IMR Press / EJGO / Volume 27 / Issue 3 / pii/2006155

European Journal of Gynaecological Oncology (EJGO) is published by IMR Press from Volume 40 Issue 1 (2019). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with S.O.G.

Distinguished Expert Series

Down-regulation of E-cadherin is closely associated with progression of cervical intraepithelial neoplasia (CIN), but not with high-risk human papillomavirus (HPV) or disease outcome in cervical cancer

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1 Unita Citoistopatologia, Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, Istituto Superiore di Sanita (ISS), Rome, Italy
2 Department of Infectious, Parasitic and Immunomediated Diseases, ISS, Rome, Italy
3 Laboratory of Clinical Microbiology and Virology, University Hospital "Policlinico Tor Vergata", Rome, Italy
4 Dipertimento di Ginecologia e Ostetrica, Azienda Ospedaliera S. Orsola Malpighi, Bologna, Italy
5 U.C.O. Anatomia Patologica, Istopatologia e Citodiagnostica, Ospedale Maggiore, Trieste, Italy
6 Ginecologia e Ostetrica, TFO, Istitu­to Regina Elena, Rome, Italy
7 Department of Oral Pathology, Institute of Dentistry, University of Turku, Finland
8 Department of Oncology & Ra­diotherapy, Turku University Hospital, Turku, Finland
Eur. J. Gynaecol. Oncol. 2006, 27(3), 215–223;
Published: 10 June 2006

Objective: E-cadherin plays a pivotal role in maintenance of normal adhesion in epithelial cells but has also been shown to sup­press tumour invasion and participate in cell signalling. Known to be capable of reversing the invasive phenotype of high-risk human papillomavirus (HPV)-transformed keratinocytes, E-cadherin is down-regulated in CIN and cervical cancer (CC), but still incom­pletely studied as an intermediate endpoint marker in this disease. Material and Methods: As part of our HPV-PathogenISS study, a series of 150 CCs and 152 CIN lesions were examined using immunohistochemical (IHC) staining for E-cadherin, and tested for HPV using PCR with three primer sets (MY09/11, GP5+/GP6+, SPF). Follow-up data were available from all squamous cell carcinoma (SCC) patients, and 67 CIN lesions were monitored with serial PCR for HPV after cone treatment. Results: Expression of E-cadherin was reduced in parallel with the increasing grade of CIN, with major down-regulation upon transition to CIN3 and further to invasive cancer (OR 6.95; 95% CI 2.67-18.09) (p = 0.0001). Negative markedly reduced E-cad­herin expression was a 90.9% specific indicator of CIN, with 97.4% PPV, but suffered from low sensitivity (27.0%) and NPV (9.1 %). E-cadherin expression was completely unrelated to HR-HPV (p = 0.982), and did not predict clearance/persistence of HR-HPV after treatment of CIN. Similarly, E-cadherin expression was not a prognostic predictor of CC in univariate or multivariate analysis. Conclusions: Down-regulation of E-cadherin was closely associated with progressive CIN and cell proliferation. It is tempting to speculate that part of this cell proliferation is mediated through the canonic Wnt signalling pathway, after liberation of transcrip­tionally competent β-catenin from the E-cadherin/catenin complex, most notably orchestrated by E6 and E7 oncoproteins of HR­HPV. Such a liberation of β-catenin would abrogate the negative transcriptional control of E-cadherin on the Lef/TCF/β-catenin responsive genes. The exact role of HR-HPV oncoproteins E6 and E7 in this process remains to be seen in future studies.

Cell adhesion
Oncogenic human papillomavirus
Cervical cancer
Virus clearance
CIN treatment
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