Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma.
BACKGROUND
Identification of the type of human papillomavirus (HPV) by polymerase chain reaction and sequencing to determine coinfection or superinfection (by more than 1 HPV type) and other molecular events have not been reported in a series of patients exhibiting the morphologic spectrum of recurrent respiratory papillomatosis progressing to carcinoma.


METHODS
Four cases of juvenile-onset recurrent respiratory papillomatosis progressing to carcinoma (no history of smoking or irradiation in 2 cases) were studied. Morphologically distinct foci (squamous papilloma, pulmonary papillomatosis, squamous dysplasia subjacent to carcinoma, and squamous carcinoma) were subjected to laser capture microdissection and polymerase chain reaction amplification using general primers in addition to type-specific primers for HPV types 16 and 18. Direct sequencing of polymerase chain reaction products identified the type of HPV. The tissue sections were immunostained using antibodies to p53, pRb, p21(WAF1), and p16 proteins with a semiquantitative assessment.


RESULTS
Human papillomavirus 11 was the only type of HPV identified in all lesions of all cases associated with recurrent respiratory papillomatosis. There was a marked increase in p53 protein expression in foci of dysplasia and carcinoma as compared to squamous papilloma and pulmonary papillomatosis. An inverse correlation between p53 and p21(WAF1) protein expression was noted in all lesions. pRb protein expression increased from the benign to the malignant end of the spectrum. p16 protein was expressed in all lesions.


CONCLUSIONS
Infection by HPV-11 may be an early event associated with progression of recurrent respiratory papillomatosis to carcinoma. Increased expression of p53 and pRb proteins and a reduced expression of p21(WAF1) protein appear to be significant subsequent events.
Lele
Subodh M
SM
Department of Pathology, University of Kentucky College of Medicine, Lexington 40536, USA. slele2@uky.edu
Pou
Anna M
AM
Ventura
Karyna
K
Gatalica
Zoran
Z
Payne
Deborah
D
D000293:Adolescent; D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis; D018450:Disease Progression; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D009364:Neoplasm Recurrence, Local / Q000473:pathology* / Q000821:virology; D010212:Papilloma / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D027383:Papillomaviridae / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014412:Tumor Virus Infections / Q000150:complications / Q000378:metabolism / Q000473:pathology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004273:DNA, Neoplasm; D004279:DNA, Viral; D016159:Tumor Suppressor Protein p53