Significance of DNA Ploidy and Cell Proliferation in Juvenile Respiratory Papillomatosis

Abstract

The clinical course of recurrent respiratory papillomatosis (RRP) in children is variable and unpredictable. At present there is no way to identify patients at risk for aggressive disease. The objective of this study was to evaluate whether DNA ploidy and cell proliferation analyses can predict the clinical course in children with RRP. Two different methods of estimating proliferation activity were compared. Nonembedded papilloma biopsy specimens from 18 pediatric patients were analyzed by flow cytometry providing DNA content with cell cycle analysis. The expression of the proliferative marker Ki-67 in papilloma tissue was quantified by immunohistochemistry. The patients were prospectively observed for 12 to 18 months. DNA content analysis and Ki-67 expression were compared to clinical information regarding number of disease sites, distal tracheobronchial spread, number of recurrences, need for tracheostomy, and disease remission. High S-phase fraction, proliferative index, and Ki-67 expression correlated with an aggressive clinical course. DNA ploidy analysis and immunodetection of proliferative markers may assist in predicting prognosis in children with RRP.

Keywords

children DNA content Ki-67 papilloma

Get full access to this article

View all access options for this article.

References

Jones

Myers

. Benign neoplasms of the larynx. Otolaryngol Clin North Am 1985; 17: 157–78.

Quiney

Hall

Croft

. Laryngeal papillomatosis revisited; analysis of 113 patients. Clin Otolaryngol 1989; 14: 217–25.

Nikolaidis

Trost

Buchholz

Wilkinson

. The relationship of histologic and clinical factors in laryngeal papillomatosis. Arch Pathol Lab Med 1985; 109: 24–9.

Lindeberg

. Laryngeal papillomas: Histomorphometric evaluation of multiple and solitary lesions. Clin Otolaryngol 1991; 16: 257–60.

Abramson

Steinberg

Winkler

. Laryngeal papillomatosis: Clinical histopathologic and molecular studies. Laryngoscope 1987; 97: 678–85.

Mounts

Kashima

. Association of human papilloma virus subtype and clinical course in respiratory papillomatosis. Laryngoscope 1984; 94: 28–33.

Pou

Rimell

Jordan

. Adult respiratory papillomatosis: Human papillomavirus type and viral coin-fections as predictors of prognosis. Ann Otol Rhinol Laryngol 1995; 104: 758–62.

Sigurdsson

Baldetorp

Borg

. Indicators of prognosis in node-negative breast cancer. N Engl J Med 1990; 322: 1045–53.

Gerdes

Lemp

Baisch

Wacker

Schwab

Stein

. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984; 133: 1710–5.

10.

Rose

Maddox

Brown

. Which proliferation markers for routine immunohistology? A comparison of five antibodies. J Clin Pathol 1994; 47: 18–22.

11.

Palutke

Tabaczka

Kukwruga

Kantor

. A method of measuring lymphocyte proliferation in mixed lymphocyte cultures using a nuclear proliferation antigen, Ki-67 and flow cytometry. Am J Clin Pathol 1989; 91: 417–21.

12.

Vindelon

Christensen

Nissen

. A detergent-trypsin method for preparation of nuclei for flow cytometric DNA analysis. Cytometry 1983; 3: 323–7.

13.

Rabinovitch

. Numerical compensation for the effects of cell clumping on DNA content histograms [Abstract]. Cytometry Suppl 1990(suppl 4): 27.

14.

Dean

Jett

. Mathematical analysis of DNA distribution derived from flow microfluorimetry. J Cell Biol 1974; 4: 523–7.

15.

Maquardt

. An algorithm for least-squares estimation of nonlinear parameters. Soc Ind Appl Math 1963; 11: 431–41.

16.

Vindelon

Christensen

Nissen

. Standardization of high resolution flow cytometry DNA analysis by the simultaneous use of chicken and trout red blood cells as internal reference standards. Cytometry 1983; 3: 328–31.

17.

Rabinovitch

. Practical consideration for DNA content and cell cycle analysis. In: Bauer

Duque

Shankey

, eds. Clinical flow cytometry: principles and application. Baltimore, Md: Williams & Wilkins, 1993: 117–42.

18.

Copete

Wendt

Chen

. Expression of p53, Ki-67 and cytokeratin-4 (CK4) in oral papillomas. J Oral Pathol Med 1997; 26: 211–6.

19.

McCormick

Chang

Hobbs

Datta

Hall

. Detection of the Ki-67 antigen in fixed and wax-embedded sections with the monoclonal antibody MIB1. Histopathology 1993; 22: 355–60.

20.

Chiang

Ustav

Stenlund

Broker

Chow

. Viral E1 and E2 proteins support replication of homologous and heterologous papillomaviral origins. Proc Natl Acad Sci U S A 1992; 89: 5799–803.

21.

Del Vecchio

Romanczuk

Howley

Baker

. Transient replication of human papillomavirus DNA. J Virol 1992; 66: 5949–58.

22.

Stoler

Wolinsky

Whitbeck

Broker

Chow

. Differentiation linked human papillomavirus types 6 and 11 transcription in genital condylomata revealed by in situ hybridization with message-specific RNA probes. Virology 1989; 172: 331–40.

23.

Munger

Werness

Pyson

Harlow

Homley

. Complex formation of human papillomavirus E7 proteins with the retinoblastoma tumor suppressor gene product. EMBO J 1989; 8: 4099–105.

24.

Crook

Tidy

Vousden

. Degradation of p53 can be targeted by HPV sequences distinct from those required for p53 binding and trans-activation. Cell 1987; 67: 547–56.