title: Expression and clinical implication of cyclooxygenase-2 and E-cadherin in oral squamous cell carcinomas.
abstract: Epithelial-Mesenchymal Transition (EMT) and angiogenesis are crucial events for development of aggressive and often fatal Oral Squamous Cell Carcinomas (OSCCs). Bothpromote cancer progression and metastasis development, but while the former induces the loss of E-cadherin expression and, hence cadherin switching; the latter produces hematicblood vessel neo-formation and contribute to OSCC cell growth, tumor mass development, and dissemination.Cyclooxygenase-2 (COX-2)has an important role, not only in angiogenic mechanisms, but also in favoring cancer invasion. Indeed it decreases the expression of E-cadherin and leads to phenotypic changes in epithelial cells (EMT) enhancing their carcinogenic potential. Our aim is to evaluate the interplay between E-cadherin cytoplasmic delocalization, COX-2 up-regulation and COX-2 induced neo-angiogenesis in 120 cases of OSCC. We have analyzed the distribution and the number of neo-formed endothelial buds surrounding infiltrating cells that express COX-2, as well as the neo-formed vessels in chronic inflammatory infiltrate, which surround the tumor. A double immunostaining method was employed in order to verify co-localization of endothelial cell marker (CD34) and COX-2. IHC has also been used to assess E-cadherin expression. Our data demonstrate that the OSCC cells, which lose membranous E-cadherin staining, acquiring a cytoplasmic delocalization, overexpress COX-2. Moreover, we find a new CD34+ vessel formation (sprouting angiogenesis). Only basaloid type of OSCC showes low level of COX-2 expression together with very low level of neo-angiogenesis and consequent tumor necrosis. The well-known anti-metastatic effect of certain COX-2 inhibitors suggests that these molecules might have clinical utility in the management of advanced cancers.
authors.affiliation: Department of Anatomic Pathology, 'Giovanni Paolo II' Foundation-UCSC , Campobasso, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Santoro
authors.affiliation: Department of Clinical and Experimental Medicine, Institute of Pathological Anatomy, University of Foggia , Foggia, Italy.
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Bufo
authors.affiliation: Department of Clinical and Experimental Medicine, Institute of Pathological Anatomy, University of Foggia , Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Russo
authors.affiliation: Department of Clinical and Experimental Medicine, Institute of Pathological Anatomy, University of Foggia , Foggia, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Cagiano
authors.affiliation: Laboratory of Head and Neck Cancer Invasion and Metastasis, Department of Otolaryngology, Head and Neck Oncology, University of Michigan, Medical School , Ann Arbor, MI, USA.
authors.forename: Silvana
authors.initials: S
authors.lastname: Papagerakis
authors.affiliation: Department of Neuroscience, Reproductive and Odontostomatologies Science, University of Naples 'Federico II' , Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bucci
authors.affiliation: Section of Pathological Anatomy, National Cancer Institute 'G. Pascale Foundation' , Naples, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Aquino
authors.affiliation: Head and Neck Medical Oncology Unit, National Cancer Institute 'G. Pascale Foundation' , Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Longo
authors.affiliation: Department of Biology, University of Naples , Naples, Italy.|Department of Biochemistry, Biophisic and General Pathology Second University of Naples , Naples, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Feola
authors.affiliation: Department of Medicine, Surgery and Neuroscience, University of Siena , Siena, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University , Philadelphia, PA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Giordano
authors.affiliation: Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome , Rome, Italy.
authors.forename: Angelina
authors.initials: A
authors.lastname: Di Carlo
authors.affiliation: Department of Biochemistry, Biophisic and General Pathology Second University of Naples , Naples, Italy.|Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University , Philadelphia, PA, USA.
authors.forename: Marina
authors.initials: M
authors.lastname: Di Domenico
authors.affiliation: Department of Clinical and Experimental Medicine, Institute of Pathological Anatomy, University of Foggia , Foggia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pannone
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000473:pathology; D059016:Tumor Microenvironment
chemical_list: D015820:Cadherins; D051546:Cyclooxygenase 2
keywords:  Prostaglandins ; CD-34; Cox-2; E-cadherin; OSCC; TMA; neo-angiogenesis; tumor microenvironment