Extracellular regulated kinase-2 immunoreactivity increases in parallel with cervical intraepithelial neoplasia grade in cervical neoplasia.
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.
Kapetanios
V
V
5th Gynaecological Department, "Elena Venizelou" Maternity Hospital, Athens, Greece.
Lazaris
A C
AC
Bogris
P
P
Kouneli
S
S
Nonni
A
A
Arvaniti
H
H
Kouri
E
E
Tzavara
M
M
Giannakodimos
G
G
Koutselini
H
H
Patsouris
E S
ES
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D016001:Confidence Intervals; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D016017:Odds Ratio; D011336:Probability; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000235:genetics / Q000276:immunology / Q000473:pathology*
D014408:Biomarkers, Tumor; D019950:Mitogen-Activated Protein Kinase 1