Close association between tumour cells and vascular basement membrane in gastric cancers with liver metastasis. An immunohistochemical and electron microscopic study with special attention to extracellular matrices

Abstract

To investigate morphological features valuable in estimating the propensity of gastric cancer to metastasize to the liver, we examined the primary tumours from 49 surgically resected advanced gastric cancers (24 with liver metastasis) and 45 autopsy cases, 19 with liver metastasis. We paid special attention to extracellular matrices--connective tissue stroma and basement membrane (BM)--using immunohistochemistry and electron microscopy. Type IV collagen staining showed that in differentiated carcinomas neoplastic glands were occasionally located in close proximity to the BM of thin-walled tumour blood vessels in back-to-back fashion. In poorly differentiated lesions, tumour cells were also oriented toward the vascular BM in pseudorosette-like pattern. Type III collagen staining and electron microscopy showed that in such regions tumour cells, with continuous or discontinuous BM, were immediately adjacent to vascular BM with no connective tissue stroma in between. On occasion tumour cells were in direct contact with vascular BM. These close associations were often found in carcinomas with a medullary growth pattern, irrespective of the degree of histological differentiation. However, they were virtually never seen in their benign counterpart. Of the resected cases, all 24 with liver metastasis showed this association, whereas only 10 of 25 (40%) without liver metastasis did so (P less than 0.001). In the autopsied cases, a similar positive correlation was observed between liver metastasis and this association. Furthermore, the tumor cells showing this juxtaposition showed evidence of vascular invasion. These results suggest that the close association between tumour cells and vascular BM is specific to the malignant neoplasm, and may be related to liver metastasis. Immunohistochemistry can be a great help in estimating the probability of liver metastasis.