Histopathological study of stromal desmoplasia and the expression of extracellular matrix protoelytic enzyme in oral squamous cell carcinoma

—Relation to the mode of cancer invasion—

Abstract

Although cancer invasion is accompanied by desmoplasia as a stromal reaction, it remains unknown whether it acts as the host defense reaction or the scaffold of cancer cell growth. In this study, we examined the average of intra-stromal collagen fiber content by percent (Ave.-CFC (%) ) using a semi-quantification method based on image analysis of Azan staining, and the immunohistological expression of epithelial basement membrane (type IV collagen) and four typical matrix metalloproteinases (MMPs) including MMP-1, MMP-2, MMP-9, MT1-MMP, which can degrade extracellular matrix (ECM) protein at the cancer invasion front. Biopsy specimens from 84 patients of oral squamous cell carcinoma were studied to determine the relation of these findings to the mode of cancer invasion. Although a degreasing tendency of Ave-CFC (%) was shown in grade 1 to 4C, a massive volume of collagen fiber was found in grade 4D. Moreover, immunolocalization of MMPs was classified into two types based on positive cells i.e., the cancer cell-positive type and both cancer cell- and fibroblast-positive type. Especially in grade 4C and 4D, the cancer cell-and fibroblast-positive type of MMP-2 or MT1-MMP was highly frequent. Type 1V collagen tended to lack conformity with the mode of invasion. Based on the above result, it is speculated that the ECM proteolytic mechanism shifts to the cancer-stroma interactive type from the cancer cell leading type, causing progressive degradation of existing collagen fibers in the stroma, while the specific invasion system causes that collagen fiber synthesis to accelerate the invasion in grade 4D cancer.