Клинические перспективы исследования матриксных металлопротеиназ и их тканевых ингибиторов у больных раком яичников

Иммуноферментное исследование содержания матриксных металлопротеиназ (ММП) 2, 7, 9 и их тканевых ингибиторов (ТИМП) 1 и 2 типа в опухолевой ткани, сыворотке крови и асцитической жидкости больных раком, пограничными и доброкачественными новообразованиями яичников показало координированное увеличение тканевой экспрессии и сывороточной концентрации ММП-7 при раке яичников. Противоположная направленность изменений обнаружена для ММП-2. Изменения в показателях содержания ММП-9, ТИМП-1 и ТИМП-2 выражены в меньшей степени. Наиболее значимым серологическим маркером рака яичников следует признать ММП-7. Чувствительность этого теста относительно контроля при 95 %-ной специфичности составляет 78 %. Уровень ММП-7 также положительно коррелирует с ключевыми показателями распространенности рака яичников: стадией заболевания, размером первичной опухоли, наличием и характером диссеминации по брюшине и метастазов в большом сальнике, наличием и количеством асцита.

Clinical Prospects of Matrix Metalloproteinases and Their Tissue Inhibitors Study in Ovarian Cancer Patients

Matrix metalloproteinase (MMP) 2, 7, 9 and their type 1 and 2 tissue inhibitors (TIMP) levels were measured with standard ELISA kits in tumor extracts, blood serum and ascitic fluid of patients with ovarian cancer, benign and borderline ovarian neoplasms - 49, 24 and 11 patients respectively. Significant increase of MMP-7 content was revealed in ovarian cancer tissue as compared to benign and borderlaine tumors. The same trend was demonstrated for MMP-9, while MMP-2 and TIMP-2 were significantly decreased in cancer tissue as compared to benign ovarian lesions, and TIMP-1 did not differ between various types of ovarian neoplasms. Evaluation of the associations between the markers studied and clinico-pathologic features of ovarian cancer revealed no significant differences in MMPs levels depending on FIGO stage, but TIMP-1 level in stage III-IV tumors was significantly lower than in stage I-II (p=0.022). MMP-7 and MMP-2 levels were significantly higher in the tumors of patients with bilateral ovarian cancer than in those with unilateral lesion. No prominent associations with the character of ovarian cancer peritoneal dissemination, presence and size of metastases in greater omentum, as well as with the localization of distant metastases were found. All the markers were detected also in ascitic fluid. A negative association was revealed between the volume of ascites and its MMP-2 (R= −0.53; p=0.008) and TIMP-2 concentrations (R= −0.78; p=0.0002). And MMP-2 and MMP-7 concentrations in ascitic fluid were positively associated with corresponding tumor levels (R=0.55; p=0.013 and R=0.42; p=0.047 respectively). Positive associations were also found between tumor and serum concentrations of MMP-2 (R=0.31, p=0.020), MMP-7 (R=0.29, p=0.006) and MMP-9 (R=0.24, p=0.019). A significant increase of serum levels was demonstrated for MMP-7 and MMP-9 in ovarian cancer as compared to benign tumor patients and control group of 30 practically healthy women. On the contrary, MMP-2 level in blood serum of ovarian cancer patients was decreased. Statistical evaluation revealed that MMP-7 can be regarded as the most notable serological marker for differential diagnostics of ovarian cancer. The sensitivity of this test in relation to control group comprised 78 % (cut-off - 4,67 ng/ml) at 95 % specificity level. Serum MMP-7 level also positively correlated with the key indices of ovarian cancer extension: disease stage, size of primary tumor, presence and character of peritoneal dissemination and metastases in greater omentum, presence and volume of ascites, as well as with classical ovarian cancer marker CA-125 level.