Search

Primary thymic B-cell lymphoma is clinically characterized by aleukemic, highly aggressive local growth, infrequent distant metastasis, and infrequent secondary lymph node involvement. VLA-1 to VLA-6 are cell surface molecules binding to matrix molecules such as collagen, fibronectin, epiligrin, and laminin. VLA-4 additionally binds to VCAM-1 and ICAM-2, thus mediating intercellular adhesion. Other molecules involved in cell/cell adhesion are LFA-1 (CD11a/CD18), Mac-1(CD11b/CD18) and their ligand ICAM-1 (CD54), p150,95 (CD11c/CD18), LFA-3 (CD58), CD44, and LECAM-1. Twenty-three tumors, together with normal lymphoid tissue, were immunohistochemically examined to investigate the expression pattern of these molecules in thymic B-cell lymphomas and in their putative normal counterparts, namely thymic medullary B cells. Thymic B-cell lymphomas consistently lacked VLA-1,-2,-3,-5,-6, and CD11b, expressed ICAM-1 in 21 of 23 cases but were heterogenous for VLA-4, LFA-1, CD11c, LFA-3, CD44, and LECAM-1. Presence of LFA-1 correlated with LFA-3 expression (P = 0.029). The receptor profile of thymic B-cell lymphoma was reminiscent of the expressional status of normal thymic medullary B cells in some aspects but deviated in others: Assuming that, in terms of differentiation, thymic B-cell lymphoma is related to the asteroid variant of thymic medullary B cells, a propensity to down-regulate/lose VLA-4, CD11a, CD44, and LECAM-1 would have to be supposed in conjunction with a tendency to overexpress ICAM-1 and LFA-3. Sclerosis as an inconsistent phenomenon in thymic B-cell lymphoma was absent in 8 of 23 tumors. Presence of sclerosis correlated with LECAM-1 expression of the tumor cells (P = 0.038). Recent studies suggest that a locally growing/aleukemic phenotype of a B-cell neoplasia might be determined by the phenotype VLAs-, LFA-1+, ICAM-1+, CD44-, and LECAM-1-. Our data corroborate this view.

'Very late antigen' (VLA) proteins are members of the integrin superfamily with cell-surface receptor function and are involved in the cell-cell matrix interaction. They are heterodimers with a common beta 1 chain and different alpha chains counted through VLA-1 to VLA-6. The VLA-2 complex (alpha 2/beta 1) was found to act as collagen receptor on platelets and the VLA-6 complex (alpha 6/beta 1) as laminin receptor. Using monoclonal antibodies and an indirect immunoperoxidase method, we investigated the expression of VLA-alpha 2, VLA-alpha 6, and VLA-beta 1 chains in 20 normal colonic mucosa samples, in 20 colonic adenomas, and in 96 carcinomas together with 10 accompanying liver metastases. All three proteins were expressed throughout the colonic epithelium, except for VLA-alpha 2, which was present in the cryptic gland but was absent on the mucosal surface in some cases. In general, adenomas were strongly positive for the VLA proteins but 3 of 20 cases showed focal VLA-alpha 2-negative areas. The carcinomas revealed considerable heterogeneity of VLA-alpha 2 expression; ie, 59 tumors were completely positive, 35 tumors revealed a focal loss of antigen, and 2 cases were negative. This reduced antigen expression was statistically associated with Dukes' stage C/D (P = 0.003). VLA-alpha 6 was expressed throughout in all tumors. VLA-beta 1 was found extensively expressed in 77 carcinomas, partially expressed in 17 carcinomas, and was absent in 2 carcinomas. As compared to their primary tumors, liver metastases showed roughly corresponding patterns of antigen expression. The down regulation/loss of VLA proteins in a subset of epithelial colon tumors might cause a disturbed cell-cell/cell-matrix interaction that might augment the invasive property of their cells.

Changes were examined in the expression of Class I and II major histocompatibility complex (MHC) antigens by autochthonous cells of the terminal ileum affected by Crohn's disease. The study was based on the analysis of transmural specimens from terminal ileum segments obtained in the course of ileocolectomy for colon cancer and Crohn's disease. Serial sections were immunostained using monoclonal antibodies directed against monomorphic determinants of HLA-A,B,C, DR, DP, DQ, and the invariant chain (Ii) associated with Class II molecules. Compared with the normal state, the only change in Class I antigen expression occurring in Crohn's disease was the induction of HLA-A,B,C antigens in lymphatic endothelium. Changes in Class II antigen expression were more substantial. Enhancement of HLA-DR expression was found in enterocytes; DR induction was observed in glial cells of the visceral nervous plexus and in venular and venous endothelium. HLA-DP and DQ antigens were induced in enterocytes, glial cells, and capillary and venular endothelium, although this induction was restricted to areas of moderate or high inflammatory activity. The tissue distribution of Ii closely resembled that of HLA-DR, although this association was not strict: on the one hand, arterial endothelium contained low amounts of Ii in the absence of DR antigens; on the other hand, glial cells expressed Class II molecules in the absence of Ii. The extent of local enhancement/induction of MHC antigens was positively correlated with the local density of the cellular infiltrate. These data suggest that altered MHC antigen expression by autochthonous structures might be mediated by factors released from the lymphohistiocytic infiltrate, which is itself attracted by an unknown signal. In conjunction with an unknown antigen, the enhanced expression of Class II antigens might trigger an autoaggressive immune response.

Non-neoplastic mammary gland, 20 benign tumors and 206 carcinomas of the breast were immunohistochemically examined for expression of HLA-A, -B, -C, HLA-DR, -DP, and -DQ molecules and the HLA-D associated invariant chain (Ii). In contrast to cells from benign lesions, tumor cells of 51.2% of carcinomas had an abnormally low content of HLA-A, -B, and -C determinants ranging from reduction of antigenic density per cell (28.8%) over an incomplete (15.6%) to complete loss of antigens (6.8%). Associated with lymphohistiocytic stromal infiltrates, HLA-D/Ii determinants were found to be induced in benign duct and acinar epithelium after the order Ii greater than or equal to HLA-DR greater than or equal to HLA-DP greater than or equal to HLA-DQ. These antigens were also expressed, mostly noncoordinately, in 55.5% of carcinomas, and in 98 cases according to the above order. In 28.6%, Ii expression clearly exceeded HLA-D antigen expression; conversely, 6.2% contained HLA-DR+/Ii- tumor cell subsets. In breast carcinoma, the association of reduced HLA-A, -B, and -C expression and a noninduction of HLA-DR was highly significant (P less than 0.0009), suggesting an abnormal signal acting down-regulating on the expression of both classes of antigens. Because the modality of HLA-A, -B, and -C and HLA-D/Ii expression correlated with neither tumor type nor grade, it might be an independent parameter.