caa a22 4500 397561180 CHVBK 20180308164816.0 cr unu---uuuuu 161202e19960320xx s 000 0 eng 10.1093/jnci/88.6.355 doi (NATIONALLICENCE)oxford-10.1093/jnci/88.6.355 Association Between Human Papillomavirus Type and Clonal Status of Cervical Squamous Intraepithelial Lesions [Elektronische Daten] [Tjoung Won Park, Ralph M. Richart, Xiao-Wei Sun, Thomas C. Wright] Background: Lesions that are histologically classified as precursors of cervical cancer, which are often referred to as squamous intraepithelial lesions (SILs), represent a heterogeneous clinical entity that can be associated with many different types of human papillomaviruses (HPVs) and have a variable biologic behavior. Approximately one half of low-grade SILs behave as non-neoplastic, productive viral lesions that frequently regress spontaneously, whereas the other half behave as neoplasms and either persist or progress to a histologically higher grade lesion. Identification of biomarkers that reliably differentiate those low-grade SILs with the properties of a non-neoplastic viral infection from those with the properties of neoplasia would provide a more rational basis for decisions about disease management. Since monoclonality is a hallmark of neoplasia irrespective of organ site, clonal status might represent one such biomarker. Purpose: To better understand the pathobiology of SILs, we analyzed the clonality of low-grade and high-grade SILs and compared their clonal status with their associated HPV types. Methods: One hundred forty formalin-fixed, paraffin-embedded cervical biopsy and loop electrosurgical specimens, originally diagnosed as SILs, were obtained from the pathology archives of both the Columbia Presbyterian Medical Center and Kyto Diagnostics in New York. Clonality was determined with the use of a polymerase chain reaction (PCR) based method that detects nonrandom X-chromosome inactivation. This PCR-method amplifies a polymorphic region of the androgen receptor gene that is flanked by several differentially methylated enzyme sites. The same tissue was also analyzed for HPV DNA with the use of PCR and both L1 and E6 "consensus” primers. Results: All 25 evaluable cases of high-grade SILs were determined to be monoclonal. Although 54 (68%) of 79 evaluable low-grade SILs were monoclonal, 25 (32%) of 79 low-grade SILs were polyclonal. A strong association was observed between HPV type and clonal status, with a total of 71 (47 low-grade and 24 high-grade) SILs determined to be monoclonal and containing HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. In contrast, 22 (92%) of the 24 low-grade SILs that contained another type of HPV were polyclonal (Fisher's exact test, two-sided, P≤.001). Conclusions: Our findings suggest that the histopathologic entity termed low-grade SIL consists of two different types of lesions that are biologically distinct. One lesion is monoclonal and is associated with HPV types 16, 18, 31, 33, 35, 39, 45, 56, 58, or 65. The second type of low-grade SIL is polyclonal and is associated with other types of HPV. [J Natl Cancer Inst 1996;88:355-8] © Oxford University Press REPORTS nationallicence Park Tjoung Won Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut Richart Ralph M. Departments of Pathology and Obstetrics and Gynecology, College of Physicians and Surgeons of Columbia University New York, NY aut Sun Xiao-Wei Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut Wright Thomas C. Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut JNCI: Journal of the National Cancer Institute Oxford University Press 88/6(1996-03-20), 355-358 0027-8874 88:6<355 1996 88 jnci https://doi.org/10.1093/jnci/88.6.355 text/html Onlinezugriff via DOI 1 other jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jnci/88.6.355 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Park Tjoung Won Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut NATIONALLICENCE 700 1- Richart Ralph M. Departments of Pathology and Obstetrics and Gynecology, College of Physicians and Surgeons of Columbia University New York, NY aut NATIONALLICENCE 700 1- Sun Xiao-Wei Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut NATIONALLICENCE 700 1- Wright Thomas C. Department of Pathology, College of Physicians and Surgeons of Columbia University New York, NY aut NATIONALLICENCE 773 0- JNCI: Journal of the National Cancer Institute Oxford University Press 88/6(1996-03-20), 355-358 0027-8874 88:6<355 1996 88 jnci Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford