Lymphangiogenesis in Breast Cancer Tissue Detection and Its Reletionship with Clinicopathological Characteristics
|School||Hebei North University|
|Course||Pathology and Pathophysiology|
|Keywords||breast cancer nude mice transplantation lymphangiogenesis D2-40 CD31 CD34|
The aims of our study are as follows:to observe the morphological characteristics of lymphatics and to investigate the intratumoral lymphangiogenesisin transplantation tumor model of human breast infiltrating duct carcinoma in nude mice. Electron microscopy the morphology and characteristics of the tumor in and around the lymphatic of human breast cancer, to explore whether there are a nascent lymphatic vessels and lymphatic distribution of breast cancer within the organization. D2-40, CD31and CD34marker of lymphatic and blood vessels in breast, cancer. To investigate D2-40of CD31CD34value of the micro lymphatic vessels in breast cancer detection and identification of lymphatic and blood vessels value; To tudy the density and distribution of lymphangiogenesis To investigate the relations of LMVD (Lymphatic microvessel density) correlated with patient age, tumor size, axillarylymph node metastases, grading, and molecular typing. Thus providing a strong basis for the study of breast cancer lymph node metastasisand clinical treatment to select the adjuvant treatment program and prognosis.Using adriamycin resistant human breast cancer cell lines for BALB/C Nude mice to establish human breast cancer in nude mice model with a total of18cases, application of transmission electron microscopy to observe the morphological features of newbornlymphatic microvessel. Using D2-40to mark the lymphatic, and examine characteristics and distribution characteristics under light microscopy in breast cancer tissue newborn lymphatics morphology. Collecting PLA line operation treatment and axillary lymph node dissection for breast cancer cases form2007 January to2010June in General Hospital of the Air Force, selecting the cases with complete clinical data,remove the preoperative neoadjuvant chemotherapy and radiotherapy cases. The selected cases were confirmed by pathology for invasive ductal carcinoma, and select other20cases of benign breast tumor as control case. Observe the morphological features of lymphatic microvessel with transmission electron microscope among30cases. All the cases were eosin hematoxylin stained (Hematoxylin and eosin, HE) and progesterone receptor (Progestogen receptor, PR), estrogen receptor (Estrogen receptor, ER), human epidermal growth factor receptor2(Human epidermal growth factor receptor-2, HER-2), cytokeratin5/6(Cytokeration5/6, CK5/6), epithelial growth factor receptor (Epidermal growth factor receptor, EGFR), D2-40, CD31, CD34, P63immunohistochemically stained. The immunohistochemical HER-2(++) were analyzed by fluorescence in situ hybridization (Fluorescence in situ hybridization, FISH) detection.According to tumor adenoid structure, cellular atypia, mitotic figures for histological score and histological grading; according to immunohistochemical findings of the tumors were divided into four molecular typies. Appling SPSS17.0statistical software to carry on the analysis, comparison and application between groups of multiple sample rate of χ2test and multiple variable analysis of variance,0.05for the testing standards, P<0.05for the difference was statistically significant.Confirmed by histopathology, modeling human breast cancer in nude mice, Observed under the light microscope and electron microscope there were newborn lymphatics around the nude breast tumor tissue, of which wall thinning lumen distension, irregular. In124cases of invasive ductal carcinoma of breast cancer nests almost no lymphatic microvessel was observed. The quantity of lymphatic in peripheral tissue of invasive ductal carcinoma of the breast cancer increased, modality irregular, lumen thin, some in occluded state, part of the expansion was obvious, cords or plexiform, around the cancer tissue into circular distribution, Located in the periphery of the tumor D2-40positive lymphatic lumen was open, the tumor located in the internal D2-40positive lymphatic lumen stenosis, occlusion of small, even absent, tumor lymphangiogenesis within visible tumor thrombus. CD31, CD34positive blood vessels in the tumor periphery and within all can be detected, and the distribution had no difference.The LMVD of no correlation with age under35years old,65years old,35-65, LMVD were14.897(?)2.508,13.753(?)4.253,11.959(?)3.3888, χ2=3.7692, P=0.1519, the difference had no statistical significantce. With the longest diameter increased, LMVD higher density, maximum tumor diameter less than or equal to2cm,2cm-5cm,>5cm LMVD was11.309(?)4.611,14.494(?)3.263,15.499(?)3.939,χ2=6.0046, P=0.0497, the difference was statistically significant. The higher histologic grade, the high LMVD was density, P=0.0000, histological grade for class Ⅰ,Ⅱ,Ⅲ and LMVD were11.235(?)4.700,13.766(?)3.423,17.466(?)3.392, the difference has statistical significance. Lymph node metastasis of LMVD was higher than that in lymph nodes without metastasis group, LMVD=13.111(?)4.199,14.623(?)3.763,P=0.0490, the difference was statistically significant. In each of LuminalA type, LuminalB type, Basal-like type, HER-2type of each type in the number of LMVD was respectively13.070,13.807,14.850,13.524. The worst prognosis of Basal-like breast cancer LMVD was the highest, followed by the poor prognosis of HER-2expression and prognosis, preferably of the LuminalA type LMVD was the minimum number of13.070, but the χ2=4.0394, P=0.2573, each type of LMVD was no significant difference.Therefore, there were newborn lymphatics in breast cancer tissue, which mainly distributed amound tumor surrounding tissue. Newborn lymphaties’s density was closely related to humor’s size and grade, counting lymphatic vessels in peripheral tissued, can help clinical judgement of prognosis, thus improving the survival rate of patients, and providing basis for the study of lymphatic metastasis.