Aim: To perform a comparative analysis with simultaneous measurement of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF1) and matrix metalloproteinase 7 (MMP7) in serum samples taken from healthy women and ovarian cancer patients; to perform association of these markers with their expression in primary tumors depending on clinical, morphological and biochemical characteristics of the disease and its prognosis. Materials and methods: We assessed 54 treatment-naïve patients with ovarian cancer aged from 23 to 74 years (mean ± SD, 53.2 ± 1.9), being at various FIGO stages of the disease. The control group consisted of 120 healthy women of matched age and reproductive status, in whom serum biomarker levels were studied. Patient survival was assessed by the Kaplan-Meier method, with survival curves compared with log-rank test. All analyses were done with “STATISTICA” and SPSS software. Results: Serum VEGF levels in ovarian cancer patients were significantly (p < 0.0001) higher compared those in the control. The most informative cut-off values differentiating the groups studied were serum VEGF values of < 350 pg/ml (median value in the control) and > 505 pg/ml (upper quartile in the control). With 505 pg/ml taken as a threshold, the test had sensitivity of 79.6% and specificity of 75%. Another cut-off value of serum VEGF level between the patients with ovarian cancer and the control group (510 pg/ml) was derived from ROC curves and 75% sensitivity and 78.2% specificity. No acceptable cut-off value for serum IGF1 to differentiate between the patients with ovarian cancer and the controls could be obtained from the ROC curves. Serum MMP7 levels in the patients with ovarian cancer were significantly higher than those in the control group (Mann-Whitney test p < 0.0001). With ROC curves, the best sensitivity to specificity ratio for MMP7 value of 4.6 ng/ml was obtained to differentiate between the patients with ovarian cancer and the controls (sensitivity 83.3%, and specificity 81%). The variance analysis did not reveal any association between serum VEGF, IGF1 and MMP7 and age of patients with ovarian cancer, tumor histology, concomitant somatic and gynecological diseases, and CA-125 levels. Serum VEGF and IGF1 levels did not correlate with the stage of ovarian cancer, in contrast to MMP7, whose levels were significantly higher in stages IIIc–IV. The median VEGF level significantly increased as the degree of differentiation decreased from 510 to 622 pg/ml (p < 0.002), while median IGF1, on the contrary, decreased from 219 to 116 pg/ml (p < 0.0001). There was a direct correlation between serum and tumor VEGF levels in ovarian cancer patients (r = 0.65, p < 0.0001). On the contrary, there was an inverse correlation between serum and tumor IGF1 levels (r = -0.68, p < 0.0001). Serum and tumor MMP7 levels remained unrelated to each other. Tumor VEGF, IGF1 and MMP7 content was unrelated to the age of the patients, their reproductive status, presence of concomitant somatic and gynecological diseases, histology of ovarian cancer, and serum CA-125 levels. VEGF levels in the tumor were not associated with the stage of ovarian cancer, but in patients with initial stages Ia and Ib stages MMP7 values significantly lower (2.1 ng/mg protein) compared to those in stages IIIc and IV (6.1 and 4.7 ng/mg protein, respectively, p < 0.05). Similar pattern was noted for IGF1: tumor IGF1 values in the patients with stages Ia–Ib were significantly lower (0.5 ng/mg protein) than those with stages IIIc–IV (median, 1.3–1.4 ng/mg protein). A significant increase in both serum and tumor VEGF levels was detected in the patients with ovarian cancer with decreased degree of differentiation. On the contrary, tumor IGF1 levels, but not serum ones, were significantly increased from 0.6 to 1.4 ng/ml in the patients with poorly differentiated ovarian cancer. MMP7 tumor expression did not depend on the degree of its differentiation. Serum VEGF levels above 700 pg/ml and tumor levels of above 590 ng/mg protein should be considered as unfavorable prognostic factors in patients with ovarian cancer.

Insulin-like growth factors (IGF) 1 and 2 and IGF binding proteins (IGFBP) 1 and 3 levels were measured by ELISA techniques in blood serum of 74 primary colorectal cancer (СRC) patients and 30 control practically healthy persons. Significant increase of IGF-1 level and decrease of IGFBP-3 level were demonstrated in patients’ serum as compared to control group. Sensitivity of IGF-1 as a prospective diagnostic СRС marker comprised 80 % with 75 % specificity using 140 ng/ml as cut-off level. Significant negative association was found be-tween both patients and donors’ age and serum IGF-1 levels, but in CRC patients it was much weaker than in control group. No associations were found between serum IGF 1 and 2 levels and main criteria of colorectal cancer progression.

