Angiogenesis is a key factor of tumor progression. Considering, that the tumor vessels are heterogeneous and differ in morphology and clinical significance, the purpose of this research was to study of the morphological features of tumor vessels and their relationship with the clinical characteristics and morphological features of breast cancer (BC). In this pilot study the tumor samples received from 59 patients with T1–T2 stages of ductal invasive carcinomas were included. The sections were stained with hematoxylin and eosin and immunohistochemically using antibodies to CD34. The morphological features and the number of different types of tumor vessels were assessed microscopically and were compared with grade, lymph node metastasis, hormone receptors, HER2/neu status and with the presence of tumor emboli in vessels (lymphovascular invasion). We identified the following types of tumor vessels in BC: the normal microvessels, the dilated capillaries of peritumoral stroma, the atypical dilated capillaries and the “cavitary” structures (CS) type-1 and type-2 relating to the “cavitary” type of angiogenesis that was described by us earlier. The number of dilated capillaries correlated with CS type-1 (p = 0.003), CS type-2 (p = 0.002), atypical dilated capillaries (p = 0.0008) and with lymphovascular invasion (p = 0.005); the presence of atypical dilated capillaries—with CS type-1 (p < 0.00001), CS type-2 (p = 0.00004), lymphovascular invasion (p = 0.0002) and with the tumor grade (p = 0.003); the number of CS type-1—with estrogen receptor (p = 0.002) and progesterone receptor (p = 0.002) status and with lymphovascular invasion (p = 0.004); the presence of CS type-2—with positive Her2/new status (p = 0.0002) and lymphovascular invasion (p = 0.01). The density of normal microvessels was not associated with other types of tumor vessels and with clinical characteristics of BC. These data indicate that varied types of tumor vessels are associated with different morphological characteristics of BC, such as hormone receptors and HER2/neu status, lymphovascular invasion. We believe that the atypical dilated capillaries are related to the “cavitary” type of angiogenesis. The strong correlations of lymphovascular invasion with CS type-1 and atypical dilated capillaries testify that the “cavitary” type of angiogenesis may play a significant role in the formation of tumor emboli in the vessels.
Previously, we have shown the possibility of intramucosal gastric carcinoma induction by the intragastric administration of a mixture of formaldehyde and hydrogen peroxide in rats. In this study, we report a sizable increase in carcinogenic properties of the mixture when a suspension containing calcium carbonate nanoparticles was added to it. This technique allowed us to reduce both the number of the carcinogen administrations from twelve to two and the time to the cancer induction from six to four months. Although the induced tumors were represented by the intramucosal carcinomas, they were characterized by the extensive invasion of individual tumor cells and their clusters into the muscle layer and serosa as well as into the omentum and blood vessels. Considering that the invasive tumor cells were positive for vimentin, Snail and TGF-β2, we concluded that their invasion was the result of the activation of epithelial–mesenchymal transition (EMT) mechanisms. Thus, taking into account the data obtained, it can be assumed that under the conditions of inflammation or carcinogenesis, the calcium carbonate nanoparticles may affect the activation of EMT mechanisms.
Цель исследования - изучение морфологии опухолевых сосудов и ее связи с клинико-морфологическими характеристиками и рецепторным статусом новообразования при раке молочной железы (РМЖ). Материалы и методы. Образцы опухолей 66 пациенток с T1-2 стадиями инвазивного РМЖ неспецифического типа окрашивали гематоксилином Майера и эозином, а также иммуногистохимическим методом с использованием антител к CD34. Результаты. Проведенное исследование позволило выделить следующие типы опухолевых сосудов: обычные капилляры, диля-тированные капилляры (ДК) перитуморальной стромы и атипичные дилятированные капилляры (АДК) интратуморальной стромы, характеризующиеся хаотичным расположением клеток эндотелиальной выстилки. Количество ДК в перитуморальной строме коррелировало с выраженностью лимфоидной инфильтрации стромы опухоли (р = 0,0001), количеством АДК (р = 0,0001) и наличием опухолевых эмболов в сосудах (р = 0,02); количество АДК - с отрицательным статусом рецепторов эстрогенов (р = 0,008) и прогестерона (р = 0,043) и наличием опухолевых эмболов в сосудах (р = 0,001). Выводы. Полученные результаты свидетельствуют о неоднородности сосудов по морфологии и клинической значимости при РМЖ.
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