Abstract
e22010 Background: Tumor hipoxia induces the up-regulation of several genes via the hipoxia-inducible transcription factors (HIF) 1 and 2. HIF-2 alpha (HIF-2 α) and HIF-1 alpha (HIF-1α) are associated with the prognosis of operable NSCLC patients. We studied the immunohistochemical expression of HIF-1α and HIF-2 α in patients with NSCLC and the possible correlation with the maximum standardised uptake value (max SUV) of 18F-FDG as well as other biological parameters. Methods: We used a Tissue Arrayer device (Beecher Instruments. WI) to construct a TMA block, according to conventional protocols for the study of immunohistochemical expression of HIF-1α, HIF-2 α, EGFR, bcl-2, MIB1, p16, p63 and cyclins A, B1, D1 and D3. Sections were scored as positive if >10% of cells stained positively. Staining patterns were correlated to clinical variables. Results: HIF- 1α expression was observed in 84/96 patients (34/39 adenocarcinomas and 50/57 squamous cell carcinomas), however it did not correlate with clinical stage (I-II: 41/45 vs III-IV: 44/51). HIF-1α correlated positively with HIF-2 α (p:0,001) and EGFR (p:<0,001) expressions. The maxSUV values of 18F-FDG-PET were higher (p:0,039) in HIF-1α -positive (17,1±8,6) than in negative tumors (11,8±4,4). HIF-2 α expression was observed in 60/103 cases (27/42 adenocarcinomas and 33/61 squamous cell carcinomas) and it did not correlate with clinical stage ((I-II: 28/45 vs III-IV: 32/57). HIF-2 α correlated positively with HIF-1α (p:0,001), MIB1 (p:0,045) and EGFR (p:0,091) expressions. After multivariate analysis, only the clinical stage (RR: 2,2) was a prognostic factor. Conclusions: 1) HIF-1α and HIF-2 α expressions are frequent in patients with NSCLCs and it did not correlate with clinical stage; 2) maxSUVs FDG-PET values were higher in HIF1alpha positive than in HIF-1α negative patients; 3) HIF-1α was correlated with EGFR expression, while HIF-2 α was correlated with MIB1 expression. No significant financial relationships to disclose.
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