p16INK4a expression correlates with degree of cervical neoplasia:: A comparison detection of high-risk with Ki-67 expression and HPV types

被引:186
作者
Agoff, SN
Lin, P
Morihara, J
Mao, C
Kiviat, NB
Koutsky, LA
机构
[1] Univ Washington, Med Ctr, Harborview Med Ctr, Dept Pathol, Seattle, WA 98195 USA
[2] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA
[3] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA
关键词
cervical neoplasia; HPV; Ki-67; p16(INK4a);
D O I
10.1097/01.MP.0000077518.78046.0C
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Although recent studies have suggested that p16(INK4a) may be a useful surrogate biomarker of cervical neoplasia, Ki-67 and human papillomavirus testing have also been shown to be useful in detecting neoplasia. To help delineate the utility of p16(INK4a), biopsy samples (n = 569: negative, 133; reactive, 75; atypical, 39; low grade, 76; moderate, 80; and severe intraepithelial neoplasia, 113; also, squamous cell carcinoma, 46; adenocarcinoma, 7) were analyzed by immunohistochemistry for expression of p16(INK4a) and Ki-67 (n = 432), as well as by in situ hybridization for human papillomavirus Type 16 (n = 219). Testing for high-risk human papillomavirus types by polymerase chain reaction and HybridCapture2 was performed on concurrent cervical swab specimens. Recuts of the original blocks were reexamined (n = 198). Endometrial biopsies (n = 10) were also analyzed for p16(INK4a) expression. Degree of p16(INK4a) and Ki-67 expression correlated with degree of cervical neoplasia (P<.001) and with presence of high-risk human papillomavirus types (P<.001). There was no relationship between p16(INK4a) overexpression and inflammation or hormonal status. Ki-67 expression correlated with inflammation (P = 0.003) and was expressed in more reactive and atypical lesions than p16(INK4a) (p = 0.008). Probes for human papillomavirus 16 stained 54% of cervical neoplastic lesions; the degree of staining correlated significantly with degree of neoplasia (P<.001) and p16(INK4a) staining (p<.001). Interobserver reproducibility was substantial for p16(INK4a) and Ki-67 interpretation (weighted kappa: 0.74 and 0.70, respectively). Expression of p16(INK4a) was observed in all endometrial biopsies. Compared with Ki-67 expression and detection of high-risk human papillomavirus, p16(INK4a) was less likely to be positive in samples from women with negative, reactive, and atypical biopsies. Although expression of p16(INK4a) in endometrial epithelium may be problematic in terms of screening, the potential of p16(INK4a) as a screening test warrants investigation.
引用
收藏
页码:665 / 673
页数:9
相关论文
共 27 条
  • [11] Koutsky LA, 2000, J NATL CANCER I, V92, P397, DOI 10.1093/jnci/92.5.397
  • [12] Kruse AJ, 2001, J PATHOL, V193, P48
  • [13] Evaluation of human papillomavirus testing in primary screening for cervical abnormalities - Comparison of sensitivity, specificity, and frequency of referral
    Kulasingam, SL
    Hughes, JP
    Kiviat, NB
    Mao, C
    Weiss, NS
    Kuypers, JM
    Koutsky, LA
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 288 (14): : 1749 - 1757
  • [14] Lin P, 2001, CANCER EPIDEM BIOMAR, V10, P1037
  • [15] HUMAN PAPILLOMAVIRUS INFECTION OF THE CERVIX - RELATIVE RISK ASSOCIATIONS OF 15 COMMON ANOGENITAL TYPES
    LORINCZ, AT
    REID, R
    JENSON, AB
    GREENBERG, MD
    LANCASTER, W
    KURMAN, RJ
    [J]. OBSTETRICS AND GYNECOLOGY, 1992, 79 (03) : 328 - 337
  • [16] Luo YHV, 2002, ARCH PATHOL LAB MED, V126, P1205
  • [17] Identifying women with cervical neoplasia - Using human papillomavirus DNA testing for equivocal Papanicolaou results
    Manos, MM
    Kinney, WK
    Hurley, LB
    Sherman, ME
    Shieh-Ngai, J
    Kurman, RJ
    Ransley, JE
    Fetterman, BJ
    Hartinger, JS
    McIntosh, KM
    Pawlick, GF
    Hiatt, RA
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1999, 281 (17): : 1605 - 1610
  • [18] P16/MTS1 and pRB expression in endometrial carcinomas
    Milde-Langosch, K
    Riethdorf, L
    Bamberger, AM
    Löning, T
    [J]. VIRCHOWS ARCHIV-AN INTERNATIONAL JOURNAL OF PATHOLOGY, 1999, 434 (01): : 23 - 28
  • [19] Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation
    Nakao, Y
    Yang, X
    Yokoyama, M
    Ferenczy, A
    Tang, SC
    Pater, MM
    Pater, A
    [J]. BRITISH JOURNAL OF CANCER, 1997, 75 (10) : 1410 - 1416
  • [20] Comparison of PCR- and hybrid capture-based human papillomavirus detection systems using multiple cervical specimen collection strategies
    Peyton, CL
    Schiffman, M
    Lörincz, AT
    Hunt, WC
    Mielzynska, I
    Bratti, C
    Eaton, S
    Hildesheim, A
    Morera, LA
    Rodriguez, AC
    Herrero, R
    Sherman, ME
    Wheeler, CM
    [J]. JOURNAL OF CLINICAL MICROBIOLOGY, 1998, 36 (11) : 3248 - 3254