Grade progression and regression in recurrent urothelial cancer.
OBJECTIVE
Recurrent urothelial cancers are reported to have characteristics similar to those of the primary tumor, with 10% to 25% of low grade tumors recurring as high grade disease. We determined how often grade progression and regression occur and whether abnormalities in p53 protein expression in original tumors are preserved in recurrences.


METHODS
Two groups of patients treated for recurrent stages Ta/T1 urothelial bladder cancers with at least 1 tumor-free examination between the index and recurrent tumors were reviewed. Group 1 included 115 patients in whom the first available tumor was compared with the last recurrence and group 2 included 42 in whom the initial tumor was compared with the first recurrence. Immunohistochemical analysis of p53 expression was performed on a subset of 34 tumor pairs.


RESULTS
In group 1, 33 grade 3 tumors (45%) recurred as grade 1 or 2 tumors, while 9 of 82 grades 1 and 2 tumors (11%) recurred as grade 3 tumors. Five of 7 group 2 grade 3 tumors (71%) recurred as grade 1 or 2 disease, while 1 of 35 grades 1 and 2 tumors (3%) recurred as grade 3 disease. In the 34 pairs studied immunohistochemically 6 of 14 grade 3 tumors recurred at lower grades. Nuclear p53 over expression occurred in 21 index tumors (12 of 14 grade 3, 8 of 17 grade 2 and 1 of 3 grade 1) and in 9 recurrences (6 of 10 grade 3, 2 of 17 grade 2 and 1 of 7 grade 1). Only 7 of 21 p53 positive and 2 of 12 p53 negative index tumors were p53 positive on recurrence.


CONCLUSIONS
While progression from low to high grade occurred in less than 15% of patients, grade regression was observed in almost 50%. The loss of p53 positivity in regressing tumors indicates that these recurrences are molecularly distinct from the corresponding initial tumor.
Borhan
Ali
A
Department of Urology, University of Rochester, Rochester, New York 14642, USA.
Reeder
Jay E
JE
O'Connell
Mary J
MJ
Wright
Kate O
KO
Wheeless
Leon L
LL
di Sant'Agnese
P Anthony
PA
McNally
Melanie L
ML
Messing
Edward M
EM
D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008137:Longitudinal Studies; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000737:chemistry / Q000473:pathology* / Q000628:therapy; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000473:pathology* / Q000628:therapy
D016159:Tumor Suppressor Protein p53