6533b834fe1ef96bd129e132
RESEARCH PRODUCT
Intracellular signalling via the AKT axis and downstream effectors is active and prognostically significant in cancer of unknown primary (CUP): a study of 100 CUP cases.
Vassilis GolfinopoulosGeorge PentheroudakisAnna GoussiaV. SiozopoulouM. BobosD. KrikelisA. CervantesT. CiuleanuM. MarselosGeorge FountzilasVassiliki D. Malamou-mitsiNicholas PavlidisVassilis GolfinopoulosGeorge PentheroudakisAnna GoussiaV. SiozopoulouM. BobosD. KrikelisA. CervantesT. CiuleanuM. MarselosGeorge FountzilasVassiliki D. Malamou-mitsiNicholas Pavlidissubject
OncologyMalePathologyP21Signal transductionMitogen activated protein kinaseTissue microarrayCancer riskNeoplasmsSquamous cell carcinomaCarcinomatous peritonitisCancer of unknown primary (cup)MedicineOverall survivalPriority journalSurvival timeUnivariate analysisTissue microarraybiologyUnknown primaryHematologyClassificationPrognosisImmunohistochemistryPtenRetrospective studyOncologyIntracellular signalingImmunohistochemistryFemaleCyclin d1Cancer tissueProtein p21HumanSignal Transductionmedicine.medical_specialtyTranslational studyMajor clinical studyCancer mortalityAdenocarcinomaArticleCyclin D1Disease associationInternal medicineTissue array analysisPTENHumansHuman tissueProtein kinase BPI3K/AKT/mTOR pathwayCancer prognosisSurvival predictionDigestive system cancerbusiness.industryAkt/PKB signaling pathwayAktCancer of unknown primary siteProto-oncogene proteins c-aktRps6Protein kinase bTissue Array Analysisbiology.proteinProtein expressionProgression free survivalProtein s6Neoplasms Unknown PrimarybusinessTissue preparationProto-Oncogene Proteins c-aktdescription
Background: Hypothesising that cancer of unknown primary (CUP) may harbour unique characteristics, we present a translational study of the immunohistochemical expression and clinical correlation of key PTEN/AKT pathway molecules. Patients and methods: We collected 100 paraffin-embedded CUP tissue blocks. We studied using tissue microarrays the expression of PTEN, phospho-AKT, Cyclin D1, p21, phospho-RPS6. From the percentage of staining tumour cells and the literature, we selected cut-offs to classify the expression of each biomolecule. We correlated IHC expression with clinical data. Results: PTEN, pAKT, and pRPS6 showed frequent expression. At univariate analysis, high IHC expression of pAKT and pRPS6 displayed statistically significant association with worse survival. Prognosis was worse upon concurrent high IHC expression of pMAPK and pAKT median overall survival = 8 months [95% confidence interval (CI) 5.3-10.7] versus 17 months [95% CI 13.1-20.9]. In multivariate analysis, high p21 was associated with better survival (risk ratio [RR] = 0.34 [95% CI 0.16-0.73], P = 0.005). High expression of pAKT (RR = 2.39 [95% CI 1.23-4.66], P = 0.01) or pRPS6 (RR = 2.76 [95% CI 1.31-5.84], P = 0.008) was associated with worse survival. Conclusions: p21 expression conferred favourable prognosis, while high pAKT or pRPS6 expression predicted worse prognosis. Concurrent MAPK and pAKT expression had a marked adverse impact on survival. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. 23 10 2725 2730
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2012-10-01 | Annals of oncology : official journal of the European Society for Medical Oncology |