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.

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As a first step toward making a guideline for the treatment of carcinoma of the lower gum, a questionnaire survey was conducted in order to identify the present status of the treatment in Japan. The results and controversial issues of 86 respondents are reported.
A total of 2986 cases of carcinoma of the lower gum were treated in the 86 institutions in the past 10 years (1993-2002) . T4 cases amounted to one-third of them (1016 cases) . As a T4 criterion, the level of mandibular canal criteria was accepted in 57 institutions (65.5% ) . On the other hand, only 34 institutions (39% ) accepted deep invasion into soft tissue as a T4 criterion together with mandibular invasion. Therefore, standardization of T4 criteria seems to be the first priority in making the guideline.
Tumor size, bone invasion and depth, and bone invasion pattern were regarded in almost all the institutions as one of the factors of indication of mandibulectomy (marginal and segmental resection) which is the most important issue in the treatment of carcinoma of the lower gum. However, the practical criteria of the indication for mandibulectomy vary considerably among the institutions. Thus, standardization of the criteria of the indication for mandibulectomy is a necessary but difficult task for making the guideline.

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