title: The epidermal growth factor receptor pathway in relation to pelvic lymph node metastasis and survival in early-stage cervical cancer.
abstract: The objective of this study is to correlate the expression of epidermal growth factor receptor (EGFR) components with clinical behavior of early-stage cervical cancer. Tissue samples of 336 consecutive Federation of International Gynecologists and Obstetricians stage IB-IIA cervical cancer patients all treated primarily by radical surgery were collected. Clinicopathologic and follow-up data were prospectively obtained during standard treatment and follow-up. As representatives for the EGFR pathway, expression of EGFR, pEGFR, PTEN, pAKT, and pERK was assessed by immunohistochemistry on tissue microarrays. Positive immunostaining was observed for EGFR in 32.1%, for pEGFR in 21.0%, for PTEN in 38.3%, for pAKT in 5.3%, and for pERK in 4.3% of tumor samples. Positive EGFR immunostaining was associated with squamous cell carcinoma of the cervix (odds ratio [OR], 7.41; 95% confidence interval [CI], 3.38-16.23, P < .001), negative pEGFR immunostaining with poor differentiation (OR, 0.39; 95% CI, 0.20-0.73, P = .004), and negative PTEN immunostaining with metastatic pelvic lymph nodes (OR, 0.51; 95% CI, 0.30-0.90, P = .019). In multivariate analysis, only pelvic lymph node metastasis (hazard ratio, 6.11; 95% CI, 3.46-10.77, P < .001) and poor differentiation (hazard ratio, 1.91; 95% CI, 1.12-3.26, P = .018) were related to disease-specific survival. In early-stage cervical cancer, loss of PTEN expression is associated with pelvic lymph node metastasis, suggesting PTEN to be one of the tumor suppressor genes affecting pelvic lymph node metastasis. However, expression of EGFR pathway components does not appear to have prognostic impact in surgically treated early-stage cervical cancer.
authors.affiliation: Department of Gynaecologic Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jasper J H
authors.initials: JJ
authors.lastname: Eijsink
authors.forename: Maartje G
authors.initials: MG
authors.lastname: Noordhuis
authors.forename: Klaske A
authors.initials: KA
authors.lastname: ten Hoor
authors.forename: Mirjam
authors.initials: M
authors.lastname: Kok
authors.forename: Harry
authors.initials: H
authors.lastname: Hollema
authors.forename: Geertruida H
authors.initials: GH
authors.lastname: de Bock
authors.forename: Hans W
authors.initials: HW
authors.lastname: Nijman
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: G Bea A
authors.initials: GB
authors.lastname: Wisman
authors.forename: Ate G J
authors.initials: AG
authors.lastname: van der Zee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D010388:Pelvis; D010766:Phosphorylation; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015996:Survival Rate; D046888:Tissue Array Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human