caa a22 4500 397562470 CHVBK 20180308164819.0 cr unu---uuuuu 161202e19960403xx s 000 0 eng 10.1093/jnci/88.7.442 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.7.442 Changes in Integrin and E-Cadherin Expression in Neoplastic Versus Normal Thyroid Tissue [Elektronische Daten] [Guido Serini, Livio Trusolino, Enrico Saggiorato, Ottavio Cremona, Marco De Rossi, Alberto Angeli, Fabio Orlandi, Pier Carlo Marchisio] Background The functional organization of polarized epithelia depends mostly on adhesion molecules belonging to the integrin and cadherin families. These molecules either recognize basement membrane components, such as laminins, or form intercellular junctions via homotypic interactions. Such tissue organization is often disrupted upon neoplastic transformation, and the resulting loss of functional polarization and cell cohesion might be a prerequisite for the invasive and metastatic behavior of carcinomas. Purpose We studied modifications of thyroid adhesive mechanisms at various stages of neoplastic progression in terms of adhesion molecule expression, topography, and functional regulation by tyrosine kinases. Starting from this working hypothesis, we sought to identify one or more biological markers that would be suggestive of malignant transformation and poorer prognosis and that could be developed as a reliable indicator(s) in early diagnostic steps. Methods The study was carried out on both surgical samples and the corresponding fine-needle aspiration biopsy smears (numbers of specimens collected: 19 adenomas, seven follicular carcinomas, 13 papillary carcinomas, and 39 normal tissues). Immunohistochemistry of tissue sections and smears and immunoprecipitation and western blot analysis of protein extracts were done with a battery of monoclonal and polyclonal antibodies. Northern blotting was performed on RNA extracts from frozen tissue samples and use of an intergrin subunit β4 complementary DNA probe. Results Our findings can be summarized as follows: 1) In normal thyroid cells, the cooperative role of integrin α6β4 and laminin 5/kalinin in hemidesmosome-mediated adhesion is missing, and recognition of the basal lamina occurs via integrin α3β1 and laminin 1 and/or 2 (this pattern being maintained in adenomas but altered in carcinomas regardless of their histotype or differentiation grade); 2) only in carcinomas with clinical and/or histologic aggressiveness do neoexpression of integrin subunit β4 and loss of laminin 2/merosin occur, indicating denovo assembly of integrin α6β4; 3) pericellular redistribution and cytoskeletal disconnection of the E-cadherin-catenin complex occur; and 4) basal E-cadherin tyrosine phosphorylation decreases in carcinomas as compared with that in normal and adenomatous tissues. Conclusions The malignant progression of thyroid tumors involves marked rearrangements of cell-basement membrane and cell—cell adhesion molecules and changes in their cytoskeleton linkage. These rearrangements are also easily and reproducibly detected on fine-needle aspiration biopsy smears. Implications Immunodetection of adhesion molecules in sections and/or fine-needle smears may complement the toolbox of thyroid surgical pathologists; it may expand the possibilities of achieving a correct early diagnosis of thyroid tumors and of gaining some prognostic information on thyroid tumors. [J Natl Cancer Inst 1996;88:442-9] © Oxford University Press REPORTS nationallicence Serini Guido Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut Trusolino Livio Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut Saggiorato Enrico Department of Clinical and Biological Sciences, University of Torino Novara Branch aut Cremona Ottavio Department of Biomedical Sciences and Human Oncology, University of Torino, and Department of Medical Sciences, University of Torino Novara Branch aut De Rossi Marco Department of Biological and Technological Research, San Raffaele Scientific Institute. aut Angeli Alberto Department of Clinical and Biological Sciences, University of Torino Novara Branch aut Orlandi Fabio Department of Clinical and Biological Sciences, University of Torino Novara Branch aut Marchisio Pier Carlo Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/7(1996-04-03), 442-449 0027-8874 88:7<442 1996 88 jnci https://doi.org/10.1093/jnci/88.7.442 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.7.442 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Serini Guido Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut NATIONALLICENCE 700 1- Trusolino Livio Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut NATIONALLICENCE 700 1- Saggiorato Enrico Department of Clinical and Biological Sciences, University of Torino Novara Branch aut NATIONALLICENCE 700 1- Cremona Ottavio Department of Biomedical Sciences and Human Oncology, University of Torino, and Department of Medical Sciences, University of Torino Novara Branch aut NATIONALLICENCE 700 1- De Rossi Marco Department of Biological and Technological Research, San Raffaele Scientific Institute aut NATIONALLICENCE 700 1- Angeli Alberto Department of Clinical and Biological Sciences, University of Torino Novara Branch aut NATIONALLICENCE 700 1- Orlandi Fabio Department of Clinical and Biological Sciences, University of Torino Novara Branch aut NATIONALLICENCE 700 1- Marchisio Pier Carlo Department of Biomedical Sciences and Human Oncology, University of Torino Italy Department of Biological and Technological Research, San Raffaele Scientific Institute Milano, Italy aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/7(1996-04-03), 442-449 0027-8874 88:7<442 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford