Logo of jclinpathJournal of Clinical PathologyVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Clin Pathol. 1999 Dec; 52(12): 880–887.
PMCID: PMC501653

Cyclin dependent kinase inhibitor p27Kip1 expression in normal and neoplastic cervical epithelium.


AIM: To investigate whether there is loss of the p27Kip1 protein in developing cervical cancer and whether p27Kip1 immunoreactivity has any relation to the proliferative indicator Ki-67. METHODS: The expression of p27Kip1 and Ki-67 was assessed by immunohistochemistry in serial sections from normal epithelium (13), low grade (27) and high grade (19) squamous intraepithelial lesions (LSIL, HSIL), and invasive cervical cancer (23). In the SIL cases the presence of human papillomavirus (HPV) genomic sequences was assessed by in situ hybridisation. The results were evaluated by image analysis, and reported as mean score of the percentage of p27Kip1 and of Ki-67 positive cells in each histological group. RESULTS: In general, p27Kip1 immunostaining was related to squamous differentation, and was intense in normal epithelium (47%), while it was reduced in SIL lesions as an effect of the decreased number of differentiating cells. However, decrease in the p27Kip1 expression was more evident in LSIL (36%) than in HSIL (39%); in the latter, p27Kip1 had a different intraepithelial distribution in that the staining extended to the basal cells. The average levels of p27Kip1 were similar in SIL lesions associated to low, intermediate, and high risk HPV types. Compared with normal epithelium and dysplasia, invasive cancer showed significantly lower p27Kip1 levels (23%). There was no relation between p27Kip1 and Ki-67 labelling indices in any of the histological groups examined. CONCLUSIONS: A reduction in p27Kip1 protein occurs in cervical cancer independently of the proliferative status. The changes in p27Kip1 expression may be related to the unregulated kinetics of developing cervical cancer.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (3.6M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Herrington CS. Human papillomaviruses and cervical neoplasia. II. Interaction of HPV with other factors. J Clin Pathol. 1995 Jan;48(1):1–6. [PMC free article] [PubMed]
  • Mitchell MF, Hittelman WN, Hong WK, Lotan R, Schottenfeld D. The natural history of cervical intraepithelial neoplasia: an argument for intermediate endpoint biomarkers. Cancer Epidemiol Biomarkers Prev. 1994 Oct-Nov;3(7):619–626. [PubMed]
  • Troncone G, Martinez JC, Palombini L, De Rosa G, Mugica C, Rodriguez JA, Zeppa P, Di Vizio D, Lucariello A, Piris MA. Immunohistochemical expression of mdm2 and p21WAF1 in invasive cervical cancer: correlation with p53 protein and high risk HPV infection. J Clin Pathol. 1998 Oct;51(10):754–760. [PMC free article] [PubMed]
  • Werness BA, Wang HQ, Chance J, Goldstein DJ. p53-independent expression of p21waf1/cip1 in preinvasive and invasive squamous neoplasms of the uterine cervix. Mod Pathol. 1997 Jun;10(6):578–584. [PubMed]
  • Schmidt-Grimminger DC, Wu X, Jian Y, Broker TR, Chow LT. Post-transcriptional induction of p21cip1 protein in condylomata and dysplasias is inversely related to human papillomavirus activities. Am J Pathol. 1998 Apr;152(4):1015–1024. [PMC free article] [PubMed]
  • Palazzo JP, Mercer WE, Kovatich AJ, McHugh M. Immunohistochemical localization of p21(WAF1/CIP1) in normal, hyperplastic, and neoplastic uterine tissues. Hum Pathol. 1997 Jan;28(1):60–66. [PubMed]
  • Polyak K, Lee MH, Erdjument-Bromage H, Koff A, Roberts JM, Tempst P, Massagué J. Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals. Cell. 1994 Jul 15;78(1):59–66. [PubMed]
  • Slingerland JM, Hengst L, Pan CH, Alexander D, Stampfer MR, Reed SI. A novel inhibitor of cyclin-Cdk activity detected in transforming growth factor beta-arrested epithelial cells. Mol Cell Biol. 1994 Jun;14(6):3683–3694. [PMC free article] [PubMed]
  • Polyak K, Kato JY, Solomon MJ, Sherr CJ, Massague J, Roberts JM, Koff A. p27Kip1, a cyclin-Cdk inhibitor, links transforming growth factor-beta and contact inhibition to cell cycle arrest. Genes Dev. 1994 Jan;8(1):9–22. [PubMed]
  • Coats S, Flanagan WM, Nourse J, Roberts JM. Requirement of p27Kip1 for restriction point control of the fibroblast cell cycle. Science. 1996 May 10;272(5263):877–880. [PubMed]
  • Steeg PS, Abrams JS. Cancer prognostics: past, present and p27. Nat Med. 1997 Feb;3(2):152–154. [PubMed]
