Structural examination of tryptase- and chymase-positive mast cells in livers, containing metastases from gastrointestinal cancers

Human mast cells are categorized into mast cells positive only for tryptase (MCT) and mast cells positive for both tryptase and chymase (MCTC). The structural appearance of tryptase-, and chymase-positive mast cells in metastatic liver disease and the variations in MCT and MCTC numbers in accordance with the origin of the primary tumors have been described in the present study. Liver mast cells are analyzed immunocytochemically using tryptase and chymase and by quantitative morphometry in 30 patients with colorectal (n=15), gastric (n=8), and pancreatic (n=7) cancers and in 5 control livers. The numbers of MCT and MCTC are increased in the extratumoral liver tissue (mainly portal tracts) as compared to controls. The numbers of MCT and MCTC in and around metastases with moderate or high grade of differentiation are statistically significantly higher, as compared to those with low grades of differentiation. The numbers of MCTC are greater than that of MCT in the extratumoral liver tissue and in metastases themselves. Ultrastructurally, mast cells immunostained with tryptase and chymase have three types of granules: electron dense granules with darkly precipitated reaction product, electron lucent granules without reaction product and electron lucent granules with sparse reaction product (altered granules). Both types of mast cells have small and large in size granules, resembling the MCTC phenotype described earlier. Tryptase-positive mast cells have granules with discrete scrolls and particulate and beaded pattern. Chymase-positive mast cells have granules with finely granular or particulate material. Substance P (SP)- and vasointestinal polypeptide (VIP)-positive mast cells are not observed in livers with metastases. The present study suggests that liver mast cells are mainly from the MCTC type, and are accumulated in peritumoral and metastatic areas. They may play a role in the formation of tumor stroma, or in tumor immunology in liver metastases from various primary gastrointestinal cancers.