Inverted papilloma of the urinary bladder: a molecular genetic appraisal

Abstract

Inverted papilloma of urinary bladder is an uncommon urothelial neoplasm. Its relationship to urothelial carcinoma is controversial. Little is known of the genetic abnormalities of inverted papilloma. To better understand its genetics, we analyzed 39 inverted papillomas, including 36 from men and three from women, for loss of heterozygosity (LOH). We examined four polymorphic microsatellite markers located on chromosome 9q32-33(D9S177), chromosome 9p22 (IFNA), chromosome 3p14.2 (D3S1300) and chromosome 17p13.1 (TP53), where genetic alterations occur frequently in urothelial carcinomas. Additionally, the status of inactivation of X-chromosome was examined in three female patients. The frequency of LOH in informative cases was 8% (3 of 37) for D9S177, 10% (4 of 38) for TP53, 8% (3 of 37) for IFNA and 8% (3 of 36) for D3S1300. In the analysis of X-chromosome inactivation, all three cases yielded informative results and one had nonrandom inactivation of X-chromosomes. The monoclonal origin demonstrated in the study of X-chromosome inactivation indicates the clonal process of inverted papilloma; however, the low incidence of LOH supports the view that inverted papilloma in urinary bladder is a benign neoplasm with molecular genetic abnormalities different from those of urothelial carcinoma.

Unique clinicopathologic and molecular characteristics of urinary bladder tumors in children and young adults

“…Tumors may be subdivided into trabecular and glandular variants; the latter is characterized by pseudoglandular urothelial-lined spaces or even true mucicarmine-positive secreting cells [53], and is remarkably difficult to distinguish from florid cystitis glandularis. Nonrandom X-chromosome inactivation studies have found inverted papilloma to be a clonal neoplasm arising from a single progenitor cell [60]. The incidence of LOH in inverted papilloma (8%-10%) is low compared to that of UC (29%-80%) [61][62][63][64][65][66], and the frequency of allelic loss in inverted papilloma is similar to that of normal urothelium [67], suggesting that inverted papilloma and UC arise through separate and distinct pathogenetic mechanisms.…”

Molecular pathogenesis of bladder cancer

“…Infrequent LOH on 3p (8%), 9p (8%), 9q (8%), and 17p (10%) was found in a study of 39 inverted papillomas. 103 A second study, of 62 inverted papillomas, found infrequent FGFR3 mutation (9.8%) and LOH of chromosome 9 (3.9% on 9p and 13.2% on 9q). 104 In the same study, inverted growth pattern urothelial carcinomas showed higher frequencies of alterations (83.1% FGFR3 mutation; 36.4% 9q LOH), indicating that inverted papillomas are distinct from urothelial papilloma and are not obviously related to carcinomas with an inverted growth pattern.…”

Androgen replacement therapy contributes to improving lower urinary tract symptoms in patients with hypogonadism and benign prostate hypertrophy: a randomised controlled study

“…This type of tumor is characterized pathologically by inverted growth of transitional epithelia with no atypia. Generally, inverted papilloma occurs more frequently in men than in women, and the most common target age is 30 to 60 years old, which is younger than bladder cancer [Sung et al, 2006b]. Although the etiological factors associated with inverted papilloma have not been 5 established, HPV-DNA has been detected in some cases of inverted papilloma [Chan et al, 1997].…”

“…Inverted papilloma is a rare benign urothelial tumor that develops predominantly in the bladder, and accounts for less than 1% of all urothelial neoplasms [Sung et al, 2006b]. This type of tumor is characterized pathologically by inverted growth of transitional epithelia with no atypia.…”