VEGF-A is the most potent angiogenic factor in tumour angiogenesis. Its effects are mediated via two receptors VEGFR-1 and VEGFR-2. Primary aim of our study was to examine the expression of VEGFR-1 in breast cancer and its correlation to VEGF expression, lymph node status, tumour size, histological grade, and hormone receptor status. To examine the VEGFR-1 and VEGF expressions in tumour and surrounding tissue of 51 breast cancer patients, and in healthy breast tissue of 30 benign breast diseases patients, we used three-step immunohistochemical staining. VEGFR-1 and VEGF expressions were significantly increased in breast cancer tumour in relation to surrounding tissue (P < 0.01), and the VEGF expression was significantly increased in lymph node positive breast cancer patients (P < 0.01). VEGFR-1 and VEGF expressions were significantly higher in breast cancer tumour compared with healthy breast tissue (P < 0.01). Significant correlation between VEGF and VEGFR-1 expressions was found (P < 0.05). No significant correlations between VEGF and VEGFR-1 expressions and tumour size, histological grade, and hormone receptor status were found. Increased expression of VEGFR-1 and VEGF in breast cancer tumour and significant correlation between these proteins suggest the possible role of VEGF/VEGFR-1 signalization in breast cancer development, although VEGFR-1 potential prognostic value was not confirmed.

INTRODUCTION The aim of this study was to investigate the presence and the expression levels of the interleukin 13 (I1-13) in the primary breast cancer tumour tissue in relation to the unchanged breast tissue in the same patients and to the breast tissue in the patients with benign breast disease, and to investigate the correlation between the IL-13 expression levels and the pathohistological factors, and between IL-13 expression and estrogens and progesterone receptor status. MATERIALS AND METHODS 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in this prospective case-control study. The three-step immunohistochemical staining was used for testing the levels of IL-13 expression and hormone receptor status. RESULTS IL-13 was present in breast cancer tumour tissue, and in the surrounding unchanged tissue in the same patients, and in breast tissue in patients with benign breast disease. The expression of IL-13 was significantly higher in breast cancer tumour compared with surrounding tissue (P < 0.05) of the same, lymph node-positive patients. In addition, IL-13 expression was significantly higher in breast cancer tumour compared with breast tissue in patients with benign breast diseases (P < 0.01). There was significant correlation between IL-13 expression and tumour size in patients with lymph node-negative breast cancer (r = 0.405, P = 0.050). There was no significant correlation between IL-13 expression and the other pathohistological factors, and no significant correlation between IL-13 expression and the lymph node status. CONCLUSION Obtained results suggest possible involvement of IL-13 in breast carcinogenesis.

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL Objective. To date, there is no consensus on the optimal diagnostic and therapeutic strategy for patients with carcinoma of unknown primary (CUP) of the neck. These tumors are heterogeneous in their clinical and biological characteristics, and a pre-operative prognostic marker is desirable to optimize therapy and improve outcome and survival. Human papillomavirus (HPV) is an etiologic factor in a subgroup of head and neck squamous cell carcinomas and has been identified as a significant prognostic biomarker. We sought to determine if HPV also may add relevant information on the origin and prognosis of these tumors. Material and method. 47 patients (mean age 58.7 years; 40 men, 7 women) presenting with CUP of the neck between 1994 and 2008 in Cologne were examined by standard diagnostic procedures including radiological imaging of the head, neck, thorax and abdomen, positron emission tomography (PET), panendoscopy, curettage of the nasopharynx, bilateral tonsillectomy and blind probes of the base of tongue. All patients were surgically treated with neck dissection of the diseased neck as well as adjuvant chemoradiation. The mean follow up time was 34 months. Formaldehyde-fixed, paraffin-embedded tissue specimens of the 47 metastases were examined retrospectively by means of p16INK4A immunohistochemistry, HPV-specific PCR and fluorescence in situ hybridization. Results were correlated with clinical follow-up data. Results. Oncogenic HPV was present in 12/47 (26%) metastases (10 with HPV 16), which showed also p16INK4A overexpression. In 42% of CUP patients the primary tumor was discovered during follow-up. A significant correlation between HPV positivity and later detection of the primary tumor in the oropharynx was found (p=0.038). Moreover, patients with a p16INK4A- (13/47) or HPV-positive tumor had a more favorable overall 5-year survival rate then p16INK4A- and HPV-negative tumors (69% vs 33%, p=0.05; 65% vs 37%, p=0.093; respectively). Conclusion. HPV is present in a quarter of neck metastases of CUP patients and the presence of oncogenic HPV and p16INK4A expression can serve to locate the primary tumor in the oropharynx. In addition, both biomarkers are indicators of a favorable prognosis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2255. doi:10.1158/1538-7445.AM2011-2255

AIM To investigate the presence and expression levels of the IL-18 in the primary breast cancer tissue in relation to the unchanged breast tissue in same patients and the breast tissue in patients with benign breast disease, as well as the correlation between the IL-18 expression levels and pathohistological factors, including the correlation between IL-18 expression and the estrogens and progesterone receptor status. METHODS This prospective randomized study was conducted at the Policlinic for Laboratory Diagnostics of the University Clinical Centre of Tuzla. 50 patients with invasive ductal breast cancer and 20 patients with benign breast diseases were included in the study. The tree-step immunohistochemical staining was used for testing the levels of IL-18 expression and hormone receptor status. RESULTS IL-18 was present in the breast cancer tumour, in the surrounding unchanged tissue of the same patients and in the breast tissue of patients with benign breast tumour and other benign breast disease. The expression of this interleukin was significantly higher in breast cancer tumour tissue as compared to its expression in surrounding unchanged tissue of the same patients (p < 0.05), whereas IL-18 expression was not significantly higher in breast cancer tumours compared to its expression in breast tissue of the patients with benign breast diseases (p = 0.057). There was no significant correlation between IL-18 expression and the lymph node status, and between IL-18 expression and the pathohistological factors. CONCLUSION The results suggest possible involvement of IL-18 in complex mechanisms of breast carcinogenesis.

