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Pilot Study Of Vasculogenic Mimicry In Gastric Adenocarcinoma

Posted on:2011-07-22Degree:MasterType:Thesis
Country:ChinaCandidate:X Q WangFull Text:PDF
GTID:2154330332974337Subject:Pathology and pathophysiology
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Background: Vasculogenic Mimicry (Hereinafter shortly as VM) is newly termed for tumour blood vessel formation. Its characters are as follows: no endodermal cell cover in lumen; lumen-like construction is formed through tumor cells self-transmutation and the interaction with the extracellular matrix (ECM), while blood is floating in this type of lumen. Thus, tumour cells are provided with blood to meet the needs of its growth, invasion and metastasis. Presently, VM has been proved being existing in some highly aggressive malignancies. Such as: Inflammatory breast cancer, aggressive ovarian cancer, leiomyoma etc. And there is abundant researches show that VM is a functional circle in some severe malignancies'tissues. With the barrier of endodermal cell, tumor cells are able to contact blood directly. Therefore, the clinical characteristic of malignancies VM is extensive hematogenous metastasis in early stage, and the tumor suffering patients'prognosis is grim. Gastric adenocarcinoma is one of very common human malignancies. Since the early symptoms are obscure, the malignancies often have reached the terminal stage when discovered. Removal surgery is the treatment mostly used under such situation, though the patients'survival rate within 5 years has not been significantly increased. Local recurrence and metastasis & spread after surgery are the main causes of death. At present, the research of malignancy blood providing channels mainly focuses on the aspect of tumor abduction angiogenesis. It is worth further research on whether VM exists in gastric adenocarcinoma and its mechanism and clinical significance since there is no report on that field so far. Objectives: Through the review on the specimen of paraffin embedded tissues, we observe and proved if the VM unique tumour blood providing model exists in the tissues of gastric adenocarcinoma, and analyze the relationship between the VM and patients'clinical pathology index, and also expatiate the clinical pathology significance of the VM. Inspect further the expressions of MMP-2, HIF-1α, and Ki67 in the tissues of gastric adenocarcinoma; preliminarily discuss their roles and functions in the formation of VM in gastric adenocarcinoma. The research aims at providing academic fundamental for study on the molecule mechanism of VM formation in gastric adenocarcinoma, simultaneously, providing academic evidence and possible predictable index for forecasting the tumour's invasion and metastasis in order to guide clinical treatment and prognosis.Methods:1. 121 samples (full data, acquired from January 2006 to March 2008), of poorly & moderately differentiated gastric adenocarcinoma collected from Anhui Provincial Xin'an Hospital, were diagnosed through HE chromosome sections as gastric adenocarcinoma. Through inspecting HE sections and CD34/PAS double staining protocol, we observed and proved if there was VM in gastric adenocarcinoma, and expatiated VM's clinical pathology significance.2. With the adoption of immunohistochemistry, we tested the expressions of MMP-2, HIF-1α, and Ki67 in gastric adenocarcinoma, and analyzed the connections between the expressions and the patients'clinical pathology index. We compared the above index expression rate difference between VM positive group and VM negative group and the connection between the above indexes, and primarily discussed their roles in the formation of VM. Results:1. 121 patients with gastric adenocarcinoma, 44 cases (36.36%) were found VM. Observed by HE stained mirror, pipe-like structures are surrounded by tumor cells, red blood cells exist within the pipeline, the tumor cells are surrounded by red blood cells, no cover of endothelial cells lining exsit, no necrotic disintegration of tumor cells and inflammatory cells exsit in the lumen. CD34 and PAS double staining show a layer of PAS positive material that Surrounds basement membrane-like structure to separate tumor cells and red blood cells, tumor cells CD34 staining that surround the lumen show negative, which confirms that it is not endothelial cells2. VM formation is of no statistical significance in patients'sex and age difference(P>0.05), while is statistically significant in tumor size, histological grade, nests or cords arranged when poorly differentiated(P<0.05 or P<0.01)3. The results of immunohistochemistry show MMP-2, HIF-1α, Ki67 positive expression rate is 90.08%, 62.80%, 76.03% respectively in gastric adenocarcinoma. The expression of MMP-2 is statistically significant in whether lymph node metastasis exsit or no(tP<0.05). The expression of HIF-1αis statistically significant in degree of tumor differentiation and whether lymph node metastasis exsit or not(both P<0.01)The related analysis indicates that MMP-2 expression and HIF-1αexpression are positively correlated in gastric adenocarcinoma(r=0.317,P<0.01).The MMP-2 high expression rate and HIF-1α,Ki67 positive expression rate of VM-positive group is obviously high than that of VM-negative group(P<0.05 or P<0.01).Conclusions:1. VM exists in gastric adenocarcinoma. VM is a unique pattern of blood supply for some High-invasive tumors, which could connect with the host blood vessels pass. Thus it can remodel tumor microcirculation, offer enough blood supply to tumors and meet the needs of tumors growth, invasion and metastasis. 2. In gastric adenocarcinoma, the formation of VM is closely linked to the accretion, differentiation decrease of the tumor and lymph follicle metastasis3. Immunohistochemistry Staining results show that in VM-positive group of gastric tumor, the high expression rate of MMP-2 and positive expression rate of HIF-1α, Ki67 is obviously higher than that in VM-negative group, which indicates that cancer cells of VM gastric adenocarcinoma have more proliferative activity and tumor cells in gastric adenocarcinomacan promote the formation of VM in the way that HIF-1αregulates the expression of MMP-2 .
Keywords/Search Tags:gastric, adenocarcinoma/Vasculogenic, mimicry/Matrix, metalloproteinase-2/Hypoxia inducible factor-1α/Ki67, antigen/Immunohistochemistry
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