Serum levels of insulin-like growth factors (IGF-1 and IGF-2), IGF-binding proteins (IGFBP-1, IGFBP-2, and IGFBP-3) and vascular endothelial growth factor (VEGF) were measured by standard ELISA technique in 95 primary colorectal cancer patients and 48 healthy individuals. Significant increase in serum levels of IGF-1, IGFBP-2, and VEGF and decrease in IGFBP-3 level were demonstrated in patients in comparison with the control group; in male patients, serum level of IGF-2 was also increased. Sensitivity of IGF-1 as the prospective diagnostic marker of colorectal cancer was 80% and specificity was 75% at the threshold level of 140 ng/ml. Serum levels of IGF-1 significantly decreased with age in both patients and healthy donors, but in patients, this correlation was much weaker. These parameters did not correlate with the main clinical and morphological indices, such as dissemination, localization, and histological structure of colorectal cancer.

Enzyme immunoassay showed that the content of matrix metalloproteinases (MMP) 2 and 7 in tumors was higher than in the adjacent histologically intact tissue in 91 and 76% patients with breast cancer, respectively, while MMP-9 levels in the tumor and intact tissue were virtually the same. Serum concentrations of MMP-2 and MMP-7 did not correlate with their levels in the tumors, were within the normal range, and virtually did not decrease after removal of the primary tumor. Serum levels of MMP-9 in patients were significantly lower than in the control and increased after surgery in 85% patients. No clear-cut relationship between the studied parameters and clinical morphological prognostic factors of breast cancer was detected.

The expression of MMP-1, -2, -9 and TIMP-1 was studied in 10 benign cartilage-forming osteal tumors (5 osteochondromas and 5 chondromas) and 39 chondrosarcomas (14 central, 4 periosteal, 7 dedifferentiated, and 14 secondary tumors). No expression of MMP and TIMP-1 was detected in benign cartilage-forming osteal tumors. In chondrosarcomas, the expression of MMP-1 was detected in 84.6%, of MMP-2 in 71.8, of MMP-9 in 97.4, and of TIMP-1 in 82.4% cases, the levels of expression of these markers varied from 10 to 60%. The expression of MMP-1 was not associated with patient gender, maximum size and degree of differentiation of the tumor, but was linked with age. The expression of MMP-1 was more often detected in central and dedifferentiated chondrosarcomas; the expression of MMP-1(+) was significantly associated with 3-year relapse-free and 5-year overall survival of the patients. The expression of MMP-1 in the tumor was associated with unfavorable course of the disease. The values of MMP-2 expression in chondrosarcomas did not reflect the main clinical morphological characteristics of the disease and its prognosis. The level of MMP-9 protein expression in chondrosarcomas ≥40% is prognostically unfavorable, while <40% is a favorable factor for 3-year relapse-free survival. The risk of disease relapse within 1 year after the beginning of therapy was maximum in T3 tumors with expression of MMP-9 protein ≥40%. No relationships between the parameters of TIMP-1 expression in chondrosarcomas and the main clinical morphological characteristics of the disease and its prognosis were detected.

Here we present the results of comparative immunoenzyme assay of the initial serum levels of VEGF in breast cancer patients (stages T 1N 0M 0 and T 2N 0M 0) and apparently healthy women (controls). It was found that VEGF concentrations in the serum of patients with breast cancer stages T 1N 0M 0 and T 2N 0M 0 significantly surpassed the control levels. Increased levels of VEGF surpassing the threshold values were more often observed in patients with T 2N 0M 0 breast cancer compared to patients with T 1N 0M 0 tumor. Serum concentration of VEGF in patients with stages T 1N 0M 0 and T 2N 0M 0 breast cancer did not depend on patient’s age and reproductive function and receptor status of the primary tumor (estrogen and progesterone receptors), but was closely associated with tumor histogenesis and differentiation degree. Significantly higher levels of VEGF were observed in patients with lobular infiltrative breast carcinoma compared to patients with ductal tumors and in patients with low-differentiated tumors compared to highly and moderately differentiated tumors. High initial concentrations of VEGF (≥300 pg/ml) were more often detected in patients with T 2N 0M 0 breast cancer developing relapses within the fi rst 3 years of follow-up compared to patients without relapses during the corresponding period (p=0.001). These findings suggest that serum level of VEGF in patients with T 2N 0M 0 breast cancer before treatment can be used as an additional marker in parallel with standard clinical and morphological signs of the disease for more precise prognosis of early relapse.

