Predicting outcome in minimally invasive (T1a and T1b) urothelial bladder carcinoma using a panel of biomarkers: a high throughput tissue microarray analysis.
OBJECTIVE
To evaluate the protein expression of fibroblast growth factor receptor-3 (FGFR3), hamartin, 14-3-3sigma, Aurora-A, and E-cadherin using immunohistochemistry (IHC) in a series of human bladder carcinomas and to evaluate their value in distinguishing T1a from T1b tumours and in predicting their behaviour, as T1 urothelial bladder tumours present great diagnostic and therapeutic challenges to pathologists and clinicians.


METHODS
Tissue microarrays were constructed from 94 patients (Ta 20, T1a 31, T1b 14, and T2 29 patients) using tissue obtained at first disease presentation.


RESULTS
FGFR3 and 14-3-3sigma were the only markers that were significantly associated with tumour grade and 14-3-3sigma was significantly associated with tumour stage. Furthermore, none of these markers could help in distinguishing T1a from T1b tumours. After adjusting for the E-cadherin expression, FGFR3 expression was a significant factor in predicting the time to recurrence in T1a/T1b. Furthermore, among all the clinical variables, grade and depth of invasion were the only ones that had a significant value in predicting T1a/T1b tumour progression.


CONCLUSIONS
Even though the staging of T1 to T1a/T1b is not a common practice and it is not included in the Tumour-Node-Metastasis classification, our data clearly confirmed the importance of a proper sub-staging of T1 tumours whenever feasible.
Mhawech-Fauceglia
Paulette
P
Department of Pathology and Laboratory Medicine at Roswell Park Cancer Institute, Buffalo, NY, USA. pmhawech1@yahoo.com
Fischer
Gabor
G
Alvarez
Victor
V
Ahmed
Arsalan
A
Herrmann
François R
FR
D048948:14-3-3 Proteins / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D064127:Aurora Kinases; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging / Q000379:methods; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism; D046888:Tissue Array Analysis / Q000379:methods; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D048948:14-3-3 Proteins; D014408:Biomarkers, Tumor; D015820:Cadherins; C000624650:TSC1 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D051498:Receptor, Fibroblast Growth Factor, Type 3; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases