Expression of phospho-mTOR kinase is abundant in colorectal cancer and associated with left-sided tumor localization.
OBJECTIVE
To investigate the significance of mammalian target of rapamycin (mTOR) in colorectal cancers. mTOR has recently been suggested as a prognostic biomarker and therapeutic target in an array of human cancers.


RESULTS
phospho-mTOR (p-mTOR) expression was analyzed by immunohistochemistry (IHC) on a tissue microarray containing 1800 colorectal cancers (CRC). Clinical follow-up data were available from all cancer patients. Positive p-mTOR immunostaining was seen in 83.5% of 1640 interpretable CRC and was considered weak in 862 (52.5%) and strong in 508 cases (31.0%). Matching clinico-pathological parameters were available in 1580 cases. p-mTOR staining was more frequent in tubular adenocarcinomas than in the less common histological subtypes (mucinous, medullary, signet cell; P=0.0163) and significantly linked to carcinomas of the left-sided colon and rectum as compared to right-sided CRC (P=0.0066). There was no significant association between p-mTOR expression and patients' gender, tumor stage, tumor grade or nodal status. In a survival analysis, p-mTOR IHC status of all CRC was unrelated to patient survival (P=0.702). In a multivariate analysis including pT, pN, tumor grade, tumor localization and p-mTOR expression, only pT, pN (both P<0.0001) and grade (P=0.0001) showed prognostic impact, but not tumor localization (P=0.9472) or p-mTOR expression (P=0.8879).


CONCLUSIONS
Our observations indicate that p-mTOR overexpression is abundant in CRC and linked to left-sided tumor localization. The high frequency and overexpression of p-mTOR is providing further rationale for targeting this pathway therapeutically in CRC patients. However, a prognostic role of p-mTOR overexpression in CRC could not be confirmed.
Department of Surgery, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Nathaniel
N
Melling
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Ronald
R
Simon
Department of Surgery, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Jakob R
JR
Izbicki
Institute of Pathology, University Hospital Basel Basel 4031, Switzerland.
Luigi M
LM
Terracciano
Department of Oncology and Hematology, Hubertus Wald Cancer Center, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Carsten
C
Bokemeyer
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Guido
G
Sauter
Institute of Pathology, University Medical Center Hamburg-Eppendorf Hamburg 20246, Germany.
Andreas H
AH
Marx
D000230:Adenocarcinoma / Q000201:enzymology* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000201:enzymology; D014408:Biomarkers, Tumor / Q000032:analysis*; D018279:Carcinoma, Signet Ring Cell / Q000201:enzymology; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D010766:Phosphorylation; D016016:Proportional Hazards Models; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases / Q000032:analysis*; D013997:Time Factors; D046888:Tissue Array Analysis; D016896:Treatment Outcome; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
Colorectal cancer; immunohistochemistry; phospho-mTOR; tissue microarray