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Vascular endothelial growth factor and prognosis of cervical carcinoma

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Abstract

Objective: To evaluate vascular endothelial growth factor (VEGF) as a marker for predicting lymph node metastasis and an independent prognostic factor of early-stage cervical carcinoma.

Methods: One hundred thirty-five women with stage IB–IIA cervical carcinoma had radical abdominal hysterectomies and pelvic lymph node dissections. Intratumoral cytosol VEGF concentrations were assayed with enzyme immunoassay. Histopathologic items and cytosol VEGF-influencing clinical outcomes were compared.

Results: Twenty-two women (16.3%) who had disease recurrence had higher levels of cytosol VEGF (1020 versus 112 pg/mg protein, P < .001) than those without recurrence. Using a cutoff value of 400 pg/mg protein resulted in best sensitivity of 75%, best specificity of 70%, positive predictive value of 41%, and negative predictive value of 92%. Only overexpressed cytosol VEGF (hazard ratio 6.44, P < .001) was an independent prognostic factor of disease-free survival. The overexpressed cytosol VEGF (hazard ratio 4.50, P = .021) and positive lymphovascular emboli (hazard ratio 4.11, P = .045) were independent prognostic factor of overall survival.

Conclusion: Cytosol VEGF might be a biomarker for the status of pelvic lymph nodes in early-stage cervical carcinoma and an independent prognostic indicator of its outcome.

Section snippets

Patients and methods

From January 1994 to June 1999, 135 subjects were enrolled with stage Ib-IIa cervical carcinoma who had radical abdominal hysterectomies and pelvic lymph node dissections. Women treated with conization, radiotherapy, or chemotherapy before surgery were excluded. The operation method used was the standard type III Wertheim hysterectomy, plus dissection of common iliac and pelvic lymph nodes en bloc. Clinicopathologic characteristics such as demographics, stage, tumor size, histologic type, depth

Results

Patients’ ages ranged from 29–71 years with a mean age of 50.6 years. Sixty-four (47.4%) were postmenopausal. One hundred twenty-two (90.4%) had stage IB and 13 (9.6%) had stage IIA cervical cancer. Pathologic examination showed 103 (76.3%) squamous cell carcinomas, 25 (18.5%) adenocarcinomas, five (3.7%) adenosquamous cell carcinomas, and two (1.5%) small cell carcinomas. Pelvic lymph node metastases were found in 28 of the 135 women (20.7%). Tumor size ranged from 0.3–6.0 cm (mean 2.6). Fifty

Discussion

Tumor angiogenesis is a complex process that involves endothelial cell proliferation, digestion of the extracellular matrix surrounding capillaries, endothelial cell migration, and differentiation into functioning capillaries. Evidence supports the concept that tumors can induce angiogenesis through many angiogenic molecules. VEGF is the most potent angiogenic molecule at present, not only inducing endothelial cell proliferation, but increasing vascular permeability. Our previous studies showed

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