title: Nested variant of urothelial carcinoma: a clinicopathologic and immunohistochemical study of 12 cases.
abstract: Nested variant of urothelial carcinoma is characterized by confluent small nests and abortive tubules of mildly atypical neoplastic cells infiltrating the lamina propria and/or muscularis propria of the bladder. Despite its deceptively bland histomorphologic appearance, the lesion is reported to have an aggressive behavior. The collective immunohistochemical expression of suppressor genes, growth factor, and proliferation activity marker has not been previously studied in this disease. Formalin-fixed, paraffin-embedded archival tissues from 12 cases of nested variant of urothelial carcinoma were stained with monoclonal antibodies to p21, p27, p53, EGF-R, and bcl-2, as well as the proliferation marker MIB-1. The area of predominant immunoreactivity was also evaluated. The pattern of immunostaining was compared with the clinical parameters. p21 was positive in 10 of 12 cases and located at the deepest portion of the tumor in 5 of 10 positive cases. Immunoreactivity for p27 was seen in 11 of 12 cases and limited to the superficial portion of the tumor in 9 of 11 positive cases. Only 3 and 2 of 12 cases were positive for p53 and bcl-2, respectively. MIB-1 immunoreactivity ranged from 2 to 35% of the neoplastic cells, with most tumors showing a proliferation index of >15%. Follow-up ranged from 3 to 30 months (mean, 17.6 mo). All patients except one were alive, although three patients developed metastases. Nested variant of urothelial carcinoma is a deceptively benign-appearing neoplasm with potential of deep invasion and metastases. Immunohistochemically, nested variant of urothelial carcinoma shares some features with high-risk conventional urothelial carcinomas, such as loss of p27 expression and high proliferation index. Nevertheless, p53, bcl-2, or EGF-r immunoreactivity is not frequently seen.
authors.affiliation: Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. lino@mskcc.org
authors.forename: Oscar
authors.initials: O
authors.lastname: Lin
authors.forename: Marina
authors.initials: M
authors.lastname: Cardillo
authors.forename: Guido
authors.initials: G
authors.lastname: Dalbagni
authors.forename: Irina
authors.initials: I
authors.lastname: Linkov
authors.forename: Brian
authors.initials: B
authors.lastname: Hutchinson
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000032:analysis; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019394:Ki-67 Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D066246:ErbB Receptors