demarcated frontline), comprising mainly the colon and lung cancer BM, ii) papillary-type (frontline with invaginations), comprising mainly the breast cancer BM. The length of the tumor frontline showed statistically significant difference between the two groups. The amount of peritumoral PDGFRβ and picrosirius red positive areas were significantly elevated in the pushing-type metastases. In the pushing-type metastases the PDGFRβ/HSP47 positive pericyte layer doubled and collagen was deposited between these layers. The outer pericyte layer and the majority of the deposited collagen was detached from the vessels and accumulated at the surface of the tumor. In the papillary-type metastases this process took place predominantly intratumorally. The amount of collagen showed an increase towards the tumor center in the papillary-type metastases, however in the pushing-type metastases a peritumoral accumulation could be detected. The pushing-type metastases incorporate fewer vessels than the papillary-type metastases, which results in a lower amount of vital tumor tissue.
The production of tumor stroma and the vascularization in BM correlates with their growth pattern.
Doctoral School of Pathological Sciences