Telomere Shortening Distinguishes Inverted Papilloma of the Urinary Bladder from Urothelial Carcinoma with Inverted Growth
Sean R Williamson, Shaobo Zhang, Antonio Lopez-Beltran, Rodolfo Montironi, Liang Cheng. Indiana University School of Medicine, Indianapolis; Cordoba University, Cordoba, Spain; Polytechnic University of the Marche Region (Ancona), Ancona, Italy
Background: Inverted papilloma of the urinary bladder is considered to be a benign neoplasm, characterized by thin inter-anastomosing cords of invaginating urothelial cells, often similar in morphologic appearance to florid von Brunn's nests or cystitis cystica/glandularis of the usual type. However, urothelial carcinoma may occasionally demonstrate a similar inverted growth pattern, creating a challenging differential diagnosis and raising the question of whether the two entities are related. As telomere shortening has been implicated in the development of epithelial malignancy, we investigated relative telomere length in inverted papilloma and urothelial carcinoma with an inverted growth pattern.
Design: Formalin-fixed, paraffin-embedded tissue sections from 59 cases were studied, including 26 cases of inverted papilloma, 9 cases of urothelial carcinoma with inverted growth, and 12 cases of cystitis glandularis. Normal urothelium from the same slide for each of the designated lesions was used as a normal control. Quantitative fluorescence in situ hybridization (FISH) was performed on interphase nuclei utilizing a telomere-specific peptide nucleic acid probe to assess telomeric signal intensity. The relative telomere length was presented as ratio (%) between each lesion and its normal control.
Results: Relative telomere lengths for urothelial carcinoma with inverted growth, inverted papilloma, and cystitis glandularis were 27%, 89%, and 93%, respectively. A statistically significant reduction in relative telomere length between urothelial carcinoma with inverted growth and inverted papilloma was present (p<0.001), while no significant difference was detected between normal urothelium, and cystitis glandularis, and inverted papilloma.
Conclusions: Significant telomere shortening in urothelial carcinoma with inverted growth compared to inverted papilloma contrasts the two lesions and supports the notion that inverted papilloma is a benign neoplasm. Despite the morphologic similarities of the two lesions, they may not share a common pathogenetic mechanism of development. Our findings also suggest telomere FISH may be useful biomarker in distinguishing inverted papilloma from urothelial carcinoma with inverted growth.
Category: Genitourinary (including renal tumors)
Monday, March 19, 2012 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 132, Monday Morning