Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy

Vol. 52 No. 1 Suppl., 2011
This supplement was not sponsored by Outside Organizations.

ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Viorica Magdalena Nagy, R. Buiga, Ioana Brie, N. Todor, Oana Tudoran, Claudia Ordeanu, Piroska Virag, Oana Tarta, Meda Rus, O. Balacescu

Introduction: Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. Materials and Methods: So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. Results: Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients' age (p=0.06). From the large panel of studied markers it was observed correlation between MVD expression with stromal COX-2 (p=0.01) and a tendency with epithelial COX-2 (p=0.06). Stromal COX-2 has higher correlation with VEGFR2 (p=0.01) and MVD (p=0.01) and also has a lower correlation with tumor size (p=0.08). Conclusions: Univariate analysis demonstrates that the response to radio-chemotherapy in cervical cancer is related to a set of clinical and molecular factors as: the tumor size, the expression of VEGFR2 as mRNA level and the patients' age. Unfortunately, the multivariate analysis by logistic model selects only VEGFR2 expression for prediction of tumor response. The interrelations between the different biomarkers demonstrate the complexity of the tumor progression process and the necessity of further studies to identify new therapeutic targets.

Corresponding author: Viorica Magdalena Nagy, Professor, MD, PhD, e-mail: nagyviorica@yahoo.com

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ROMANIAN JOURNAL of MORPHOLOGY and EMBRYOLOGY

Carmen Corina Stancu, I. E. Plesea, S. D. Enache, R. Diaconescu, A. Camenita, Mihaela Tenovici

Aim. The study is an integrated assessment of clinical, imagistic and morphological parameters in severe intracerebral hemorrhages (ICH) complicated with subarachnoid effusion (SAE). Materials and Methods. The studied group had 37 cases of patients with ICH and SAE who were hospitalized in the Emergency County Hospital of Craiova and died during hospitalization. The parameters evaluated were clinical (relation with the seasons, age, sex, arterial blood pressure, the motor deficit, degree of coma and Glasgow score at admission) and morphological (the sites of the intraparenchymal hematoma and SAE, the size of the intraparenchymal hematoma, the presence of the mass effect, and the association of intraventricular effusion). The latter were assessed on CT films and during autopsy. Results. The presence of SAE as a complication of ICH showed a predilection for cold seasons, especially winter. From the 37 studied cases, 18 were men and 19 women. 51.3% of the patients were in the fourth and fifth life decade. Almost 73% of the patients had third stage arterial hypertension at admission, over 56% motor deficits and almost 49% Glasgow scores lower than 6. The hematomas had huge dimensions as compared to hosting encephalic structures, in lobar sites involving more than one lobe. Other risk factors as mass effect, perilesional edema and intraventricular extension (IVE) were constantly present. Conclusions. The association of SAE with other independent risk factors such as hypertension, low Glasgow scores, dimensions of hemorrhagic foci, presence of mass effect, perilesional edema and intraventricular extension (IVE) results in the death of patient despite any sustained therapeutical intervention.

Corresponding author: Carmen Corina Stancu, PhD, e-mail: doctorstancu@yahoo.com

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