The study was designed to determine pre-, intra-and postoperative serum cortisol and prolactin (PRL) concentrations in patients subjected to low abdominal surgery under total intravenous anesthesia (TIVA) with propofol-fentanyl, and under general balanced anesthesia with isoflurane-fentanyl. The prospective study included 50 patients of both sexes, aged between 35 and 60 years, subjected to elective low abdominal surgery. Patients were randomly divided into two groups: an experimental group, consisting of 25 ASA I/II (American Society of Anesthesiologists I/II classification) patients treated under TIVA with propofol-fentanyl, and a control group consisting of 25 ASA I/II patients treated under balanced anesthesia with isoflurane-fentanyl. The length of the surgery and the degree of the surgical trauma did not differ significantly between the two anesthesia groups. Blood samples for cortisol and PRL measurements were drawn at exact time points: 30 minutes before the beginning of the surgery (T0), 30 minutes after the beginning of the surgery (T1), at the end of the surgery (T2), 2 hours after the surgery (T3), and 24 hours after the surgery (T4). Serum levels of cortisol and PRL were measured using commercially available kits. The results were evaluated with the nonparametric Mann-Whitney test. The serum concentration of cortisol measured at T1 time point in patients treated under TIVA was significantly lower (p=0.04) than that in patients treated under general balanced anesthesia. The average circulating levels of PRL measured at T1, T2 and T3 time points in patients treated under TIVA were significantly lower (p=0.003; p=0.002; p<0.05; respectively) than those in patients treated under balanced anesthesia. The results obtained suggest that the endocrine stress response developed in response to surgery is probably attenuated in patients treated under TIVA with propofol-fentanyl and, thus, that these patients are less stressed in comparison to patients treated under general balanced anesthesia with isoflurane-fentanyl.

OBJECTIVES In order to assess diagnostic value of prolactin (PRL) in breast cancer (BC), we examined its serum levels and frequencies of its increase in breast cancer patients (BCP), and compared them to those in two controls. We also determined circulating levels of PRL in localised and advanced BC and calculated sensitivity and specificity of PRL in BC. PATIENTS AND METHODS The main experimental group consisted of 47 female patients with histologically confirmed diagnosis of BC. The obtained results were compared to those in two control groups: clinically healthy women, and female patients with other types and locations of cancer. Serum levels of PRL were measured by means of radioimmunoassay. Results were processed by means of t-test and two way analysis of variance. RESULTS The serum levels of PRL before treatment, as well as the frequencies of its increase, were significantly higher in BCP in comparison to controls (p<0.01, 0.02). The average circulating levels of PRL in patients with advanced BC were significantly higher (p<0.0001) in comparison to patients with localised disease. Sensitivity for PRL in BC was 50%, and specificity was 100%. CONCLUSIONS Increased levels of PRL can be detected in the majority of patients with advanced BC. PRL has high specificity for BC, especially for metastatic BC, which leads to its diagnostic and prognostic importance in this disease.

AIM To correlate prolactin concentrations in the sera of patients with metastatic breast cancer with time interval to appearance of metastases, their location, and size. METHOD The prospective study included 46 female patients with histologically confirmed diagnosis of breast cancer. The patients were recruited from the Health Center outpatient clinic and University Hospital Center day-care hospital in Banja Luka, Bosnia and Herzegovina, from January to August 1988. The follow up lasted 5 years. Serum concentrations of prolactin were measured in all patients before (baseline levels) and after the therapy at regular time intervals during the observation period. Their prolactin concentrations were compared with prolactin concentrations in 40 healthy women and 33 female patients with other types of cancer, who served as control groups. Time interval to metastases development, their size, and location were determined in breast cancer patients and compared with those in patients with other types of cancer. RESULTS The baseline serum concentrations of prolactin were higher in breast cancer patients than in healthy women (610 vs 442 mU/L; p=0.04; Mann-Whitney test), and in patients with other locations of cancers (662 vs 481 mU/L, respectively; p=0.02; Mann Whitney test). Metastases developed in all hyperprolactinemic patients, whereas a third of normoprolactinemic were free of metastases. The average time interval before the occurrence of metastases in patients with very high serum concentrations of prolactin was significantly shorter than that in patients with very low prolactin concentrations (54.3 vs 6.1 months; p<0.001; Mann Whitney test). In hyperprolactinemic patients with metastatic breast cancer, there was a significant correlation between the serum concentration of prolactin before treatment and the time to metastases (r= -0,47; p=0.03) and the size of metastases (r=0,64; p=0.001). CONCLUSION Hyperprolactinemia could be an indicator of disease progression and poor prognosis in patients with metastatic breast cancer.