The epidermal growth factor receptor pathway in relation to pelvic lymph node metastasis and survival in early-stage cervical cancer

• Published in: Human pathology 2010-12, Vol.41 (12), p.1735-1741
• Main Authors: Eijsink, Jasper J.H., MD, Noordhuis, Maartje G, ten Hoor, Klaske A, Kok, Mirjam, Hollema, Harry, MD, PhD, de Bock, Geertruida H., PhD, Nijman, Hans W., MD, PhD, Schuuring, Ed, PhD, Wisman, G. Bea A., PhD, van der Zee, Ate G.J., MD, PhD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomarkers, Tumor - metabolism; Cancer therapies; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - secondary; Cervical cancer; Cervix Uteri - metabolism; Cervix Uteri - pathology; Cervix Uteri - surgery; Chemotherapy; EGFR pathway; Epidermal growth factor; Extracellular Signal-Regulated MAP Kinases - metabolism; Female; Female genital diseases; Genes; Gynecology. Andrology. Obstetrics; Hematologic and hematopoietic diseases; Humans; Investigative techniques, diagnostic techniques (general aspects); Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph Nodes - pathology; Lymphatic Metastasis; Medical sciences; Metastasis; Middle Aged; Mutation; Netherlands - epidemiology; Odds Ratio; Pathology; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Pelvis; Phosphorylation; Prognosis; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - metabolism; Radiation therapy; Receptor, Epidermal Growth Factor - metabolism; Review boards; Studies; Surgery; Survival; Survival Rate; Tissue Array Analysis; Tumors; Uterine Cervical Neoplasms - metabolism; Uterine Cervical Neoplasms - mortality; Uterine Cervical Neoplasms - pathology; Young Adult
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2010.04.017

Summary 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.