Dissertation
Dissertation > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Gallbladder disease

Study on the Expression of Marker Proteins of Cancer Stem Cell and the Metastatic and Invasive Mechamism in the Benign and Malignant Lesions of Gullbladder

Author HuangJiangSheng
Tutor ZhangYangDe
School Central South University
Course Surgery
Keywords Gallbladder cancer Gallbladder polyps Chronic cholecystitis Cancer stem cells Prostate stem cell antigen Oct-4 CD24 CD44V6 Immunohistochemistry Angiogenesis Lymphangiogenesis Capillaries, counting Lymphatic , Count Metastasis suppressor gene class KAL-1, Kiss-1 Metastasis-associated gene class MTA1 Adhesion molecule class , CD146 In situ hybridization
CLC R575.6
Type PhD thesis
Year 2009
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The first part of the cancer stem cells and their markers to study the purpose of research gallbladder adenocarcinoma, the epithelial paracancerous adenomatous polyps and chronic cholecystitis in prostate stem cell antigen (prostate stem cell antigen, PSCA), Oct-4 stem cell antigen (Oct-4 ), CD24 and CD 44V 6 expression levels, explore its clinical pathological significance and role in the development of mechanism in gallbladder adenocarcinoma. Methods 108 patients with gallbladder adenocarcinoma, 46 cases of cancer adjacent tissues, 15 cases of adenomatous polyps and 35 patients with chronic cholecystitis surgical specimens by 4% formaldehyde fixed in paraffin-embedded sections, PSCA, Oct-4, CD24 and CD the 44V 6 staining methods are Envision TM immunohistochemical footwork. Results (1) 108 cases of of gallbladder adenocarcinoma of PSCA and Oct-4, CD24 and CD 44V express positive cases were 59 cases (54.6%), 60 cases (55.6%), 57 cases (52.8 %) and 60 patients (55.6%), score values ??were 2.09 ± 1.94,2.06 ± 1.86,2.43 ± 1.65 and 2.52 ± 1.60; next to the 46 cases of cancer organizations PSCA, Oct-4, CD24 and CD 44V < / sub> 6 to express positive cases were 9 cases (19.6%), 10 patients (22.5%), 8 cases (17.4%) and 9 cases (19.6%), score values ??were 0.82 ± 1.11,0.85 ± 1.02, 0.78 ± 1.36 and 0.82 ± 1.39; 15 cases of adenomatous polyps PSCA, Oct-4, CD24 and CD 44V expressing positive cases were four cases (26.7%), 3 cases (20.0%) three cases (20.0%) and 4 patients (26.7%), score values ??were 0.74 ± 1.25,0.69 ± 1.32,0.72 ± 1.35 and 0.78 ± 1.28; 35 patients with chronic cholecystitis PSCA, Oct-4, CD24 and CD 44V 6 expression of the positive cases were 5 cases (14.3%), 5 patients (14.3%), 4 patients (11.4%) and 6 cases (17.1%), score values ??were 0.68 ± 1.21 , 0.67 ± 0.95,0.54 ± 1.44 and 0.58 ± 1.46; the PSCA, Oct-4, CD24 or (and) CD 44V 6 expression positive paracancerous organizations adenomatous polyps and chronic cholecystitis epithelium showed moderate to severe dysplasia; the gallbladder adenocarcinoma PSCA, Oct-4, CD24 and CD 44V 6 expression positive rates and scores significantly higher than in adjacent epithelial (PSCA, x 2 = 10.09, P lt; 0.01, τ = 4.23, Px 2 lt; 0.01 Oct-4, x 2 = 14.88, P lt; 0.01 , τ = 4.32, P lt; 0.01; CD24, x 2 = 16.58, P lt; 0.01, τ = 5.89, P lt; 0.01; CD 44V 6, x 2 = 16.90, P lt; 0.01, τ = 6.07, P lt; 0.01), adenomatous polyps (PSCA x 2 = 4.12, P lt; 0.05 τ = 2.60, P lt; 0.05; Oct-4, x 2 = 6.66, P lt; 0.01, τ = 280, P lt; 0.01; CD24, x 2 = 5.66, P lt; 0.05, τ = 3.78 P lt; 0.01; CD 44V 