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MicroRNA expression profile in tissue from complete transurethral resection for clinical stage T1 bladder cancer predicts pathologic upstaging
John E. Humphrey, MD, Kai H. Hammerich, MD, Sheaumei Tsai, MD, John A. Libertino, MD, Jason R. Gee, MD, Antonia H. Holway, PhD, Kimberly Rieger-Christ, PhD.
Lahey Clinic, Burlington, MA, USA.

BACKGROUND:
Greater than 40% of patients with clinical stage T1 carcinoma at transurethral resection of the bladder tumor (TURBT) are upstaged to muscle invasive disease at cystectomy. In this study, we investigated the potential of a panel of microRNAs previously correlated with invasion to predict which T1 biopsies are likely to be upstaged. If upstaging could be predicted it may help to identify cases where early cystectomy is warranted.
METHODS:
All patients underwent TURBT and were diagnosed with T1 disease prior to cystectomy. No patients received neoadjuvant chemotherapy or radiation. Patients were categorized as either accurately staged (T1) or upstaged (≥T2) at cystectomy. Sections from tissue samples were cut and stained for hematoxylin and eosin for the assessment of tumor content. Total RNA was extracted from paraffin embedded tissue from TURBT specimens and qRT-PCR of microRNAs was conducted.
RESULTS:
A total of 28 specimens were analyzed, 13 of which (46%) represented patients upstaged at cystectomy. Expression levels of five out of sixteen microRNAs previously associated with an invasive phenotype correlated significantly with pathologic upstaging. These 5 microRNAs were up-regulated in the upstaged group. Time to recurrence and cancer specific survival were shorter in the upstaged group, while microRNA levels were associated with cancer specific survival.
CONCLUSIONS:
There are differences among microRNA expression in T1 TURBT specimens that correlate with upstaging at cystectomy. With more elucidation, these differences may serve as further prognostic indicators as to which patients with T1 disease might benefit from early cystectomy.


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