Overexpression of the mammalian target of rapamycin: a novel biomarker for poor survival in resected early stage non-small cell lung cancer.
BACKGROUND
The best hope of cure for patients with non-small cell lung cancer (NSCLC) is surgical resection. However, even in stage IA patients, 30% die within 5 years. Further improvements in survival require a biomarker(s), which defines the subset of these patients destined to do badly so that they could be targeted for additional therapies. Here, we investigate whether the immunohistochemical expression of a key kinase implicated in lung cancer biology, the mammalian target of rapamycin (mTOR) can predict survival outcome in patients with early stage resected NSCLC.


METHODS
One hundred thirty-four patients with resected early stage (IA-IIB) NSCLC were pathologically reviewed centrally before staining for mTOR. Multiple variables including age, sex, stage, angioinvasion, lymph node status, and mTOR staining were assessed by univariate and multivariate analyses.


RESULTS
Stage (p = 0.044), lymph node status (p = 0.049), angioinvasion (p = 0.017), and mTOR staining (p = 0.007) were significant univariate predictors of poor survival. However, only angioinvasion (p = 0.016) and mTOR staining (p = 0.046) remained significant after multivariate analysis. Moreover, mTOR staining was the only variable to predict poor outcome in patients who either had negative lymph nodes (p = 0.016) or were stage IA (p = 0.0016).


CONCLUSIONS
The mTOR staining provides a new biomarker for poor outcome in early stage NSCLC and could enable resected stage IA patients to be selected for novel therapies possibly with an mTOR inhibitor.
Dhillon
Tony
T
CR-UK Laboratories, Imperial College London, Hammersmith Hospitals campus, London, United Kingdom.
Mauri
Francesco A
FA
Bellezza
Guido
G
Cagini
Lucio
L
Barbareschi
Mattia
M
North
Bernard V
BV
Seckl
Michael J
MJ
D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008175:Lung Neoplasms / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015996:Survival Rate; D058570:TOR Serine-Threonine Kinases; D046888:Tissue Array Analysis
D047908:Intracellular Signaling Peptides and Proteins; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases