Correlation between the expression abnormalities of E-cadherin-β-catenin complex and lymph node metastasis (LNM) in early gastric cancer

15105 Background: Therapy for early gastric cancer (GC) varies according to risk of LNM. When the possibility of LNM is very remote, the primary lesion can be resected by the minimally invasive endoscopic surgery only. Therefore, useful parameters predicting LNM are needed. E-cadherin, a component of the cell-cell junctional structure, is known to correlate with GC. In vitro, previous studies elucidated that disorders of cell-cell junction increased the potential of metastasis, and that phosphorylation of β-catenin by c-erbB-2 induced loss of membranous E-cadherin and β-catenin, resulting in junctional structure disorders. Here we evaluated significance of analysis of these molecules in LNM prediction in early GC. Methods: The clinicopathological features and immunohistochemical expressions of E-cadherin, β-catenin, and c-erbB-2 in the primary lesion were studied in 28 patients (LNM +ve group: 14, LNM1 -ve group: 14) selected from 272 patients who underwent radical surgery for early GC between April 2000 to March 2004 at our hospital. All the patients consented to use of their stomach tissues for the clinical study afterwards. Statistical analysis was performed by t-test or χ2 test. Results: The clinicopathological features showed no significant differences between both groups. Loss of the membranous E-cadherin was noticed in 12 (85%) of the 14 LNM +ve patients, and in 8 (57%) of the 14 LNM -ve patients (p=0.209). This result was more remarkable in the intestinal type GC as the corresponding figures were 83% (5 of 6 ) and 16% (1 of 6) (p=0.083), respectively. Loss of the membranous β-catenin also showed a remarkable similar trend in the intestinal type GC, and the corresponding figures were 100% (6 of 6) and 50% (3 of 6) (p=0.182), respectively. Two patients showed over-expression of c-erbB2 and nuclear accumulation of β-catenin, and both had intestinal type GC with LNM. Conclusions: These results suggested that the same molecular signal pathway - as in vitro - including E-cadherin, β-catenin, and c-erbB2 induced LNM in early GC (intestinal type). We concluded that analysis of the expressions of these molecules is useful for not only LNM prediction but also determination of the therapeutic modality especially in intestinal type early GC. No significant financial relationships to disclose.

Alpha v and alpha 3 integrin subunits are associated with myofibrils during myofibrillogenesis

The development of the myofibrillar apparatus in skeletal muscle is a process in which transmembrane linkages with adhesion molecules are implicated. Integrins are one class of transmembrane adhesion receptors which appear to mediate these interactions. Two prominent linkages are at the myotendinous junction (MTJ), which resides at the ends of the cell and connects myofibrils to the tendon, and the costameres, which encircle the girth of the cell and connect the Z-disks to the sarcolemma. In this study we report that the alpha v integrin subunit is a prominent component of the costamere. The alpha v subunit is present initially on developing myotubes in a diffuse staining pattern with some concentration along nascent myofibrils. However, it appears in a striated pattern at the costamere and inconsistently at the M-line following the striation of alpha-actinin and titin but before that of desmin. Its recruitment to preformed striation suggests that it is incorporated into a pre-existing structure. The presence of alpha v in the costamere points to a role in lateral myofibrillar anchorage. In addition, we find that the alpha 3 subunit is transiently associated with myofibrils along portions of their lengths and at their ends during myofibrillogenesis. The alpha 3 subunit staining shows a novel localization and junctional structure. As myofibrils become striated the alpha 3 integrin dissociates from the localized pattern and becomes diffuse. This suggests a possible role in the stabilization of nascent myofibrils prior to striation. Antibody-induced perturbation of adhesion mediated by the integrin beta 1 subunit in developing myotubes inhibits assembly of the sarcomeric architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha v and alpha 3 integrin subunits are associated with myofibrils during myofibrillogenesis

The development of the myofibrillar apparatus in skeletal muscle is a process in which transmembrane linkages with adhesion molecules are implicated. Integrins are one class of transmembrane adhesion receptors which appear to mediate these interactions. Two prominent linkages are at the myotendinous junction (MTJ), which residues at the ends of the cell and connects myofibrils to the tendon, and the costameres, which encircle the girth of the cell and connect the Z-disks to the sarcolemma. In this study we report that the alpha v integrin subunit is a prominent component of the costamere. The alpha v subunit is present initially on developing myotubes in a diffuse staining pattern with some concentration along nascent myofibrils. However, it appears in a striated pattern at the costamere and inconsistently at the M-line following the striation of alpha-actinin and titin but before that of desmin. Its recruitment to preformed striation suggests that it is incorporated into a pre-existing structure. The presence of alpha v in the costamere points to a role in lateral myofibrillar anchorage. In addition, we find that the alpha 3 subunit is transiently associated with myofibrils along portions of their lengths and at their ends during myofibrillogenesis. The alpha 3 subunit staining shows a novel localization and junctional structure. As myofibrils become striated the alpha 3 integrin dissociates from the localized pattern and becomes diffuse. This suggests a possible role in the stabilization of nascent myofibrils prior to striation. Antibody-induced perturbation of adhesion mediated by the integrin beta 1 subunit in developing myotubes inhibits assembly of the sarcomeric architecture.(ABSTRACT TRUNCATED AT 250 WORDS)

The expression of desmosomal and corneodesmosomal antigens shows specific variations during the terminal differentiation of epidermis and hair follicle epithelia.

Using five monoclonal antibodies (MAb), we studied by indirect immunofluorescence the desmosomes and a junctional structure specific to cornified layers, the corneodesmosome, in normal and plantar epidermis and in the various sheaths of the anagen hair follicle. The monoclonal antibodies DP1&2.2-15, PG5.1, and DG3.10, specific for desmoplakins I/II, plakoglobin, and desmoglein I, respectively, were used to study the desmosome antigens, and G36-19 and G20-21 to study the corneodesmosome antigens. The distribution and sequence of expression of the five antigens allowed the nine epithelial differentiation pathways studied to be merged into four distinct families: non-plantar epidermis, characterized by the absence of desmosome and corneodesmosome antigens in the stratum corneum; the outer root sheath of the hair follicle, which behaves like the viable layers of the epidermis with regard to the desmosome antigens but does not express the corneodesmosome antigens; plantar epidermis and the three components of the inner root sheath in which the corneodesmosome antigens are present up to the desquamating layer; and the three components of the hair shaft, which are characterized by the absence of expression of both the desmosome and the corneodesmosome antigens in its mature portion.

Isolation, characterization, and localization of the spanning protein from skeletal muscle triads.

A monoclonal antibody has been developed against the putative junctional protein or spanning protein (SP) from skeletal muscle triads. By immuno-affinity chromatography, we have purified this protein. The native protein has a molecular mass of 630-800 kD, as determined by gel filtration and rate zonal centrifugation. Within the limits of the methods used, the basic unit of the SP appears to be a dimer. In electron micrographs, it is shown to exhibit a circular profile with a diameter of approximately 100 A. In thin section analysis, the protein is frequently observed as parallel tracks of electron-dense particles bordering a translucent core. We suggest that the basic unit of the junctional structure is a dimer of 300-kD subunits and that four such entities constitute the intact SP. The purified protein has been used to develop polyclonal antibodies. By immunoelectron microscopy using immunogold probes, the SP has been localized to the junctional gap of the triad. By attaching the SP to an affinity resin, three proteins have been identified as forming associations with the SP. The Mrs of the proteins are 150, 62, and 38 kD; the 62-kD protein is calsequestrin.