6, X 2 = 4.12, P lt; 0.05, τ = 4.05, P lt ; 0.01) and chronic cholecystitis (PSCA, X 2 = 17.40, P lt; 0.01, τ = 4.15, P lt; 0.01; Oct-4, x 2 = 18.16, P lt; 0.01, τ = 4.21, P lt; 0.01; CD24, x 2 = 18.48, P lt; 0.01, τ = 6.10, P lt; 0.01; CD 44V < / sub> 6, x 2 = 15.69, τ = 6.26, P (0.01). (2) adenoma or well-differentiated adenocarcinoma, maximal diameter of mass lt; 2cm, without lymph node metastasis and violations of the gallbladder outside surrounding tissue organ cases PSCA and Oct-4, CD24 and CD 44V 6 expression positive rates and scores poorly differentiated adenocarcinoma was significantly lower than the maximal diameter of mass ≥ 2cm, lymph node metastasis, and violations of the gallbladder outside surrounding tissues and organs cases, the differences were significant or highly significant sex (P lt; 0.05 or P lt; 0.01) (3) gallbladder adenocarcinoma PSCA, Oct-4, CD24 and CD 44V has a high degree of consistency (P lt; 0.01), its score between 6 expression levels between the close positive correlation (PSCAvs Oct-4, r = 0.44, P lt; 0.01; of PSCA vs CD24, r = 0.36, P lt; 0.01; PCSA vsCD 44V 6, r = 0.49; P lt; 0.01, Oct-4 vs CD24, r = 0.51, P lt; 0.01; Oct-4 vsCD 44V < / sub> 6, r = 0.39, P lt; 0.01; CD24 vs CD 44V 6, r = 0.48, P lt; 0.01). Conclusions PSCA, Oct-4, CD24 and CD 44V 6 as a cancer stem cell markers occur in gallbladder adenocarcinoma progression, metastasis and invasion potential has an important role, positive or high-level expression of poor clinical outcome; existence of cancer stem cells in cancer tissue may gallbladder gland play an important role in cancer development, and the impact of clinical biological behavior and prognosis of gallbladder adenocarcinoma; detect benign lesions of PSCA, Oct-4, CD24 and CD 44V 6 4 cancer stem cell markers physical expression levels of gallbladder cancer may have important clinical value of prevention and early detection of the first chapter of the second part gallbladder adenocarcinoma metastasis and invasion of regulation mechanism of gallbladder benign and malignant lesions microvascular and the purpose of the lymphatic counting its significance in gallbladder adenocarcinoma cancer tissue, adenomatous polyps and chronic cholecystitis microvascular (MV) and lymphatic vessels (LV) count and its clinical pathological significance. Methods 108 patients with gallbladder adenocarcinoma, 46 cases of cancer adjacent tissues, 15 cases of adenomatous polyps and 35 patients with chronic cholecystitis surgical resection specimens by 4% formaldehyde fixed in paraffin-embedded sections, MV and LV dyeing methods are SP immunohistochemical method, low magnification options MV and LV distribution richest 10 region, high magnification, count the number of MV and LV 10 regions, whichever is the mean for the case count value. Results 108 patients with gallbladder adenocarcinoma MV and LV count mean (64.2 ± 11.6,11.4 ± 5.2) was significantly higher than in adjacent tissue (28.2 ± 12.4, τ = 17.6, P lt; 0.01; 6.8 ± 6.2, τ = 4.63, P lt; 0.01), adenomatous polyps (32.4 ± 11.8, τ = 9.94, P lt; 0.01; 5.6 ± 2.9, τ = 0.49, P lt; 0.01) and chronic cholecystitis (22.2 ± 11.3, τ = 18.26, P lt; 0.01; 5.1 ± 3.9, τ = 6.63, P lt; 0.01). adenoma or well-differentiated adenocarcinoma maximal diameter of mass lt; 2cm without lymph node metastasis, and does not infringe the