Radioligand binding assay determination of epidermal growth factor receptor in ovarian tumours.

PURPOSE: To introduce a quantitative method for determination of epidermal growth factor receptor (EGFR) expression in tissue samples taken from normal ovaries, benign and malignant ovarian tumours, convenient for routine tests. MATERIALS AND METHODS: About 1g of tissue was taken intraoperatively from 136 patients; 105 of them had histologically verified ovarian tumours (64 malignant, 42 benign) and 30 had normal ovaries. The tissue was frozen, preserved and transported in liquid nitrogen (-196 degrees C). The level and frequency of EGFR expression were determined by radioligand method, utilizing (125)I-labeled epidermal growth factor (EGF) and recombinant human EGF. The results were obtained as fmol bound EGF per mg protein from the membrane fraction. All samples having expression >/=3 fmol/mg were considered as positive. RESULTS: The frequency of EGFR expression was 52% (70/136 patients), with a mean level of expression 45 +/-11 fmol/mg (range 0-1332). From the EGFR-positive patients with malignant ovarian tumours 21 (62%) had progressive disease (PD) while only 4 (13%) patients with negative EGFR had PD (p=0.001). The mean progression-free interval in the first group was 4 months, and in the second group it was 11 months (p=0.0028). CONCLUSION: The proposed quanitative radioligand binding assay is easy to perform, rapid and well reproducible, and we recommend it for routine clinical use.

Familial breast cancer. Part IV: survival of familial breast cancer in Bulgarian patients.

PURPOSE: The aim of part IV of this study was to register and compare the survival rates of sporadic and familial breast cancer, and to estimate the prognostic value of familial predisposition of the disease as a risk factor. PATIENTS AND METHODS: We investigated retrospectively 504 patients belonging to families with accumulation of the disease (study group, group I) and 300 patients with the sporadic form of breast cancer (control group, group II). All patients were diagnosed, treated, and followed-up at the Clinic of Thoracic Surgery, National Oncological Centre. For determination of the familial predisposition we used the Anderson's classification. The statistical significance of the difference between two groups and subgroups was evaluated by the x(2) Pearson's test and Student's paired t-test. RESULTS: Women with familial breast cancer were characterized by worse survival rates compared to the sporadic cases. Of the patients in group I 20.79% survived more than 5 years versus 76.74% in group II (p <0.0000). Group I patients with first degree of kinship had the lowest survival rates. Highly significant differences were found in survival, depending on stage: in group I stage IIA patients the survival was 42.86% versus 97.73% for group II; in IIB it was 14.17% versus 89.41%; and in IIIA it was 4.76% versus 75.00%, respectively. Tumor size, lymph nodes status, metastases and steroid receptors also showed a high statistical difference in survival between the 2 groups. Five-year survival in group I patients without metastases was 22.34%, while it was 80.71% in group II. In patients with metastases 4-year survival rates were 2.94% and 22.22%, respectively. Estrogen receptor (ER)-negative patients in groups I and II had 5-year survival of 17.41% and 72.06%, respectively. Progesterone receptor (PR)-negative patients in groups I and II had 5-year survival of 17.50% and 83.67%, respectively. Invasive lobular and invasive ductal carcinoma showed very poor survival in both groups (18.75% and 17.73% in group I versus 53.33% and 77.48% in group II, respectively). CONCLUSION: Familial breast cancer displays particular clinical characteristics that differ from the sporadic form of the disease in terms of clinical, histological and biochemical features. Our results show that patients with familial breast cancer have significantly lower survival rates in comparison with women with the sporadic form of the disease. The need for surveillance and diagnosis of the disease at an earlier stage is crucial for women with familial predisposition for breast cancer.

Familial breast cancer. Part II: Relationships with histology, staging, steroid receptors and serum tumor markers.

PURPOSE: To identify differences in clinical characteristics, histological features, hormone receptor status, and tumor marker expression between patients with sporadic and familial breast cancer. PATIENTS AND METHODS: As in the previous Part I of this study, two groups of women with breast cancer were compared. The first group (group I) included 504 patients with a family history of breast cancer. The second (control) group (group II) consisted of 300 patients not reporting such a history in their relatives. The examined parameters in this report were stage and axillary lymph node involvement at the time of the initial diagnosis, treatment methods, hormone receptor status, and serum levels of the tumor markers CEA and CA 15.3. The data were processed and analysed using the SPSS statistical package. The statistical significance of differences between groups and subgroups was evaluated by x(2) Pearson's test and Student's paired t-test. RESULTS: Compared to sporadic cases, patients with familial breast cancer were more often diagnosed at an advanced III or IV stage; metastatic involvement of the regional lymph nodes was more frequent in group I patients. In the same group more radical surgical procedures combined with chemotherapy and local irradiation were performed. In group I the percentage of negative hormone receptors was higher (35.3% versus 22.6%; p <0.0001) for estrogen receptors (ER), and 47.6% versus 32.6% (p <0.0001) for progesterone receptors (PR). Also, in group I raised serum levels of CA 15.3 were significantly more frequent compared with group II (48% versus 35.5%, p <0.0789), and this applied also for CEA values above 50 ng/ml (10.6% versus 1.5%, p <0.0002). CONCLUSION: Familial breast cancer displays particular clinical characteristics, distinguishing it from the sporadic type of the disease. Patients with familial breast cancer are usually diagnosed at an advanced stage. Commonly, the hormone receptors are negative and the serum concentrations of tumor markers elevated. The steroid receptor status represents the most reliable predictor of response to hormonotherapy and an important prognostic factor of the patient's outcome. As a result of their particular characteristics, these patients require more radical surgical techniques combined with pre- or postoperative local radiotherapy and systemic chemotherapy.

Familial breast cancer. Part III: Genome instability and cancer risk.

