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Titolo:
Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenicpathways and independently to poor outcome in non-small cell lung cancer
Autore:
Giatromanolaki, A; Koukourakis, MI; Sivridis, E; Pastorek, J; Wykoff, CC; Gatter, KC; Harris, AL;
Indirizzi:
Democritus Univ Thrace, Tumour & Angiogenesis Res Grp, Dept Radiotherapy Oncol, Alexandroupolis 68100, Greece Democritus Univ Thrace Alexandroupolis Greece 68100 upolis 68100, Greece Democritus Univ Thrace, Tumour & Angiogenesis Res Grp, Dept Pathol, Alexandroupolis 68100, Greece Democritus Univ Thrace Alexandroupolis Greece 68100 upolis 68100, Greece Slovak Acad Sci, Inst Virol, Bratislava, Slovakia Slovak Acad Sci Bratislava Slovakia i, Inst Virol, Bratislava, Slovakia Oxford Radcliffe Hosp, Dept Cellular Sci, Oxford OX3 9DS, England Oxford Radcliffe Hosp Oxford England OX3 9DS ci, Oxford OX3 9DS, England Oxford Radcliffe Hosp, Inst Mol Med, Oxford OX3 9DS, England Oxford Radcliffe Hosp Oxford England OX3 9DS ed, Oxford OX3 9DS, England
Titolo Testata:
CANCER RESEARCH
fascicolo: 21, volume: 61, anno: 2001,
pagine: 7992 - 7998
SICI:
0008-5472(20011101)61:21<7992:EOHCAR>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
THYMIDINE PHOSPHORYLASE; EPISIALIN MUC1; NORMAL-TISSUES; GROWTH-FACTOR; MN/CA9 GENE; MN ANTIGEN; TUMORS; CARCINOMA; BIOMARKER; INHIBITOR;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
44
Recensione:
Indirizzi per estratti:
Indirizzo: Giatromanolaki, A Tumour & Angiogenesis Res Grp, 18 Dimokratias Ave, Iraklion 71306, Crete, Greece Tumour & Angiogenesis Res Grp 18 Dimokratias Ave Iraklion Crete Greece 71306
Citazione:
A. Giatromanolaki et al., "Expression of hypoxia-inducible carbonic anhydrase-9 relates to angiogenicpathways and independently to poor outcome in non-small cell lung cancer", CANCER RES, 61(21), 2001, pp. 7992-7998

Abstract

Carbonic anhydrase-9 (CA9), a transmembrane enzyme with an extracellular active site, is involved in the reversible metabolism of the carbon dioxide to carbonic acid. Up-regulation of CA by hypoxia and the hypoxia-inducible factor (HIF) pathway has been recently postulated (Wykoff et al. Cancer Res., 60: 7075-7083, 2000). In the present study we examined the expression ofthis enzyme in non-small cell lung cancer. Of 107 cases analyzed, 39 (36.4%) had strong membrane/cytoplasmic expression of CA9 and were grouped as positive. The staining was confined around areas of necrosis, and a significant association of CA9 expression with the extent of necrosis was noted (P =0.004). Nevertheless, 38 of 74 cases with focal or extensive necrosis did not express CA9. CA9 expression was more frequent in the squamous cell histology (P = 0.001) and with advanced T stage (P = 0.009). A significant coexpression of CA9 with platelet-derived endothelial cell growth factor and basic fibroblast growth factor receptor expression was noted. Double stainingof CA9 with anti-CD31 monoclonal antibody revealed an overall higher microvessel density in the areas expressing CA9 than in negative areas (P = 0.0005). Thirty-one of 38 CA9-positive cases were positive for HIF1a/HIF2a, butHIF positivity was a more common event (68 of 107) and their patterns of expression were diffuse (not confined in the necrotic areas). A direct association of CA9 expression with epidermal growth factor receptor, c-erbB-2, and MUC1 expression was also noted (P < 0.04). Survival analysis showed thatCA9 expression is related to poor prognosis. CA9 expression in tumors withlow vascularization defined a prognosis similar to the one of patients with highly angiogenic tumors. Multivariate analysis revealed that CA9 expression is a significant prognostic factor independent of angiogenesis. We conclude that CA9 is an important molecule in non-small cell lung cancer, the up-regulation of which occurs in highly hypoxic/necrotic regions of the tumors. The expression of CA9 is linked to the expression of a constellation ofproteins involved in angiogenesis, apoptosis inhibition, and cell-cell adhesion disruption, which explains the strong association of CA9 with poor outcome.

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Documento generato il 05/07/20 alle ore 21:40:31