Universidad de Murcia, Departamento de Biologia Celular e Histiologia
Abstract
Introduction. The transmembrane channel
protein DOG1 (Discovered on GIST1) is normally
expressed in the gastrointestinal interstitial cells of Cajal
and also in gastrointestinal stroma tumors arising from
these cells. However, there is also evidence for a
relevant role of DOG1 expression in colorectal cancers.
This study was undertaken to search for associations
between DOG1 expression and colon cancer phenotype
and key molecular alterations.
Methods. A tissue microarray containing samples
from more than 1,800 colorectal cancer patients was
analyzed by immunohistochemistry.
Results. DOG1 immunostaining was detected in 503
(30.2%) of 1,666 analyzable colorectal cancers and
considered weak in 360 (21.6%), moderate in 78 (4.7%),
and strong in 65 (3.9%). Strong DOG1 immunostaining
was associated with advanced pT stage (p=0.0367) and
nodal metastases (p=0.0145) but these associations were
not retained in subgroups of 1,135 mismatch repair
proficient and 86 mismatch repair deficient tumors.
DOG1 positivity was significantly linked to several
molecular tumor features including mismatch repair
deficiency (p=0.0034), BRAF mutations (p<0.0001),
nuclear p53 accumulation (p=0.0157), and PD-L1
expression (p=0.0199) but unrelated to KRAS mutations
and the density of tumor infiltrating CD8 positive
lymphocytes.
Conclusion. Elevated DOG1 expression is frequent
in colorectal cancer and significantly linked to important
molecular alterations. However, DOG1 overexpression
is largely unrelated to histopathological parameters of
cancer aggressiveness and may thus not serve as a
prognostic parameter for this tumor entity