Search

Currently, no molecular biological markers do exist for early diagnosis of breast cancer. One of the possible candidates for the marker of early breast cancer is mammaglobin (MGB1) or SCGB2A2 (secretoglobin, family 2A, member 2), characterized by the maximal expression level in early breast cancer. Using the RT-PCR method MGB1 mRNA expression was examined in 57 tumor tissue samples and 57 samples of morphologically non-malignant tissue (MNT) of breast cancer (BC) patients. Specificity and sensitivity of the MGB1 mRNA assay in peripheral blood of BC patients was evaluated by nested PCR. 169 blood samples (from 95 BC patients, 22 from patients with benign breast tumors, 28 from patients with tumors of other localizations, and 24 samples from healthy donors) have been analyzed. MGB1 expression was significantly higher in BC tissue samples compared to MNT (p=0.0019). The maximal expression level was in the samples T1 (p=0.013), stage I BC (p=0.037), GI (p=0.0019). The MGB1 expression positively correlated with expression of estrogen (p = 0,034) and progesterone (p=0.0004) receptors. Sensitivity and specificity of the MGB1 mRNA assay in peripheral blood were 60.6% and 92.3%, respectively. Expression of MGB1 was higher in BC than MNT and it decreased during BC progression. The sensitivity and specificity of the MGB1 mRNA assay may be used as an additional diagnostic method.V nastoiashchee vremia ne sushchestvuet molekuliarno-biologicheskikh markerov dlia diagnostiki rannego raka molochnoĭ zhelezy (RMZh). V kachestve vozmozhnogo markera rassmatrivaetsia mammaglobin (hMAM), uroven' ékspressii kotorogo maksimalen pri rannem RMZh. C pomoshch'iu metoda OT-PTsR opredelen uroven' ékspressii mRNK mammaglobina v 57 parnykh obraztsakh opukholevoĭ i morfologicheski neizmenennoĭ tkani (MNT) molochnoĭ zhelezy, poluchennykh ot bol'nykh RMZh. Otsenena spetsifichnost' i chuvstvitel'nost' analiza mRNK hMAM v perifericheskoĭ krovi bol'nykh RMZh metodom gnezdnoĭ PTsR. Proanalizirovano 169 obraztsov krovi (95 ot bol'nykh RMZh, 22 ot bol'nykh s dobrokachestvennymi opukholiami molochnoĭ zhelezy, 28 ot bol'nykh s opukholiami drugoĭ lokalizatsii i 24 obraztsa zdorovykh donorov). Ékspressiia hMAM byla znachitel'no vyshe v obraztsakh tkani RMZh po sravneniiu s MNT (r=0,0019). Maksimal'nyĭ uroven' ékspressii otmechen v obraztsakh T1 (r=0,013), stadii I (r=0,037), GI (r=0,0019). Vyiavlena polozhitel'naia korreliatsiia mezhdu ékspressieĭ hMAM i retseptorov éstrogena (p=0,034) i progesterona (r=0,0004). Chuvstvitel'nost' i spetsifichnost' opredeleniia ékspressii hMAM v perifericheskoĭ krovi sostavila 60,6 i 92,3% sootvetstvenno. Ékspressiia hMAM pri RMZh byla vyshe, chem v MNT i snizhalas' pri vysokoĭ rasprostranennosti zabolevaniia. mRNK mammaglobina obnaruzhena v 61% obraztsov krovi bol'nykh RMZh, v 22,7% – pri dobrokachestvennykh obrazovaniiakh molochnoĭ zhelezy i lish' v odnom obraztse krovi pri drugoĭ lokalizatsii opukholevogo protsessa – u bol'noĭ rakom legkogo. V obraztsakh krovi zdorovykh donorov mRNK mammaglobina ne obnaruzhena. Takim obrazom, opredelenie mRNK hMAM v perifericheskoĭ krovi, po-vidimomu, mozhno rassmatrivat' kak dopolnitel'nyĭ metod diagnostiki RMZh.

