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Expression Of CD44 Splice Variant 6 In Human Gastric Carcinoma And Precancerous Lesion

Posted on:2004-10-11Degree:MasterType:Thesis
Country:ChinaCandidate:H ShenFull Text:PDF
GTID:2144360092490677Subject:Internal Medicine
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Stomach cancer is one of the most frequent cancers in the world and account for one third of all cancer deaths in the Chinese population. The basical and clinical research on gastric carcinoma is always of importance. A sequence of transformation from chronic active gastritis to chronic atrophic gastritis, intestinal metaplasia, dysplasia and carcinoma for gastric carcinogenesis was hypothesized. It is important to identify the biologic markers that predict tumor progression. The acquistion of certain adhesion molecules by tumor cells, enabling them to enter the circulation and to extravasate from the endothelial surface is critically important in the process of tumor metastasis. Recently, CD44,a transmenbrane glycoprotein has been postulated to have a role in tumor metestasis. The gene encoding CD44 is found on chromosome 11p and comprise 20 exons. As an integral cell membrane glycoprotein, CD44exists in numerous isoforms which are generated from the primary transcript by "alternative splicing" of 10 exons (V1-V10). To date, at least 20 variants (V) of CD44(CD44V) have been identified, they are known to function in homing of lymphocytes, cell adhesion, activation of leukocytes, and migration of cells. Gunthert et al were the first to show that the expression of CD44V endowed a nonmetastatic line of cells with metastatic potential in a rat carcinoma modol. It since has been reported that the expression of CD44V correlate with tumor progression, metastasis, and prognosis in various carcinoma, e.g., renal, pleural, breast and various gastrointestinal tumors. In gastric carcinoma, the expression of CD44 splice variant 6 (CD44V6) was considered to be a risk factor for recurrence and poor prognosis. However the association between CD44V6 expression and gastric precancerous lesions, and its functional role in tumor progression has not yet been clarified. In the present study, we examined the expression of CD44V6 by immunohistochemistry (IHC) method in gastritis, precancerous lesions as well as gastric cancer, to evaluate its use as diagnostic marker.Materials and Methods98 biopsy specimens were obtained from the First Affiliated Hospital of Zhejiang University and the Hangzhou No.2 Hospital fromMarch 2001 to August 2002, including 30 superficial gastritis, 34 atrophic gastritis with intestinal metaplasia, 34 dysplastic gastric mucosa. 64 gastric carcinoma tissues were obtained from primary gastric carcinomous patients operated on in the same hospitals and the same period. None of the patients had received chemotherapy before surgery. 42 males, 22 females, mean 57.6 years old. 45 had lymph node metastases, 19 had no lymph node metastases. 28 had distant metastases, 36 had no distant metastases. All specimens were fixed in buffered formalin and embedded in paraffin. The expression of CD44 splice variant(CD44V6) was analyzed by immunohistochemistry (IHC) method . It was observed that the corelatoins of The expression of CD44V6 and the clinical and pathologic characteristics of gastric cancer. Immunoreactivity was graded as follows: (+) ≥5% of epithelial cells were stained (-) : no detectable expression or <5% of epithelial cells were stained.The Student-Newman-Keuls test was used to determine which group was different from the others.We considered differences significant at P<0.05.ResultsThe positivity rate of CD44V6 in superficial gastritis, atrophy gastritis with intestinal metaplasia, dysplastic gastric mucosa and gastriccancer tissues were 3.33%(1/30),14.71%(5/34), 44.12%(15/34) and 60.94% (39/64) respectively. The positivity rates were significant higher in dysplastic gastric mucosa and gastric cancer tissue than those in superficial gastritis and atrophy gastritis mucosa with intestinal metaplasia (P<0.01). The expression of CD44V6 was related to distant metastasis(P<0.05) and TNM stage(P<0.01). The positive rate of the group with lymphatic metastasis was highter than that of the group without lymphatic metastasis, but had no significant differences (P>0.05) between them. No s...
Keywords/Search Tags:gastric carcinoma, Precancerous lesion, CD44 splice variant 6(CD44V6), immunohistochemistry
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