Lele Subodh M, Pou Anna M, Ventura Karyna, Gatalica Zoran, Payne Deborah
Department of Pathology, University of Kentucky College of Medicine, Lexington 40536, USA.
Arch Pathol Lab Med. 2002 Oct;126(10):1184-8. doi: 10.5858/2002-126-1184-MEITPO.
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.
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.
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.
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.
通过聚合酶链反应和测序鉴定人乳头瘤病毒（HPV）类型，以确定合并感染或重叠感染（由一种以上HPV型别引起）以及其他分子事件，尚未在一系列呈现复发性呼吸道乳头状瘤病形态学谱系并进展为癌的患者中报道。
研究了4例青少年起病的复发性呼吸道乳头状瘤病进展为癌的病例（2例无吸烟或放疗史）。对形态学上不同的病灶（鳞状乳头状瘤、肺乳头状瘤病、癌旁鳞状发育异常和鳞状癌）进行激光捕获显微切割，并使用通用引物以及针对HPV 16和18型的型特异性引物进行聚合酶链反应扩增。对聚合酶链反应产物进行直接测序以鉴定HPV类型。使用针对p53、pRb、p21（WAF1）和p16蛋白的抗体对组织切片进行免疫染色，并进行半定量评估。
HPV 11是在所有与复发性呼吸道乳头状瘤病相关的病例的所有病灶中鉴定出的唯一HPV型别。与鳞状乳头状瘤和肺乳头状瘤病相比，发育异常和癌病灶中p53蛋白表达明显增加。在所有病灶中均观察到p53和p21（WAF1）蛋白表达呈负相关。pRb蛋白表达从谱系的良性端到恶性端增加。p16蛋白在所有病灶中均有表达。
HPV - 11感染可能是与复发性呼吸道乳头状瘤病进展为癌相关的早期事件。p53和pRb蛋白表达增加以及p21（WAF1）蛋白表达降低似乎是重要的后续事件。
