Τίτλος:
Expression of hypoxia-related tissue factors in astrocytic gliomas. A
multivariate survival study with emphasis upon carbonic anhydrase IX
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Carbonic anhydrase IX (CAIX) is a transmembrane enzyme involved in the
reversible metabolism of carbon dioxide to carbonic acid and, hence, in
physiological pH regulation. It also participates in cellular
differentiation and proliferation, its expression being absent in most
normal tissues. It has been recently postulated that the
hypoxia-inducible factor (HIF-1) pathway up-regulated by hypoxia
accounts for CAIX overexpression in most human tumors. In the present
study, we examined the expression of this enzyme in diffuse gliomas of
astrocytic origin in relation to vascular endothelial growth factor
(VEGF) and HIF-1 alpha expression, proliferation rate (as assessed with
Ki-67 antigen), microvessel morphology, and survival. Of 84 cases
analyzed, 61 cases (72.6%) displayed strong membrane and/or cytoplasmic
expression of CAIX and were grouped as positive. Immunoreactivity tended
to have a perinecrotic distribution and increased in parallel with the
extent of necrosis (P <.001) and histologic grade (P <.001). A positive
correlation was also noted with HIF-1) and VEGF expression (P <.001),
proliferation rate (P =.010), microvessel density (P =.004), and
microvessel caliber parameters (P =.014-.038). In univariate survival
analysis, increased CAIX expression was associated with shortened
survival in the entire cohort (P <.0001), along with VEGF (P =.0205) and
HIF-1 alpha levels (P=.0190). Multivariate analysis selected the
interaction model of CAIX, with grade and age as the only parameters
independently affecting survival. CAIX expression was also the only
significant parameter for the survival of patients with grades II/III.
We conclude that CAIX may be used as a prognostic indicator in diffuse
astrocytomas to refine the information provided by grade. Given the role
of CAIX in the acidification of tumor environment and its up-regulation
by hypoxia, it is thought that CAIX expression may be linked to
resistance of tumor cells to radiotherapy by allowing them to
acclimatize to a hypoxic and acidic microenvironment. (c) 2007 Elsevier
Inc. All rights reserved.
Συγγραφείς:
Korkolopoulou, Penelope
Perdiki, Marina
Thymara, Irini and
Boviatsis, Efstathios
Agrogiannis, George
Kotsiakis, Xenophon
and Angelidakis, Dimitrios
Rologis, Dimitrios
Diamantopoulou,
Kalliopi
Thomas-Tsagli, Euphemia
Kaklamanis, Loukas
Gatter,
Kevin
Patsouris, Efstratios
Περιοδικό:
HUMAN PATHOLOGY
Εκδότης:
W B SAUNDERS CO-ELSEVIER INC
Λέξεις-κλειδιά:
astrocytoma; hypoxia; HIF-1 alpha; VEGF; CAIX
DOI:
10.1016/j.humpath.2006.07.020
