| A decline in the incidence of gastric cancer has been observed worldwide, but it is still the second commonest cancer. It is also the second cause of death resulted from cancers.The situation in China is unexceptional. Generally speaking, the overall prognosis of gastric cancer is poor. The five-year survival rate for early gastric cancer is up to 95%, while that of advanced cancer is less than 10%. TNM stage is still the most important prognostic factor by now. Histologic features are also important indicators of tumor prognosis. Watanabe and colleagues found a rare type of poorly-differentiated gastric cancer with distinct clinicopathological features and good prognosis. They are sometimes also called gastric medullary cancer for their morphological features are similar to those of breast medullary cancer. Colorectal medullary cancers are noted for their rich intraepithelial lymphocytes and RER+ phenotype. In gastric medullary cancers, no such studies have been reported yet.From the view of recent molecular biology advances in gastric cancer, three molecular models of gastric carcinogenesis were suggested: mutator pathway, chromosomal instability pathway (CIN) and mutations or epigenetic alterations of E-cadherin(ECD). Mutator pathway is caused by mutations or promotor CpGs hypermethylations of mismatch repair genes (MMR) and characterized as microsatellite instability-high phenotype. CIN is phenotyped as loss of heterezygosity (LOH) which infers inactivations of several tumor suppressor genes. As an important intercellular adhesion molecule, BCD also takes part in signal transduction via binding to -catenin. Gastric cancers, especially those of diffuse poorly differentiated type, exhibit reduced or abnormal ECD expression, underlying mutations or promotor hypermethylations in this gene.According to the status of microsatellite loci alterations, microsatellite instability (MSI) wasdevided into microsatellite instability-high frequency (MSI-H), microsatellite instability-low frequency (MSI-L) and microsatellite instability stable (MSS). Replication error positive (RER+) was suggested to take the place of MSI-H and replication error negative (RER-) for MSI-L and MSS. Bat26 was proven to be an identifier of MSI-H or RER+ status by our previous studies and other's. Apart from direct sequencing, most of present methods for MSI detection are based on polyacrymide gel electrophoresis. These methods were not suitable for wide clinical applications because of effort-and-time-consuming, high demands for technique, enviromental contaminations, health risks, and so on. Denatured high performance liquid chromatograph (DHPLC) can detect DNA or RNA by means of ion pair reverse phase HPLC principle. Under the non-denatured situations (50癈), DHPLC could be used for MSI analysis since DNA fragments are separated according to their length variations.Eighty-one gastric cancers, consisting of 35 fresh and 46 pararffin cases, were selected for study. All 17 medullary cancers from 612 gastric cancers between January 1994 and June 2002, and 64 non-medullary cancers were included randomly. Clinicopathological features of all cases were obtained via review of medical records and HE slides. Follow-up data of 64 cases were obtained. Tumor associated inflamatory cells, such as lymphocytes, mast cells, histiocytes, eosonophils and neutrophils, were observed and counted in HE or immunohistichemical stained slides (CD20, CD3, CD68 and Trypase). The expressions of P53, BCD and O6-Methyl-guanine methyl transferase (MGMT) were evaluated by semi-quantitative method. D1S199, D1S548, D1S552, D5S346, WIAF481, TP53, IGFIIR(G)8,, IGFIIR(CT)5, TGFJ3RII(GT)3, TGF RII(A)10, hMSH3(A)8, hMSH6(G)8, BAX(G)8, Bat26(A)26 and Tcf4(A)9, a panel of 15 microsatellite loci, were analyzed by polymerase chain reaction (PCR)-single strand length polymorphism (SSLP)-silver stain in fresh samples. Four loci, D1S548, D5S346, TP53 and Bat26, were dectected in paraffin cases by manual microdissection. Bat26+ was regarded as RER+. Thirty-two matched Bat26... |
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