ARTICLE IN PRESS
G Model
Rev Esp Med Nucl Imagen Mol. 2019;xxx(xx):xxx–xxx
Original Article
Relationships between hypoxia induced factor-1 and
18
F-FDG
PET/CT parameters in colorectal cancer
Zekiye Hasbek
a,*
, Hatice Ozer
b
, Seyit Ahmet Erturk
a
, Eda Erdis ¸
c
, Birsen Yucel
c
, Esra C ¸ iftc ¸ i
d
,
Ali C ¸ akmakcilar
a
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
a r t i c l e i n f o
Article history:
Received 15 January 2019
Accepted 2 May 2019
Available online xxx
Keywords:
Hypoxia-inducible factor 1-
Colorectal cancer
18
F-FDG PET/CT
Hypoxia
a b s t r a c t
Aim: The hypoxia-inducible factor 1 (HIF-1) has a critical role in oxygen homeostasis and it is a tran-
scriptional activator of angiogenesis, erythropoiesis, iron and glucose metabolism. Glucose metabolism
rate is increased in some tumours via HIF-1. Our aim is to evaluate the relationship between hypoxia in
colorectal cancer, PET parameters, necrotic tissue size and pathologic prognostic factors via using HIF-1.
Materials/Methods: 70 patients (28F/42M; median age: 63 years) who were diagnosed with colorectal can-
cer via biopsy were staged with preoperative PET/CT and operated subsequently. Immunohistochemical
evaluation scoring was done according to nuclear HIF-1 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 = .403, p = .001 and r = .500, p = .0001, respectively). There were no statistically significant rela-
tionships between HIF-1 expression levels and tumour SUVmax, TLG, MTV, TV, %TmNcr, tumour stage,
lymphovascular invasion, perineural invasion and extracapsular/capsular LN involvement. On the other
hand, strong nuclear immunohistochemical staining was seen in tumour cells adjacent to invasive bor-
der, 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 pres-
ence of HIF-1 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-1 plays a role in the invasion area of tumour
microenvironment.
© 2019 Published by Elsevier Espa ˜ na, S.L.U. on behalf of Sociedad Espa ˜ nola de Medicina Nuclear e
Imagen Molecular.
Relaciones entre el factor-1 inducido por hipoxia y los parámetros de la
PET/TC con
18
F-FDG en el cáncer colorrectal
Palabras clave:
Factor 1- Inducido por Hipoxia
Cáncer Colorrectal
18
F-FDG PET/TC
Hipoxia
r e s u m e n
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-1. Nuestro objetivo es evaluar
la relación entre hipoxia en el cáncer colorrectal, los parámetros de PET, el tama ˜ no del tejido necrótico y
los factores pronósticos patológicos mediante el uso de HIF-1.
Materiales/Métodos: 70 pacientes (28mujeres/42hombres; promedio de edad: 63 a˜ nos) diagnosticados
con cáncer co-lorrectal mediante biopsia, se estadificaron con PET/TC preoperatoria y se operaron poste-
riormente. La puntuación de evaluación inmunohistoquímica se realizó de acuerdo con la expresión de
HIF-1 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.
Please cite this article as: Hasbek Z, Ozer H, Erturk SA, Erdis ¸ E, Yucel B, C ¸ iftc ¸ i E, et al. Relaciones entre el factor-1 inducido por hipoxia y los parámetros de la 18F-FDG
PET/TC en el cáncer colorrectal. Rev Esp Med Nucl Imagen Mol. 2019. https://doi.org/10.1016/j.remn.2019.05.006
*
Corresponding author.
E-mail address: hasbekz@yahoo.com (Z. Hasbek).
2253-8089/© 2019 Published by Elsevier Espa ˜ na, S.L.U. on behalf of Sociedad Espa ˜ nola de Medicina Nuclear e Imagen Molecular.
REMNIE-1082; No. of Pages 7