Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract

Matthias Eiber, Johanna M M Van Oers, Ellen C. Zwarthoff, Theo H. Van Der Kwast, Oehler Ulrich, Burkhard Helpap, Stephan Stoerkel, Hagen Blaszyk, John Cheville, Guido Sauter, Peter J. Wild, Robert Stoehr, Ferdinand Hofstaedter, Arndt Hartmann

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

AIM: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish from noninvasive urothelial carcinoma with prominent inverted growth pattern (invNIUC). Ancillary markers may help to resolve such cases and clarify the reported malignant potential of some IPs. METHODS: Eighty-nine urothelial lesions initially diagnosed as IP were reviewed by 4 experienced urologic pathologists and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6). Mutations of the FGFR3 gene, deletions (loss of heterozygosity) of 9p, 9q, and 17p, microsatellite instability, and elevated microsatellite instability at selected tetranucleotides were also analyzed. RESULTS: Considerable interobserver variability in histopathologic diagnoses was noticed. Only 62 (69.7%) initial diagnoses were confirmed by the review pathologists whereas 23 tumors (25.8%) were redefined as invNIUC. Molecular analyses revealed infrequent alterations in IPs, including microsatellite instability (1.8%), elevated microsatellite instability at selected tetranucleotides (13.2%), FGFR3 mutations (9.8%), 9p deletions (3.9%), 9q deletions (13.2%), 17p deletions (5.1%), nuclear p53 accumulation (18.9%), and aberrant immunostaining for MSH2 (5.8%), MLH1 (11.8%), and MSH6 (3.8%). IP and invNIUC differed in FGFR3 mutations and Ki-67 labeling index (P<0.001 each), and 9q loss of heterozygosity (P=0.03). There were fewer recurrences in IP (5.4%) compared with invNIUC (40.9%; P<0.0001). CONCLUSIONS: IP is a benign lesion that lacks specific genetic alterations found in exophytic noninvasive papillary urothelial tumors. These lesions could be reactive in nature, perhaps secondary to chronic inflammation or a neoplastic process that lack specific genetic alterations. Nevertheless given the clinical and molecular data of this study a conservative clinical approach is appropriate.

Original languageEnglish (US)
Pages (from-to)938-946
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume31
Issue number6
DOIs
StatePublished - Jun 2007

Fingerprint

Inverted Papilloma
Urinary Tract
Microsatellite Instability
Recurrence
Loss of Heterozygosity
Neoplasms
Mutation
Neoplastic Processes
Observer Variation
Gene Deletion
Inflammation
Carcinoma
Growth

Keywords

  • FGFR3
  • Inverted papilloma
  • Inverted urothelial carcinoma
  • mib-1
  • Molecular markers

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Eiber, M., Van Oers, J. M. M., Zwarthoff, E. C., Van Der Kwast, T. H., Ulrich, O., Helpap, B., ... Hartmann, A. (2007). Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract. American Journal of Surgical Pathology, 31(6), 938-946. https://doi.org/10.1097/01.pas.0000249448.13466.75

Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract. / Eiber, Matthias; Van Oers, Johanna M M; Zwarthoff, Ellen C.; Van Der Kwast, Theo H.; Ulrich, Oehler; Helpap, Burkhard; Stoerkel, Stephan; Blaszyk, Hagen; Cheville, John; Sauter, Guido; Wild, Peter J.; Stoehr, Robert; Hofstaedter, Ferdinand; Hartmann, Arndt.

In: American Journal of Surgical Pathology, Vol. 31, No. 6, 06.2007, p. 938-946.