PURPOSE: The purpose of part III of this study was to direct our efforts towards more detailed genetic studies, which can be used in genetic counselling of patients with breast cancer and their relatives. PATIENTS AND METHODS: We investigated 52 patients, 25 with chromosomal fragility and 17 with spontaneous chromosomal aberrations, all with familial breast cancer (study group). The control group consisted of 10 healthy women without a history of proliferative diseases or breast cancer in their families. The chromosomal fragility and spontaneous chromosomal aberrations were studied in peripheral blood lymphocytes cultured for 72 and 48 hours, respectively, at 37 degrees C, following a standard procedure. RESULTS: In the patients with breast cancer the expression of chromosomal fragility was significantly higher (19.47%) compared to 11.61% in the control group (p<0.0001). In the patients with familial breast cancer the spontaneous chromosomal aberrations were significantly higher (6.72%) compared with those of the normal individuals (1.98%, p<0.0001). In the study group spontaneous breaks in a single lymphocyte were 0.15, while they were 0.05 in the control group (p<0.0001). CONCLUSION: The values of chromosomal fragility and chromosomal aberrations have some practical and theoretical importance in genetic services. The different variants in genomic stability are related with individual breast cancer development risk. Our results support the idea that the fragile sites and chromosomal aberrations may act as predisposing factors in carcinogenesis.

Effect of short-term losartan treatment in patients with primary aldosteronism and essential hypertension.

The aim of this study was to investigate the effect of short-term treatment with losartan, a selective and competitive angiotensin II (AngII) receptor blocker, on vascular endothelial growth factor (VEGF), active renin and kallikrein activity (KA) in patients with essential hypertension and primary aldosteronism. Nine patients with primary aldosteronism (5 with Conn adenoma and 4 with idiopathic hyperaldosteronism) and 9 patients with essential hypertension were included in the study. Systolic and diastolic blood pressure decreased significantly after losartan treatment in both patient groups. Plasma and urinary Kallikrein activity were significantly higher in primary aldosteronism in comparison with essential hypertension. There were no significant changes in the active renin and aldosterone in patients with primary aldosteronism after treatment. Plasma and urinary KA decreased significantly after losartan administration in both groups. Serum VEGF levels in primary aldosteronism were not significantly different from those in essential hypertension and did not change significantly after treatment in either group. In conclusion, losartan, in usual therapeutic doses, lowers blood pressure in patients with primary aldosteronism and essential hypertension. This marked antihypertensive effect in primary aldosteronism could be explained predominantly by blockade of tissue renin-angiotensin system (RAS). The variations in KA could be due to hemodynamic changes. VEGF is not likely to be involved in the action of losartan.

Trandolapril in Cushing's disease: short-term trandolapril treatment in patients with Cushing's disease and essential hypertension.

A study was performed on seven patients with Cushing's disease and seven age and sex matched patients with essential hypertension. The patients maintained their usual diet and sodium intake and received the ACE inhibitor trandolapril at a dose of 2 mg daily for 8 days. Trandolapril treatment resulted in an increase in the active renin and decrease in the urinary kallikrein activity in both study groups. Blood pressure decreased significantly in patients with Cushing's disease and essential hypertension after 8 days of trandolapril treatment. The opposite responses of renin and kallikrein to ACE inhibition support a possible feed-back mechanism of regulation between the renin-angiotensin system and the kallikrein-kinin system.

Losartan in Cushing's syndrome.

Eleven patients with Cushing's syndrome were included in the study. They maintained their usual sodium intake and received a single oral dose of 50 mg of the angiotensin II antagonist receptor losartan for 3 days. Losartan treatment resulted in stimulation of active renin and decrease of plasma and urinary kallikrein activity. Both systolic and diastolic blood pressure decreased independently of baseline level of active renin. The relationship between kallikrein and renin-angiotensin system are discussed.

Role of radioimmunoscintigraphy and SPET in the diagnosis of patients with malignant melanoma.

The aim of the study was to compare the effectiveness of radioimmunoscintigraphy and single photon emission tomography in the diagnosis of malignant melanoma. Radioimmunoscintigraphy was carried out on 47 patients with stage I to IV malignant melanoma. Seven patients had primary melanoma; the remaining patients had 57 clinically suspected lesions. 99Tcm-F(ab)2 was injected intravenously or subcutaneously. Imaging was site and size dependent with the highest sensitivity in the lymph nodes (96%). Sensitivity was lowest in cutaneous and subcutaneous lesions using planar scintigraphy (20.5%) although it was higher using single photon emission tomography (42.8%). It is concluded that the advantages of radioimmunoscintigraphy over other methods of investigation are its specificity and selectivity. It therefore has potential as a diagnostic tool concerning the status of melanoma patients.

Radioimmunoassay of alpha-fetoprotein in the serum of patients with leukemia and malignant melanoma.

A sensitive double antibody radioimmunoassay has been used to measure Alpha-fetoprotein in the serum of healthy subjects, pregnant women and patients with a variety of malignant diseases including leukemia and melanoma. Elevated serum Alpha-fetoprotein levels were found in 2 of 35 patients with leukemia, 2 of 10 with melanoma. All the pregnant women studied had raised levels.

Alpha-fetoprotein in the serum of patients with neoplasms of the gastrointestinal tract.

Serum alpha-fetoprotein was estimated in 61 patients with neoplasms of the gastrointestinal tract, 29 healthy controls and 10 pregnant women. Almost half ot the patients had increased values of alpha-fetoprotein and no parellelism between alpha-fetoprotein and liver metastasis was found. Decreasing of the alpha-fetoprotein during the postoperative period could be considered a sign for a total removal of the tumor, and, on the contrary -- increasing of alpha-fetoprotein -- for a recurrence.