surrounding tissue, organ Case MV and LV count mean significantly lower than poorly differentiated adenocarcinoma, maximal diameter of mass ≥ 2cm, lymph node metastasis and invade surrounding tissues and organs of the cases (P lt; 0.01) gallbladder adenocarcinoma MV count LV count was close positive correlation (r = 0.38, P lt; 0.01). the conclusion MV and LV count may reflect gallbladder adenocarcinoma progress, the second chapter of the clinical markers of biological behavior and prognosis Objective To study the metastasis suppressor regulatory genes gallbladder adenocarcinoma, cancer tissue, adenomatous polyps and chronic cholecystitis KAI-1mRNA, Kiss-1mRNA, MTA1 and CD146 expression and its clinical pathological significance. 108 cases of gallbladder gland cancer adjacent tissues, 46 cases of cancer, 15 cases of adenomatous polyps and 35 patients with chronic cholecystitis tissues were fixed in 4% formaldehyde after routine paraffin-embedded sections, KAL-1mRNA the Kiss-1mRNA staining methods for in situ hybridization staining method, the MTA1 and CD146 staining method Envision TM two-step immunohistochemistry. Results (1) the gallbladder adenocarcinoma the KAL-1mRNA and Kiss-1mRNA, positive expression rate (51.9%, 53.7%) is significantly lower than adjacent tissues (KAL-1 mRNA, 80.4% x 2 = 11.02, P lt; 0.01; the Kiss-1mRNA, 82.6% x 2 = 11.48, P lt; 0.01), adenomatous polyps (KAL-1mRNA, 86.7%, x 2 = 6.48, P lt; 0.05; Kiss-1mRNA, 86.7%, x 2 = 5.86P lt; 0.05) and chronic cholecystitis (KAL-1 mRNA, 85.7% x 2 = 12.64, P lt; 0.01; Kiss-1 mRNA, 85.7% x 22 = 11.44, P lt; 0.01); the the gallbladder adenocarcinoma MTA1 and CD146 expression positive rate (48.1%, 53.7%) was significantly higher than the adjacent tissues (MTA1, 26.1%, x 2 = 6.46, P lt ; 0.05; CD146, 30.4% x 2 = 7.02, P lt; 0.01), adenomatous polyps (MTA1, 20.0% x 2 = 4.22, P lt ; 0.05; CD146, 20.0% x 2 = 8.59, P lt; 0.01) and chronic cholecystitis (MTA1, 8.6% x 2 = 13.31, P lt; 0.01, CD146, 5.7%, x 2 = 25.00, P lt; 0.01). (2) adenoma or well-differentiated adenocarcinoma, maximal diameter of mass lt; 2cm without lymph node metastasis, and does not infringe cases of the surrounding tissue and organs KAL-1mRNA, Kiss-1mRNA expression were significantly higher than poorly differentiated adenocarcinoma, maximal diameter of mass ≥ 2cm, lymph node metastasis, and invasion of surrounding tissues and organs of the cases (P lt; 0.05 or P lt; 0.01), but MTA1 the KAL-1mRNA, Kiss-1mRNA and CD146 expression in gallbladder adenocarcinoma expressed the opposite (P lt; 0.05 or P lt; 0.01). (3) KAL-1 mRNA and / or the Kiss-1mRNA express positive the gallbladder adenocarcinoma of MV and LV The count was significantly lower than the negative expression cases (P lt; 0.01); MTA1 and / or CD146 expression a positive gallbladder adenocarcinoma MV and LV count was significantly higher than that of cases with negative expression (P lt; 0.01). conclusion the KAL-1mRNA, Kiss-1 mRNA MTA1 reflect gallbladder adenocarcinoma, progression, clinical biological behavior and prognosis molecular markers are important regulatory gallbladder and CD146 expression levels are an important indicator, which may relate to the regulation of tumor metastasis and invasion capacity tumor angiogenesis and lymphatic generate relevant.

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