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Extracellular regulated kinase-2 immunoreactivity increases in parallel with cervical intraepithelial neoplasia grade in cervical neoplasia
  2. A. C. LAZARIS,
  3. P. BOGRIS*,
  4. S. KOUNELI,
  5. A. NONNI,
  7. E. KOURI,
  8. M. TZAVARA*,
  10. H. KOUTSELINI and
  1. *5th Gynaecological Department, “Elena Venizelou” Maternity Hospital, Athens, Greece
  2. 1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
  3. Department of Pathology, “Elena Venizelou” Maternity Hospital, Athens, Greece
  1. Address correspondence and reprint requests to: Andreas C. Lazaris, MD, 1st Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Street, 11527 Athens, Greece. Email: alazaris{at}


The cell cycle control system includes cyclins, cyclin-dependent kinases (CDK), and their inhibitors (CDK1). Extracellular regulated kinase (ERK1/2) (p44 and p42 mitogen-activated protein kinases [MAPKs]) is a component of the MAPK pathway, which is associated with cyclin D1 and CDK. It is a critical signaling system for the induction of cell proliferation, differentiation, and cell survival. The aim of this study was to investigate the usefulness of ERK2 expression as a marker of biological aggressiveness complementary to cervical intraepithelial neoplasia (CIN) grade as well as to compare its expression in preinvasive lesions with that in invasive carcinoma. Paraffin-embedded sections of 146 CIN lesions (32 CIN I, 49 CIN II, and 43 CIN III) and 22 invasive cervical carcinomas (13 squamous and 9 adenocarcinomas) were used for the standard immunohistochemical procedure with the application of the ERK2 monoclonal antibody. ERK2 staining displayed a cytoplasmic and nuclear pattern. The staining intensity was gradually increased according to the severity of the dysplastic lesions; ERK2 immunoreactivity was significantly increased in high-grade dysplastic lesions (CIN II and CIN III) and invasive carcinomas by comparison to low-grade dysplastic lesions (CIN I) (P < 0.001). When high-grade lesions were separately assessed, the differences between each one of them and CIN I retained their statistical significance: CIN II versus CIN I (P < 0.001) and CIN III versus CIN I (P < 0.001). In conclusion, our study found a direct relationship between the increasing grade of the dysplastic cervical lesions and the intensity of ERK2 staining, thus implying a role of ERK2 as an early event in cervical carcinogenesis.

  • cervical intraepithelial neoplasia
  • ERK2
  • immunohistochemistry

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