TY - JOUR
TI - MTOR/4EBP1 signaling and MMR status in colorectal cancer: New
correlations and arising perspectives
AU - Zouki, Dionysia N.
AU - Giannopoulou, Ioanna
AU - Alexandrou, Paraskevi Th
AU - and Karatrasoglou, Eleni A.
AU - Pilichos, Georgios
AU - Stamopoulos,
AU - Konstantinos
AU - Kanellis, Theodore
AU - Roupou, Eirini
AU - Saetta,
AU - Angelica A.
AU - Thymara, Irini
AU - Kavantzas, Nikolaos
AU - Lazaris,
AU - Andreas C.
JO - PATHOLOGY RESEARCH AND PRACTICE
PY - 2021
VL - 228
TODO - null
SP - null
PB - Elsevier GmbH
SN - 0344-0338
TODO - 10.1016/j.prp.2021.153655
TODO - PmTOR; P4EBP1; MMR status; Prognosis; MTOR targeted therapy
TODO - This is the first study aiming to investigate mTOR signaling and its
relation to mismatch repair status (MMR status) in colorectal cancer
(CRC). MMR status and the phosphorylated proteins, pmTOR and p4EBP1,
have been immunohistochemically analyzed in 108 formalin-fixed,
paraffin-embedded CRC specimens. The correlations between them and with
clinicopathological data, MAPK pathway (KRAS, NRAS, BRAF) as well as
their impact on patients’ overall survival have been statistically
analyzed. Our results indicated that positive pmTOR expression was
significantly associated with KRAS mutations (p = 0.004). From
multivariate survival analysis, only p4EBP1 expression emerged as
independent adverse prognostic factor for overall survival (HR, 3.322;
95%CI, 1.110-9.945; p = 0.032). Furthermore, MMR deficient carcinomas
tend to express low p4EBP1 protein levels (p = 0.002). A survival
analysis stratified by MMR status and p4EBP1 expression, showed that MMR
proficient tumours with high p4EBP1 expression had the worst overall
survival compared with the other examined subgroups (p = 0.019). In
conclusion, MAPK and PI3k/Akt pathways seem to be simultaneously
overactivated in CRC. P4EBP1 could be used as a prognostic biomarker. By
further analyzing the significant association between MMR status and
p4EBP1 expression, we suggest that MMR deficient tumours could represent
a subpopulation most likely to derive treatment benefit from mTOR
inhibition.
ER -