Relationships between hypoxia induced factor-1α and ¹⁸F-FDG PET/CT parameters in colorectal cancer

The hypoxia-inducible factor 1 (HIF-1) has a critical role in oxygen homeostasis and it is a transcriptional activator of angiogenesis, erythropoiesis, iron and glucose metabolism. Glucose metabolism rate is increased in some tumours via HIF-1α. Our aim is to evaluate the relationship between hypoxia in colorectal cancer, PET parameters, necrotic tissue size and pathologic prognostic factors via using HIF-1α.

70 patients (28 female/42 male; median age: 63 years) who were diagnosed with colorectal cancer via biopsy were staged with preoperative PET/CT and operated subsequently. Immunohistochemical evaluation scoring was done according to nuclear HIF-1α expression, staining density and intensity. Metabolic tumour volume (MTV), total lesion glycolysis (TLG) and tumour volume (TV) were calculated by using volume of an ellipsoid formula via CT images, and percentage of tumour necrosis (%TmNcr) that was calculated by the difference between TV and recorded MTV.

There was a moderately meaningful positive correlation between tumour SUVmax and TV and %TmNcr (r=0.403, p=0.001 and r=0.500, p=0.0001, respectively). There were no statistically significant relationships between HIF-1α expression levels and tumour SUVmax, TLG, MTV, TV, %TmNcr, tumour stage, lymphovascular invasion, perineural invasion and extracapsular/capsular lymph node involvement. On the other hand, strong nuclear immunohistochemical staining was seen in tumour cells adjacent to invasive border, inflammatory cells. Although not statistically significant, moderate or strong nuclear staining were seen in 64.9% of metastatic patients.

Although the presence of a positive correlation between tumour SUVmax and %TmNcr shows that there are hypoxic cells in cancer tissue with high FDG uptake, the relationship between the presence of HIF-1α and enhanced glucose metabolism and pathological prognostic factors of tumour was not shown. Strong nuclear immunohistochemical staining in tumour cells adjacent to invasive border and inflammatory cells leads us to believe that HIF-1α plays a role in the invasion area of tumour microenvironment.