  • Loda M, Cukor B, Tam SW, Lavin P, Fiorentino M, Draetta GF, Jessup JM, Pagano M. Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med. 1997 Feb;3(2):231–234. [PubMed]
  • Tan P, Cady B, Wanner M, Worland P, Cukor B, Magi-Galluzzi C, Lavin P, Draetta G, Pagano M, Loda M. The cell cycle inhibitor p27 is an independent prognostic marker in small (T1a,b) invasive breast carcinomas. Cancer Res. 1997 Apr 1;57(7):1259–1263. [PubMed]
  • Sánchez-Beato M, Sáez AI, Martínez-Montero JC, Sol Mateo M, Sánchez-Verde L, Villuendas R, Troncone G, Piris MA. Cyclin-dependent kinase inhibitor p27KIP1 in lymphoid tissue: p27KIP1 expression is inversely proportional to the proliferative index. Am J Pathol. 1997 Jul;151(1):151–160. [PMC free article] [PubMed]
  • Erickson LA, Jin L, Wollan PC, Thompson GB, van Heerden J, Lloyd RV. Expression of p27kip1 and Ki-67 in benign and malignant thyroid tumors. Mod Pathol. 1998 Feb;11(2):169–174. [PubMed]
  • Cheville JC, Lloyd RV, Sebo TJ, Cheng L, Erickson L, Bostwick DG, Lohse CM, Wollan P. Expression of p27kip1 in prostatic adenocarcinoma. Mod Pathol. 1998 Apr;11(4):324–328. [PubMed]
  • Newcomb EW, Sosnow M, Demopoulos RI, Zeleniuch-Jacquotte A, Sorich J, Speyer JL. Expression of the cell cycle inhibitor p27KIP1 is a new prognostic marker associated with survival in epithelial ovarian tumors. Am J Pathol. 1999 Jan;154(1):119–125. [PMC free article] [PubMed]
  • Flørenes VA, Maelandsmo GM, Kerbel RS, Slingerland JM, Nesland JM, Holm R. Protein expression of the cell-cycle inhibitor p27Kip1 in malignant melanoma: inverse correlation with disease-free survival. Am J Pathol. 1998 Jul;153(1):305–312. [PMC free article] [PubMed]
  • Mal A, Poon RY, Howe PH, Toyoshima H, Hunter T, Harter ML. Inactivation of p27Kip1 by the viral E1A oncoprotein in TGFbeta-treated cells. Nature. 1996 Mar 21;380(6571):262–265. [PubMed]
  • Dellas A, Schultheiss E, Leivas MR, Moch H, Torhorst J. Association of p27Kip1, cyclin E and c-myc expression with progression and prognosis in HPV-positive cervical neoplasms. Anticancer Res. 1998 Nov-Dec;18(6A):3991–3998. [PubMed]
  • Kawana H, Tamaru J, Tanaka T, Hirai A, Saito Y, Kitagawa M, Mikata A, Harigaya K, Kuriyama T. Role of p27Kip1 and cyclin-dependent kinase 2 in the proliferation of non-small cell lung cancer. Am J Pathol. 1998 Aug;153(2):505–513. [PMC free article] [PubMed]
  • Jordan RC, Bradley G, Slingerland J. Reduced levels of the cell-cycle inhibitor p27Kip1 in epithelial dysplasia and carcinoma of the oral cavity. Am J Pathol. 1998 Feb;152(2):585–590. [PMC free article] [PubMed]
  • Lloyd RV, Erickson LA, Jin L, Kulig E, Qian X, Cheville JC, Scheithauer BW. p27kip1: a multifunctional cyclin-dependent kinase inhibitor with prognostic significance in human cancers. Am J Pathol. 1999 Feb;154(2):313–323. [PMC free article] [PubMed]
  • Zehbe I, Rätsch A, Alunni-Fabbroni M, Burzlaff A, Bakos E, Dürst M, Wilander E, Tommasino M. Overriding of cyclin-dependent kinase inhibitors by high and low risk human papillomavirus types: evidence for an in vivo role in cervical lesions. Oncogene. 1999 Apr 1;18(13):2201–2211. [PubMed]
  • Singh SP, Lipman J, Goldman H, Ellis FH, Jr, Aizenman L, Cangi MG, Signoretti S, Chiaur DS, Pagano M, Loda M. Loss or altered subcellular localization of p27 in Barrett's associated adenocarcinoma. Cancer Res. 1998 Apr 15;58(8):1730–1735. [PubMed]
  • Clurman BE, Porter P. New insights into the tumor suppression function of P27(kip1) Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15158–15160. [PMC free article] [PubMed]
  • Hengst L, Reed SI. Translational control of p27Kip1 accumulation during the cell cycle. Science. 1996 Mar 29;271(5257):1861–1864. [PubMed]
  • Pagano M, Tam SW, Theodoras AM, Beer-Romero P, Del Sal G, Chau V, Yew PR, Draetta GF, Rolfe M. Role of the ubiquitin-proteasome pathway in regulating abundance of the cyclin-dependent kinase inhibitor p27. Science. 1995 Aug 4;269(5224):682–685. [PubMed]
  • Esposito V, Baldi A, De Luca A, Groger AM, Loda M, Giordano GG, Caputi M, Baldi F, Pagano M, Giordano A. Prognostic role of the cyclin-dependent kinase inhibitor p27 in non-small cell lung cancer. Cancer Res. 1997 Aug 15;57(16):3381–3385. [PubMed]
  • Qian X, Jin L, Kulig E, Lloyd RV. DNA methylation regulates p27kip1 expression in rodent pituitary cell lines. Am J Pathol. 1998 Nov;153(5):1475–1482. [PMC free article] [PubMed]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...