Relationship between serosal invasion types and lymph node metastasis after total gastrectomy in gastric cancer and its significance in selection of rational dissection / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the relationship between serosal invasion types and lymph node metastasis after total gastrectomy in gastric cancer patients, and explore its significance in planning practice rational dissection based on the serosa types of gastric cancer during surgery.</p><p><b>METHODS</b>A total of 73 gastric cancer patients, who underwent total gastrectomy and lymph node dissection, were included in this study, and their clinicopathological data were analyzed. The serosa of gastric cancer was divided into five types: normal, reactive, nodular, tendonoid, and color-diffused, then they were combined into 3 groups: group 1: normal and reactive, group 2: nodular (including protruding nodular and flat nodular), and group 3: tendonoid and color-diffused. The lymph node metastasis ratios in the 3 groups were compared. The lymph nodes in each of the 3 groups were divided into 16 subgroups and the lymph node metastasis ratios of each subgroup in the 3 groups were compared and analyzed.</p><p><b>RESULTS</b>The lymph node metastasis ratio of the gastric cancer with normal and reactive type serosa was 5.3% (26/492), the nodular was 37.1% (250/673), the tendonoid and color-diffused was 50.0% (486/972). The lymph node metastasis ratio of normal and reactive type groups was the lowest, that of the tendonoid and color-diffused groups was the highest, and the nodular type in between, showing a statistically significant difference (P<0.01). The results of comparing the lymph node metastasis ratios from the 1st to 16th subgroup in the 3 groups showed the same trend (P<0.05).</p><p><b>CONCLUSION</b>Among all serosa types of gastric cancer, the lymph node metastasis ratio of the tendonoid and color-diffused is the highest, the normal and reactive type is the lowest, and the nodular in between. The extent of rational dissection should be carried out on the basis of serosa types of gastric cancer during surgery. An extended dissection including D2 and D3 lymphadenectomy should be performed for the patients with tendonoid and color-diffused serosa, a rational decreased operation including D1-D1+ lymphadenectomy should be performed for those with a normal and reactive type serosa, and for the patients with nodular type serosa, we suggest performing standard D2 dissection.</p>

Features of metastasis in different lymph node groups and their significance in lymph node dissection in total gastrectomy for gastric cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To summarize the features of metastasis in different lymph node groups (from 1 to 16 groups) in gastric cancer patients treated by total gastrectomy, and evaluate their clinical significance in lymph node dissection.</p><p><b>METHODS</b>The data of 73 gastric cancer patients with total gastrectomy and lymph node dissection from January 2004 to April 2006 were analyzed retrospectively. The lymph nodes were divided into 16 groups according to the 13(th) edition of gastric cancer treatment guideline of JGCA (The Japan Gastric Cancer Association). The metastatic rate and degree of dissected lymph nodes in these patients were compared.</p><p><b>RESULTS</b>The metastatic rates of lymph node groups in these patients from lower to higher were as follows: group 15, 13/16, 14v, 12, 10, 9, 11, 8, 2, 6/7, 5, 1, 4, 3. The lowest was the 15(th) group lymph nodes (1.4%), the highest was the 3rd group (65.8%), with a statistically significant difference between those two groups (P < 0.01). The metastatic degrees of the lymph node groups from lower to higher were as follows: 13, 16, 1, 7, 6, 5, 12, 4, 11, 8, 2, 15, 9, 3, 10, 14v. There was a statistically significant difference between the lowest group of lymph node (13(th) group, 10.7%) and the highest (14v(th), 56.3%, P < 0.01).</p><p><b>CONCLUSION</b>In the radical total gastrectomy for patients with gastric cancer, it is suggested that the regional lymph nodes with higher metastatic rate should be resected necessarily, and the group with a higher metastatic degree should be dissected completely. If the result of sentinel lymph node biopsy in the 3(rd) or 14v(th) group is negative, the operation extent can be reduced. If positive, it should be extended. When the biopsy result in the 13(th) or 16(th) is positive, palliative operation may be indicated. However, if the biopsy result is negative in the 13(th) or 16(th), but positive in the 14v(th) group, extended operation is indicated.</p>

Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma / 现代生物医学进展

Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.

The"modification"Type Microsatellite Change in High Frequency Microsatellite Instability Colorectal Cancer Closely Relating to MLH1 and KRAS Mutation / 现代生物医学进展

Microsatellite instability(MSI)was defined according to the frequency of positive findings in a panel of MSI markers.High frequency MSI(MSI-H)was the phenotype in which repeat sequences were extraordinarily unstable, and was considered to be the bona fide phenotype of DNA mismatch repair defection. However base substitutions in some well studied oncogenes or tumor suppressors were reported to be uncommon in MSI-H tumors. To explore this obvious contradiction, the relationship between MSI and KRAS gene mutations were studied in a panel of 76 human colorectal carcinomas, the whole exon of MLH1 and MSH2 were sequenced for MSI-H tumors. KRAS gene mutation was confirmed by similar frequencies in tumors of different MSI status. Intriguingly, all of the KRAS mutant MSI-H tumors harbored sequence alterations in MLH1gene, which was a key player in DNA mismatch repair system. This implied that in MSI-H tumors carrying MMR mutations, KRAS mutation were frequently and almost exclusively occurred. Furthermore, these MMR mutants were uniformly carrying a unique "modification" + "jumping" type MSI, which was different to MSI-H tumors without MLH1 or MSH2 gene mutations. This study shaded lights on the heterogeneity of MSI-H tumors, and implied the connection between "modification" type MSI and DNA mismatch defection.

Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma / 现代生物医学进展

Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.

The"modification"Type Microsatellite Change in High Frequency Microsatellite Instability Colorectal Cancer Closely Relating to MLH1 and KRAS Mutation / 现代生物医学进展

Microsatellite instability(MSI)was defined according to the frequency of positive findings in a panel of MSI markers.High frequency MSI(MSI-H)was the phenotype in which repeat sequences were extraordinarily unstable, and was considered to be the bona fide phenotype of DNA mismatch repair defection. However base substitutions in some well studied oncogenes or tumor suppressors were reported to be uncommon in MSI-H tumors. To explore this obvious contradiction, the relationship between MSI and KRAS gene mutations were studied in a panel of 76 human colorectal carcinomas, the whole exon of MLH1 and MSH2 were sequenced for MSI-H tumors. KRAS gene mutation was confirmed by similar frequencies in tumors of different MSI status. Intriguingly, all of the KRAS mutant MSI-H tumors harbored sequence alterations in MLH1gene, which was a key player in DNA mismatch repair system. This implied that in MSI-H tumors carrying MMR mutations, KRAS mutation were frequently and almost exclusively occurred. Furthermore, these MMR mutants were uniformly carrying a unique "modification" + "jumping" type MSI, which was different to MSI-H tumors without MLH1 or MSH2 gene mutations. This study shaded lights on the heterogeneity of MSI-H tumors, and implied the connection between "modification" type MSI and DNA mismatch defection.