Tissue microarray analysis of the prognostic value of E-cadherin, Ki67, p53, p27, survivin and MSH2 expression in upper urinary tract transitional cell carcinoma.
OBJECTIVE
Invasive upper urinary tract transitional cell carcinoma (UUT-TCC) has a poor prognosis (survival <50% at 5 years), and tumor stage and grade often fail to predict outcome. Our purpose was to establish whether the expression of Ki67, p53, p27, E-cadherin, survivin or MSH2 can provide prognostic information in UUT-TCC.


METHODS
The following data from the files of 62 patients treated for UUT-TCC over 12 years were collated: age at diagnosis, prior history of cancer, tobacco consumption, tumor stage (including surgical margins) and grade, and disease progression. Immunohistochemistry (IHC) for Ki67, p53, p27, E-cadherin, survivin and MSH2 was performed on tissue microarray sections from tumor tissue.


RESULTS
Overall, 31 patients died with metastasis from UUT-TCC. Mean survival was 20+/-16 months (range 2-83). In a univariate analysis, advanced age (>68 years), high stage, and loss of E-cadherin and high Ki67 expression were associated with a poor prognosis and disease recurrence. In a multivariate analysis, the independent factors of prognosis and recurrence were E-cadherin (p=0.001; p=0.004), age (p=0.022; p=0.008), and high stage (p=0.023; p=0.008).


CONCLUSIONS
E-cadherin is a useful independent prognostic factor in UUT-TCC, for use in addition to age and tumor stage. It is of particular interest to predict recurrence in patients with low grade non-invasive tumors. Ki67 expression is informative but less significant. Survivin, p53, p27 and MSH2 have no prognostic value.
Fromont
Gaëlle
G
Institut Mutualiste Montsouris, Paris, France.
Rouprêt
Morgan
M
Amira
Najla
N
Sibony
Mathilde
M
Vallancien
Guy
G
Validire
Pierre
P
Cussenot
Olivier
O
D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D046228:Microarray Analysis; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D015999:Multivariate Analysis; D051718:MutS Homolog 2 Protein / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism*; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014571:Urologic Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D015820:Cadherins; D051034:Inhibitor of Apoptosis Proteins; D019394:Ki-67 Antigen; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D018809:Proliferating Cell Nuclear Antigen; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; C413374:p27 antigen; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein