Expression of HIF-1a in advanced non small cell lung cancer, comparison between patients with bone metastasis and without bone metastasis, the influence of smoking habit: a retrospective analysis over two years of recruitment

Background: HIF-1 is a transcription factor that allows cells to adapt to hypoxia. It consists of two forms HIF-1a and HIF-1ß. It is able upon activation, in hypoxia condition, to foster several oncogenes and proteins which in turn are involved in carcinogenesis, cell invasion and migration. Aim: to verify if HIF-1a tissue expression is associated with lung cancer bone metastasis process and evaluate its influence on prognosis. Methods: a retrospective analysis was carried out on samples deriving from bronchial biopsy and CT-guided trans-thoracic needle biopsy. The data collected concerned advanced NSCLC patients and included age, staging, detailed histotype, pack-year, comorbidities. Detection of HIF-1 expression was performed by the use of a murine specific antibody. A comparison was carried out between group with visceral metastases and group having also bone metastases. Results: a total of 146 patients with mean age of about 70 were considered, the prevalent histotype was adenocarcinoma(67.1%). Former smokers accounted for 58.9%. The mean pack-year was 36.4. CT-guided trans-thoracic biopsy was the main source of the specimens. The population was subdivided in two groups based on the presence or absence of bone metastasis and the comparison showed non-significant differences about ECOG PS, age, cardiovascular comorbidities. Significant differences were detected about pack-year(p = 0.02), time to progression(TTP)(p = 0.001) and COPD comorbidity(p = 0.04). The Kaplan-Meier method with Log-rank test applied on survival analysis comparing the subgroups showed a longer TTP in patients with visceral metastases with HR of 1.3 and p = 0.14. The sample available for immunohistochemistry detection of HIF-1 a consisted of 61 patients. A higher intensity of expression along with higher positive cells percentage was recorded in the group with bone metastases. The main variable affecting HIF expression was the presence of bone metastasis(p = 0.01), whereas histotype seems to influence the TTP(p = 0.04).The product of intensity for percentage of positive cells was significantly higher in the group with bone metastases (p = 0.02). Conclusions: patients affected by NSCLC IV stage with both visceral and bone metastases have lower survival than those with only visceral metastases. The presence of bone metastasis is tightly linked with the expression of HIF-1a. The intensity combined with the percentage of positive expression is higher in patients with bone metastasis than in patients without it, suggesting a role of HIF-1a in cancer progression.