Research output: Contribution to journalArticle

Eiber, M, Van Oers, JMM, Zwarthoff, EC, Van Der Kwast, TH, Ulrich, O, Helpap, B, Stoerkel, S, Blaszyk, H, Cheville, J, Sauter, G, Wild, PJ, Stoehr, R, Hofstaedter, F & Hartmann, A 2007, 'Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract', American Journal of Surgical Pathology, vol. 31, no. 6, pp. 938-946. https://doi.org/10.1097/01.pas.0000249448.13466.75
Eiber, Matthias ; Van Oers, Johanna M M ; Zwarthoff, Ellen C. ; Van Der Kwast, Theo H. ; Ulrich, Oehler ; Helpap, Burkhard ; Stoerkel, Stephan ; Blaszyk, Hagen ; Cheville, John ; Sauter, Guido ; Wild, Peter J. ; Stoehr, Robert ; Hofstaedter, Ferdinand ; Hartmann, Arndt. / Low frequency of molecular changes and tumor recurrence in inverted papillomas of the urinary tract. In: American Journal of Surgical Pathology. 2007 ; Vol. 31, No. 6. pp. 938-946.
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abstract = "AIM: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish from noninvasive urothelial carcinoma with prominent inverted growth pattern (invNIUC). Ancillary markers may help to resolve such cases and clarify the reported malignant potential of some IPs. METHODS: Eighty-nine urothelial lesions initially diagnosed as IP were reviewed by 4 experienced urologic pathologists and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6). Mutations of the FGFR3 gene, deletions (loss of heterozygosity) of 9p, 9q, and 17p, microsatellite instability, and elevated microsatellite instability at selected tetranucleotides were also analyzed. RESULTS: Considerable interobserver variability in histopathologic diagnoses was noticed. Only 62 (69.7{\%}) initial diagnoses were confirmed by the review pathologists whereas 23 tumors (25.8{\%}) were redefined as invNIUC. Molecular analyses revealed infrequent alterations in IPs, including microsatellite instability (1.8{\%}), elevated microsatellite instability at selected tetranucleotides (13.2{\%}), FGFR3 mutations (9.8{\%}), 9p deletions (3.9{\%}), 9q deletions (13.2{\%}), 17p deletions (5.1{\%}), nuclear p53 accumulation (18.9{\%}), and aberrant immunostaining for MSH2 (5.8{\%}), MLH1 (11.8{\%}), and MSH6 (3.8{\%}). IP and invNIUC differed in FGFR3 mutations and Ki-67 labeling index (P<0.001 each), and 9q loss of heterozygosity (P=0.03). There were fewer recurrences in IP (5.4{\%}) compared with invNIUC (40.9{\%}; P<0.0001). CONCLUSIONS: IP is a benign lesion that lacks specific genetic alterations found in exophytic noninvasive papillary urothelial tumors. These lesions could be reactive in nature, perhaps secondary to chronic inflammation or a neoplastic process that lack specific genetic alterations. Nevertheless given the clinical and molecular data of this study a conservative clinical approach is appropriate.",
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AU - Van Oers, Johanna M M

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AU - Ulrich, Oehler

AU - Helpap, Burkhard

AU - Stoerkel, Stephan

AU - Blaszyk, Hagen

AU - Cheville, John

AU - Sauter, Guido

AU - Wild, Peter J.

AU - Stoehr, Robert

AU - Hofstaedter, Ferdinand

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N2 - AIM: Inverted papilloma (IP) of the urinary tract can be difficult to distinguish from noninvasive urothelial carcinoma with prominent inverted growth pattern (invNIUC). Ancillary markers may help to resolve such cases and clarify the reported malignant potential of some IPs. METHODS: Eighty-nine urothelial lesions initially diagnosed as IP were reviewed by 4 experienced urologic pathologists and studied immunohistochemically (Ki67, p53, CK20, MSH2, MLH1, and MSH6). Mutations of the FGFR3 gene, deletions (loss of heterozygosity) of 9p, 9q, and 17p, microsatellite instability, and elevated microsatellite instability at selected tetranucleotides were also analyzed. RESULTS: Considerable interobserver variability in histopathologic diagnoses was noticed. Only 62 (69.7%) initial diagnoses were confirmed by the review pathologists whereas 23 tumors (25.8%) were redefined as invNIUC. Molecular analyses revealed infrequent alterations in IPs, including microsatellite instability (1.8%), elevated microsatellite instability at selected tetranucleotides (13.2%), FGFR3 mutations (9.8%), 9p deletions (3.9%), 9q deletions (13.2%), 17p deletions (5.1%), nuclear p53 accumulation (18.9%), and aberrant immunostaining for MSH2 (5.8%), MLH1 (11.8%), and MSH6 (3.8%). IP and invNIUC differed in FGFR3 mutations and Ki-67 labeling index (P<0.001 each), and 9q loss of heterozygosity (P=0.03). There were fewer recurrences in IP (5.4%) compared with invNIUC (40.9%; P<0.0001). CONCLUSIONS: IP is a benign lesion that lacks specific genetic alterations found in exophytic noninvasive papillary urothelial tumors. These lesions could be reactive in nature, perhaps secondary to chronic inflammation or a neoplastic process that lack specific genetic alterations. Nevertheless given the clinical and molecular data of this study a conservative clinical approach is appropriate.

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