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Inicio Revista Española de Medicina Nuclear e Imagen Molecular (English Edition) Relationships between hypoxia induced factor-1α and 18F-FDG PET/CT parameters i...
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Vol. 38. Issue 6.
Pages 355-361 (November - December 2019)
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Vol. 38. Issue 6.
Pages 355-361 (November - December 2019)
Original Article
DOI: 10.1016/j.remnie.2019.05.008
Relationships between hypoxia induced factor-1α and 18F-FDG PET/CT parameters in colorectal cancer
Relaciones entre el factor-1α inducido por hipoxia y los parámetros de la PET/TC con 18F-FDG en el cáncer colorrectal
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Zekiye Hasbeka,
Corresponding author
hasbekz@yahoo.com

Corresponding author.
, Hatice Ozerb, Seyit Ahmet Erturka, Eda Erdişc, Birsen Yucelc, Esra Çiftçid, Ali Çakmakcilara
a Cumhuriyet University, School of Medicine, Department of Nuclear Medicine, Sivas, Turkey
b Cumhuriyet University, School of Medicine, Department of Pathology, Sivas, Turkey
c Cumhuriyet University, School of Medicine, Department of Radiation Oncology, Sivas, Turkey
d Sakarya University, School of Medicine, Research and Training Hospital, Department of Nuclear Medicine, Sakarya, Turkey
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Tables (4)
Table 1. Patients and tumour characteristics.
Table 2. Correlations between 18F-FDG PET/CT parameters and percentage of tumour necrosis.
Table 3. Correlations between 18F-FDG PET/CT parameters and HIF-1α expression levels.
Table 4. The relationship between tumour stage and HIF-1α score.
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Abstract
Aim

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.

Materials/Methods

70 patients (28female/42male; 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.

Results

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.

Conclusion

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.

Keywords:
Hypoxia-inducible factor 1-α
Colorectal cancer
18F-FDG PET/CT
Hypoxia
Resumen
Objetivo

El factor inducible para hipoxia (HIF-1) tiene un papel crítico en la homeostasis del oxígeno y es un activador transcripcional de angiogénesis, eritropoyesis, hierro y metabolismo de glucosa. La tasa de metabolismo de glucosa aumenta en algunos tumores a través de HIF-1α. Nuestro objetivo es evaluar la relación entre hipoxia en el cáncer colorrectal, los parámetros de PET, el tamaño del tejido necrótico y los factores pronósticos patológicos mediante el uso de HIF-1α.

Materiales/Métodos

70 pacientes (28mujeres/42hombres; promedio de edad: 63 años) diagnosticados con cáncer co-lorrectal mediante biopsia, se estadificaron con PET/TC preoperatoria y se operaron posteriormente. La puntuación de evaluación inmunohistoquímica se realizó de acuerdo con la expresión de HIF-1α nuclear, la intensidad y la densidad de tinción. El volumen metabólico tumoral (MTV), la glucólisis de lesión total (TLG) y el volumen tumoral (TV) se calculó utilizando el volumen de una fórmula elipsoide mediante las imágenes de TC y el porcentaje de necrosis tumoral (%TmNcr) se calculó por diferencia entre TV y MTV.

Resultados

Hubo una correlación positiva moderadamente significativa entre el SUVmax del tumor y TV y el %TmNcr (r=0,403,p=0,001 y r=0,5, p=0,0001,respectivamente). No hubo una relación estadísticamente significativa entre niveles de expresión de HIF-1α y SUVmax tumoral, TLG, MTV, TV,% Tm Ncr, estadio tumoral, invasión linfovascular, invasión perineural y afectación ganglionar extracapsular/capsular. Por otro lado, se observó una fuerte tinción inmunohistoquímica nuclear en las células tumorales adyacentes al borde invasivo, las células inflamatorias. Aunque no fue estadísticamente significativa, se observó una tinción nuclear moderada o fuerte en 64,9% de los pacientes metastásicos.

Conclusión

Aunque la presencia de una correlación positiva entre SUVmax tumoral y el % de TmNcr muestra que hay células hipóxicas en tejido canceroso con una alta captación de FDG, no se demostró ninguna relación entre la presencia de HIF-1α y el incremento metabólico de glucosa y los factores patológicos del tumor. La fuerte tinción inmunohistoquímica nuclear en células tumorales adyacentes a las células inflamatorias y de borde invasivas nos hace pensar que HIF-1α desempeña un papel en el área de invasión del microambiente tumoral.

Palabras clave:
Factor 1-α Inducido por Hipoxia
Cáncer Colorrectal
18F-FDG PET/TC
Hipoxia

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