A significant increase of matrix metalloproteinases’ (MMP) 2 and 7 levels in the tumors as compared to adjacent histologically unchanged mammary gland was demonstrated by enzyme-linked immunosorbent assays in 91 and 76% of breast cancer patients respectively, while MMP-9 levels in these tissues did not differ significantly. The concentrations of MMP-2 and MMP-7 in blood serum were not associated with corresponding tumor values, did not exceed the control levels, and did not decrease after the excision of primary tumor. Serum MMP-9 was significantly decreased in breast cancer patients as compared to control group, and increased post-surgically in 85% of the patients. No unambiguous associations between the parameters studied and breast cancer clinico-morphologic prognostic factors were revealed.

Here we present the results of comparative immunoenzyme assay of the initial serum levels of VEGF in breast cancer patients (stages T1N0M0 and T2N0M0) and apparently healthy women (controls). It was found that VEGF concentrations in the serum of patients with breast cancer stages T1N0M0 and T2N0M0 significantly surpassed the control levels. Increased levels of VEGF surpassing the threshold values were more often observed in patients with T2N0M0 breast cancer compared to patients with T1N0M0 tumor. At the same time, this marker cannot be used in the diagnostics of this disease because in only 21.4% patients serum level of VEGF surpassed the upper boundary for this growth factor observed in the serum of control women. Serum concentration of VEGF in patients with stages T1N0M0 and T2N0M0 breast cancer did not depend on patient's age and reproductive function and receptor status of the primary tumor (estrogen and progesterone receptors), but was closely associated with tumor histogenesis and differentiation degree. Significantly higher levels of VEGF were observed in patients with lobular infiltrative breast carcinoma compared to patients with ductal tumors and in patients with low-differentiated tumors compared to highly and moderately differentiated tumors. High initial concentrations of VEGF (>300 pg/ml) were more often detected in patients with T2N0M0 breast cancer developing relapses within the first 3 years of follow-up compared to patients without relapses during the corresponding period (p=0.001). These findings suggest that serum level of VEGF in patients with T2N0M0 breast cancer before treatment can be used as an additional marker in parallel with standard clinical and morphological signs of the disease for more precise prognosis of early relapse (during the first 3 years of follow-up).

The content of matrix metalloproteinases (MMP) -2, -7, and -9 was significantly higher in tumors in comparison with the adjacent histologically intact gastric mucosa in 80, 70, and 72% patients with gastric cancer, respectively, the increase in the level of MMP tissue inhibitor-2 (TIMP-2) detected in 61% tumors was insignificant. Only plasma level of MMP-7 was elevated in primary patients in comparison with the control and positively correlated with the expression of this protein in the tumor. The concentration of MMP-7 was maximum in the blood of patients with tumor invasion in lymph vessels. These data suggest MMP-7 as a possible serological marker of gastric cancer.

Immunoenzymatic investigation demonstrated elevation of urokinase type plasminogen activation (uPA level) accompanied by an increase of PAI-1 level in oral cavity carcinomas as compared to adjacent mucosa. No statistically significant associations were revealed between the levels of the proteins studied and such prognostic factors as localization, growth form, histological structure and differentiation grade of primary tumor, its size and spread, lymph node involvement, disease stage.

Data are described on a retrospective immunohistochemical study of the Ki-67, PCNA, Bcl-2, BAX, BclX and VEGF expression in tumors of two groups of patients with breast cancer (BC) and with the favorable and unfavorable clinical courses. A reliably high level of VEGF expression was detected in tumors of patients with an early BC relapse. Apart from VEGF, higher levels of the Ki-67 and PCNA expression were registered in tumors of the discussed patient's category. It can be suggested that the expression parameters of VEGF, Ki-67 and PCNA in the primary tumor can be made use of in evaluating the BD prognostications or describing the features of high-risk groups with a high probability of early disease relapses.

We carried out a retrospective immunohistochemical study of Ki-67, PCNA, Bcl-2, BAX, BclX, and VEGF expression in tumors of two groups of breast cancer patients with favorable and unfavorable course of the disease. Considerably enhanced VEGF expression was detected in tumors of patients with early relapses of breast cancer. High VEGF expression was paralleled by high level of Ki-67 and PCNA expression in tumors. It can be hypothesized that expression of VEGF, Ki-67, and PCNA in primary tumor can be used for predicting the course of breast cancer or detecting the patients at a high risk of early relapses.