Comparison of matrix proteinase mRNA expression in morphologically normal, neoplastic, andmetastatic colon tissue and colon biopsies from healthy donors

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. © 2018 Russian Academy of Medical Sciences. All rights reserved

Molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer patients

Objective. To identify molecular genetic prognostic factors for metastatic regional lymph node involvement in breast cancer (BC) on the basis of the gene-expression profiling analysis of primary tumors. Subjects and methods. The investigation enrolled 200 patients with morphologically verified unicentric invasive BC (T1-4N0-3M0,) who had been treated at the Ulyanovsk Regional Clinical Oncology Dispensary in 2012 to 2015. A tumor tissue molecular genetic study was performed using reverse transcription-polymerase chain reaction (RT-PCR) assay; a diagnostic panel consisted of 28 functional genes. Results. In the metastatic regional lymph node involvement group, the primary breast tumor was characterized by enhanced proliferative activity in terms of the expression of the Ki-67 gene (p = 0.028) and by the higher mRNA levels of the NAT (p = 0.039) and CD68 (p <0.001) genes with a reduction in PTEN expression (p <0.001) and with decreased ESR1 gene expression (p = 0.043). A discriminant analysis showed that the accuracy in predicting the presence or absence of metastatic regional lymph node involvement on the basis of a primary tumor molecular genetic study using a 7-gene expression panel was 91.9 and 78.8%, respectively. Conclusion. The primary breast tumor tissue molecular genetic study involving a set of 7 genes (PTEN, CD68, CCNB1, MGB1, MYC, BCL2, and ESR1) can become an additional diagnostic tool for assessing the presence of metastatic lymph node involvement when planning the volume of axillary lymph node dissection in BC patients. © 2020, Bionika Media Ltd.. All rights reserved

Mammaglobin in peripheral blood and the tumor of breast cancer patients

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). 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. © 2016, Pleiades Publishing, Ltd

Mammaglobin in peripheral blood and the tumor of breast cancer patients

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). 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. © 2016, Pleiades Publishing, Ltd

Возможности типирования рака молочной железы с использованием методики ОТ-ПЦР

Introduction. Adjuvant systemic therapy remains one of the main options for treating breast cancer. Results of standard immunohistochemical studies are not always a criterion for selecting systemic therapy. Nowadays, multigene expression analysis is actively used to predict the response to chemotherapy in patients with early-stage breast cancer. We studied a 24-gene multi-gene panel for typing breast cancer. Material and Methods. A prospective analysis of 199 breast cancer patients (T1-3N0-3M0) was carried out. Surgical specimens were studied using the standard immunohistochemistry (IHC) and RT-PCR for detecting expression of 24 genes. Results. According to the IHC results, breast cancer was divided into 5 molecular subtypes: luminal A was detected in 59 (30 %) patients; luminal B (HER2-negative) in 52 (26 %); luminal B (HER2-positive) in 19 (9 %); triple-negative in 28 (14 %); HER2-positive 41 (21 %). RT-PCR showed that STK15, MYC, MYBL2, BIRCC5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 and MMP11 were the most significant genes in subtype distribution. The total percentage of matches between the two studies was 61.7 %. Conclusion. Studies have shown the need to add additional typing methods for breast cancer to a standard IHC study, which will undoubtedly increase the information content of diagnostic measures and will improve the effectiveness of the treatment.Введение. Адъювантная системная терапия остается одним из основных методов лечения у больных раком молочной железы. Результаты стандартного иммуногистохимического исследования не всегда в полной мере являются критерием для выбора системной терапии. Для прогнозирования эффективности лечения при ранних стадиях активно применяется мультигенный экспрессионный анализ. Была изучена отечественная мультигенная панель, состоящая из 24 генов, позволяющая типировать рак молочной железы. Материал и методы. Проводился проспективный анализ 199 больных РМЖ (T1-3N0-3M0), в ходе которого операционный материал подвергался стандартному иммуногистохимическому исследованию, а также он изучался методом ОТ-ПЦР с выявлением экспрессии 24 генов. Результаты. По результатам ИГХ осуществлялось молекулярное типирование РМЖ с выделением 5 подтипов: люминальный тип А был выявлен у 59 (30 %) больных; люминальный В (HER2-негативный) -у 52 (26 %); люминальный В (HER2-позитивный) - у 19 (9 %); трижды негативный - у 28 (14 %); HER2-позитивный - у 41 (21 %) пациента. По данным ОТ-ПЦР наиболее значимыми генами в распределении на подтипы рака молочной железы являлись: STK15, MYC, MYBL2, BIRCC5, BCL2, TERT, ESRP1, PGR, HER2, GBR7, MGB1 и MMP11. При дальнейшем анализе суммарное число совпадений данных двух исследований составило 61,7 %. Заключение. Проведенные исследования продемонстрировали необходимость добавления дополнительных методов типирования рака молочной железы к стандартному ИГХ-исследованию, что, несомненно, повысит информативность диагностических мероприятий и позволит повысить эффективность проводимого лечения

Маммология

Основная цель краткого издания руководства - познакомить аудиторию с последними достижениями медицинской науки и практики в решении проблем заболеваемости молочной железы, базирующимися на междисциплинарной интеграции онкологии, рентгенорадиологии, гинекологии, технологий системной биологии, открывающей перспективы распознавания путей канцерогенеза и создающей возможности для адекватной и своевременной борьбы за снижение смертности от онкологических заболеваний. Одной из задач настоящего издания является повышение онконастороженности врачей в отношении рака молочной железы. В книге предложен эффективный алгоритм обследования пациенток с подозрением на рак молочной железы и выработки оптимального маршрута от врача, обнаружившего первые симптомы, до специалиста-онколога, занимающегося лечением, профилактикой и реабилитацией. В руководстве представлен также современный уровень диагностики и лечения доброкачественных заболеваний молочных желез консервативными средствами с использованием стационарозамещающих технологий. Издание предназначено врачам-онкологам, хирургам, радиотерапевтам, химиотерапевтам, генетикам, рентгенологам, специалистам по ультразвуковой диагностике, акушерам-гинекологам, патологоанатомам, врачам общей практики и другим специалистам, а также студентам, ординаторам и аспирантам медицинских вузов