Matrix metalloproteinases (MMPs) responsible for the extracellular matrix remodeling, the activation of various growth factors, and angiogenesis play an important role in the colorectal cancer (CRC) development. In the present work the comparative analysis of MMP-7, -8, -9, and -11 mRNA as well mRNA of the Ki-67 proliferation marker in tissue samples obtained from CRC patients and healthy individuals. Employing the real time PCR method the expression levels of several MMPs (MMP-7, -8, -9, and -11) and cell proliferation marker, Ki-67, were simultaneously measured in 256 tissue samples obtained from 112 patients with CRC: 112 samples of the primary tumor (CRC), 112 samples of the most distant border of morphologically normal colonic mucosa (MNT), 16 samples of liver metastases) and from 16 healthy volunteers who underwent colonoscopy and biopsy. The expression of both MMPs studied and Ki-67 was found to be elevated in CRC primary tumors and liver metastases compared with the normal mucosa. CRC tumor and metastatic cells exhibited similar proliferative activity. The metastases are characterized by the highest cross-correlation of MMPs among tissue types tested. For the first time it was shown that normal mucosa from healthy individuals and CRC patients varied in the MMP-8 expression level. They also had dissimilar MMP correlation patterns thus suggesting that epithelial cells adjusted to CRC tumor differ from mucosal epithelial cells of healthy individuals.Matriksnye metalloproteinazy (matrix metalloproteinases, MMP), otvechaiushchie za remodelirovanie vnekletochnogo matriksa, aktivatsiiu razlichnykh rostovykh faktorov i angiogenez, igraiut vazhnuiu rol' v razvitii kolorektal'nogo raka (KRR). V dannoĭ rabote proveden sravnitel'nyĭ analiz urovneĭ ékspressii mRNK MMP-7, -8, -9 i -11, a takzhe markera proliferatsii Ki-67 v obraztsakh tkaneĭ, poluchennykh ot patsientov s KRR i zdorovykh donorov. S ispol'zovaniem metoda PTsR v real'nom vremeni byli issledovany urovni ékspressii ikh mRNK v 256 obraztsakh tkani, poluchennykh ot 112 patsientov s KRR: 112 obraztsov pervichnoĭ tkani opukholi (KRR), 112 obraztsov morfologicheski normal'noĭ tkani slizistoĭ stenki tolstoĭ kishki (MNT), udalennoĭ ot pervichnoĭ opukholi na 15-20 sm i 16 obraztsov metastaticheskoĭ opukholi KRR v pecheni (MP). Takzhe issledovany 16 bioptatov, poluchennykh vo vremia protsedury kolonoskopii u zdorovykh volonterov (NT). Vyiavleno, chto ékspressiia mRNK genov, kodiruiushchikh MMP i Ki-67, vozrastaet v pervichnoĭ tkani KRR i MP po sravneniiu s MNT i NT. Pri étom kletki pervichnoĭ tkani opukholi i kletki metastazov imeiut skhodnuiu proliferativnuiu aktivnost'. Sredi issledovannykh tipov tkaneĭ metastaticheskaia opukhol' kharakterizuetsia naibol'shim chislom i siloĭ pozitivnykh korreliatsiĭ mezhdu urovniami ékspressii mRNK genov, kodiruiushchikh MMR. Vpervye pokazano, chto normal'naia tkan' slizistoĭ obolochki kishki patsientov s KRR i zdorovykh donorov razlichaiutsia po urovniu ékspressii mRNK MMP-8. Krome togo, oni imeiut raznye korreliatsionnye patterny issleduemykh MMR, chto svidetel'stvuet o znachitel'nykh otlichiiakh mezhdu kletkami normal'noĭ tkani, sosedstvuiushcheĭ s opukhol'iu, i kletkami slizistoĭ obolochki kishki zdorovykh donorov.

Extracellular glycoproteins of the laminin family are essential components of basement membranes involved in a number of biological processes, including tissue differentiation, wound healing, and tumorigenesis. We present the first comprehensive study of promoter methylation status of the genes encoding laminin chains in normal tissues (peripheral blood leucocytes, buccal epithelial cells, autopsy breast tissue samples) and in breast carcinoma samples. Based on the results of this study, we divide laminin genes into three categories. Genes, constitutively methylated in breast tissues include LAMA3A, LAMB2, LAMB3, and LAMC2. Genes prone to abnormal methylation in breast carcinoma include LAMA1, LAMA2, LAMA3B, LAMA4, LAMB1, and LAMC3. Genes that are rarely if ever methylated in breast carcinoma include LAMA5 and LAMC1. The constitutively methylated group includes all of the genes that encode subunits of laminin-5 (the historical name of laminin 332), the promoters of which were previously considered unmethylated in normal tissues and prone to abnormal methylation in breast cancer.