Strong immunohistochemical expression of fibroblast growth factor receptor 3, superficial staining pattern of cytokeratin 20, and low proliferative activity define those papillary urothelial neoplasms of low malignant potential that do not recur.
BACKGROUND
Papillary urothelial neoplasm of low malignant potential (PUNLMP) is a clinically significant lesion because recurrence occurs in approximately 35% of patients. To date, it is not possible to identify those cases that will recur based on conventional histopathologic assessment. The objective of the current study was to evaluate immunohistochemically tissue expression of fibroblast growth factor receptor 3 (FGFR3), cytokeratin 20 (CK20), and MIB-1 in nonrecurrent and recurrent PUNLMP.


METHODS
FGFR3, CK20, and MIB-1 were investigated by immunohistochemistry (IHC) in 80 PUNLMP cases (41 nonrecurrent and 39 recurrent), in 4 cases of normal urothelium (NU), and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). Statistics included discriminant analysis.


RESULTS
NU demonstrated a weak to moderate FRFG3 staining intensity, a superficial pattern of CK20 staining, and low proliferative activity. UC was found to have FGFR3 staining similar to NU, an abnormal CK20 expression, and high proliferative activity. The nonrecurrent PUNLMP group demonstrated strong FGFR3 intensity in 80.5% of the cases (vs 56.4% of the recurrent cases), a superficial CK20 staining pattern in 53.7% of the cases (vs 28.2% of the recurrent cases), and a percentage of MIB-1-positive nuclei below the median value of all the PUNLMP cases in 61% of the cases (35.9% in the recurrent cases). The differences were statistically significant. Discriminant analysis based on these 3 features demonstrated that 67.5% of cross-validated grouped PUNLMP cases were correctly allocated, with 73.2% of the nonrecurrent and 61.5% of the nonrecurrent cases being correctly classified. The specificity and sensitivity were 73.1% and 61.5%, respectively.


CONCLUSIONS
Strong immunohistochemical expression of FGFR3, a superficial staining pattern of CK20, and a low proliferative activity define those papillary urothelial neoplasms of low malignant potential that do not recur.
Barbisan
Francesca
F
Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Ancona, Italy.
Santinelli
Alfredo
A
Mazzucchelli
Roberta
R
Lopez-Beltran
Antonio
A
Cheng
Liang
L
Scarpelli
Marina
M
van der Kwast
Theodorus
T
Montironi
Rodolfo
R
D014408:Biomarkers, Tumor / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053554:Keratin-20 / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism; D011237:Predictive Value of Tests; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology*; D019459:Urothelium / Q000378:metabolism / Q000473:pathology
D014408:Biomarkers, Tumor; D053554:Keratin-20; D019394:Ki-67 Antigen; C496365:FGFR3 protein, human; D051498:Receptor, Fibroblast Growth Factor, Type 3