Expression of retinoblastoma gene product in respiratory epithelium and sinonasal neoplasms: relationship with p16 and cyclin D1 expression
M.J. Schwerer1, A. Sailer1, K. Kraft1, K. Baczako2 and H. Maier3
1Department of Pathology, Military Hospital Ulm, Ulm/Donau,
Germany, 2Institute of Pathology, Ulm/Donau, Germany and 3Department
of Otorhinolaryngology, Head and Neck Surgery, Military Hospital
Ulm, Ulm/Donau, Germany
Offprint requests to: Michael
J. Schwerer, MD, Department of Pathology, Military Hospital Ulm,
Oberer Eselsberg 40, D-89081 Ulm/Donau, Germany. Fax: +49 731
1710 2028. e-mail: michael.schwerer@t-online.de
Summary. Transition from G1 to S phase of the cell cycle
is mediated by interactions between the Retinoblastoma gene product
(pRb), p16, and cyclin D1. To determine the expression of these
proteins in the sinonasal mucosa immunohistochemistry was carried
out on archived tissue sections from 46 patients (37 men, 9 women,
age range 17 to 82 years, median 55 years). Nuclear immunostaining
for these proteins was assessed and the expression rates (percentages
of immunoreactive nuclei) in normal respiratory epithelium, inverted
sinonasal papillomas, cylindrical (oncocytic) sinonasal papillomas,
and squamous cell carcinomas were compared.
Normal respiratory epithelium showed significantly higher pRb
expression in surface cells compared to basal cells (p<0.05).
In contrast, abundant pRb expression in surface and basal cells
was detected in columnar differentiation in sinonasal papillomas
and adjacent mucosa. Cuboidal and squamous metaplasia in inverted
papillomas showed significantly reduced pRb expression in surface
cells compared to columnar epithelium in inverted papillomas (p<0.05,
respectively). Expression of p16 was detected in all epithelial
cell layers of normal respiratory epithelium, sinonasal papillomas,
and adjacent mucosa. Cuboidal and squamous metaplasia in inverted
papillomas showed increased p16 expression in surface cells compared
to columnar epithelium in inverted papillomas (p<0.05 between
squamous metaplasia and columnar epithelium). Sinonasal squamous
cell carcinomas showed the coexpression of pRb and p16. Expression
rates of cyclin D1 higher than 10% were detected only in invasive
carcinomas but not in carcinoma in situ, sinonasal papillomas
or respiratory epithelium. Conclusively, pRb expression accompanies
terminal differentiation in columnar surface cells. Expression
of pRb in proliferating basal cells is present in sinonasal papillomas
and adjacent mucosa but not in normal respiratory epithelium.
Cuboidal and squamous metaplasia in inverted papillomas involves
downregulation of pRb expression along with increased p16 expression
in surface cells. Sinonasal squamous cell carcinomas coexpress
pRb and p16. Overexpression of cyclin D1 in sinonasal lesions
is confined to invasive squamous cell carcinomas. Histol. Histopathol.
18, 143-151 (2003)
Key words: Respiratory epithelium, Sinonasal lesions,
pRb, P16, Cyclin D1
DOI: 10.14670/HH-18.143