[Structural changes of tumor microenvironment in liver metastases of colorectal carcinoma].
The immunohistochemistry represents a very effective tool for describing the biological phenomena that characterize the primary or secondary neoplastic development. By using a complex immuno-morphologic approach, our study aims to develop a characterization of the metastatic liver microenvironment, based on the following features: similarities and differences in the proliferation activity, particular aspects of vascularity and immune response, the cellular dialogue generated at the level of the parenchyma - neoplastic tissue interface, the structure of the associated stroma.


METHODS
Ten cases of liver metastases have been studied, including five treated exclusively by surgery (group 1) and five with recurrent metastases occurred after a previous treatment by thermonecrosis (group 2). The cases were investigated by routine histopathological exam and by immunohistochemistry. The choice of the antibodies was motivated by the follow-up of the parameter classes presented below: (i) proliferation/apoptosis; (ii) structure; (iii) angiogenesis and lymphangiogenesis; (iv) immunological reactivity; (v) cytokines.


RESULTS
The elements defining the histopathologic and immunohistochemical patterns allowed a comparative evaluation of the metastasis models considered for the two groups of studied cases. The analysis of proliferation / apoptosis parameters proved a high aggressiveness in tumor proliferation for both types of metastases. Recurrent metastases showed an increased angiogenesis and a moderate lymphangiogenesis, as well as a massive matrix reshaping. The evaluation of the inflammatory infiltrate suggested that the development of the liver metastases is not accompanied by significant immunologic rejection, but it rather induces the tissue remodeling at the invasion border level. The recurrence corresponds to a typical interval of 6 months or longer, and is associated with intense fibrogenesis, angiogenesis, and inconsistent inflammatory infiltrate.


CONCLUSIONS
Therefore, the efficiency of the thermonecrosis procedure with water vapors seems to drastically depend on the complete necrosis of the target tumor, plus the adjacent cells of the parenchyma in a neighborhood of some millimeters. Moreover, the therapy must include anti-angiogenic resources as well as inflammation modulators, since the vascular supply and the leukocytic activity support the metastasis development.
Giuşcă
Simona Eliza
SE
Spitalul Clinic Judeţean de Urgenţa Universitar Sf. Spiridon" Iaşi, Clinica Chirurgie I.
Carasevici
E
E
Eloae-Zugun
Fl
F
Târcoveanu
E
E
Căruntu
Irina Draga
ID
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000032:analysis / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000951:Antigens, Neoplasm / Q000032:analysis; D017209:Apoptosis / Q000276:immunology; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000032:analysis*; D017252:CD3 Complex / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D024141:Collagen Type IV / Q000032:analysis; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000276:immunology / Q000473:pathology* / Q000628:therapy; D004250:DNA Topoisomerases, Type II / Q000032:analysis; D004268:DNA-Binding Proteins / Q000032:analysis; D006498:Hepatectomy; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000737:chemistry / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D009389:Neovascularization, Pathologic / Q000276:immunology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D051028:bcl-2-Associated X Protein / Q000032:analysis; D000097382:CD68 Molecule
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000951:Antigens, Neoplasm; D000068258:Bevacizumab; D014408:Biomarkers, Tumor; D017252:CD3 Complex; D024141:Collagen Type IV; D004250:DNA Topoisomerases, Type II; D004268:DNA-Binding Proteins; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; D051028:bcl-2-Associated X Protein; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C500987:monoclonal antibody D2-40