Correlation between the immunohistochemical expression of Matrix metalloproteinase -7 and CD34 and their role in gastric carcinoma (A clinicopathological study

number: 
2461
إنجليزية
department: 
Degree: 
Imprint: 
Medicine
Author: 
Mohannad Mahdi Abed-ali
Supervisor: 
Dr. Ala'a Ghani Hussain
year: 
2010

Abstract:

Carcinoma of the stomach is one of the most prevalent cancer types in the world today and a major killer world wide.MMP-7 is a member of the matrix metalloproteinases family that play important role in extracellular matrix degradation and hence tumor invasion, metastasis and facilitating tumor angiogenesis that allow tumors to grow and metastasize .understanding the role of MMP-7 in tumor growth, invasion, metastasis and angiogenesis is essential for better understanding of tumor genesis, tumor progression ,prognosis, and antitumor therapy. The aim of the study: 1-To assess the immunohistochemical expression of MMP-7 and CD34 in gastric carcinoma and the relation between the two markers. 2-To assess the correlation between immunohistochemical expression of MMP-7 and CD34 with different clinicopathological variables. Patients, materials and methods: A retrospective study included the collection of 40 formalin –fixed paraffin- embedded gastric carcinoma tissue blocks (partial or total gasterectomy specimens) from the archived materials of the departments of pathology of the Gastrointestinal and liver disease teaching hospital, Al-Khadimiya teaching hospital, Teaching laboratories of the Medical city hospital, Al- Hussein teaching hospital in Karbala and a private laboratory covering the period from January to June 2010.
A five micrometers thick tissue sections were obtained from representative areas, one section was stained with hematoxylin and eosin and then reviewed, and two sections were stained immunohistochemically for MMP-7 and CD34. MMP-7 immunostaining in at least 30% of tumor cells cytoplasm and membranes was considered to regard the case as positive (over expression of MMP-7 ),CD34 immunostaining of endothelial cells was used to count the micro-blood vessels, and the hotspot method was used according to modified Wiedner's method, by choosing 3 hot spots with the most dense microvessel growth and calculating the microvessel density by dividing the mean microvessel count on the surface area of the 200x power field which equal 0.74mm2 . Results: A clinic-pathological assessment revealed that the age of patients was between 23-80 years with (a mean ± standard error of mean) of (53.50+2.05) year with the majority of gastric carcinoma cases 27 (67.5%) were equal or above fifty years, while 13(32.5%) of the cases were below 50 years. 27(67.5%) patients were males and 13(32.5%) cases were females with male to female ratio was 2.07:1. The majority of the studied cases were antral in location (27 case representing 67.5%) while the remaining cases distributed between pylorus, fundus, cardia or involving both antrum and fundus. The most common gross presentation was the ulcerative type (50%), followed by the polypoid type (32.5%). 65% of cases were equal or above 5 cm in maximum diameter while the remaining cases were below. Majority of cases (77%) were of intestinal type adenocarcinoma while the rest were of diffuse type gastric carcinoma .The poorly differentiated cases constituted 53% of the cases and the moderately differentiated tumors made the rest of the cases . the majority of cases fell into stage III with total number of 21 cases(52.5%), while 13 (32.5%) were of stage II, 4 cases (10%) were stage IV and 5% of cases were in stage IB .90% of cases had full invasion of stomach wall , 7.5% had subserosal invasion and 2.5% had full invasion with local invasion. Vast majority of the cases were with free resection margins (95%) while 5% had one involved surgical margin. Cases with lymph node involvement constituted 65%, while only 5% of the cases were with distant metastasis. The overall expression of MMP-7 in gastric carcinoma cases in the present study was (82.5%) of cases, while none of the studied adjacent non-cancerous mucosa showed positive expression. There was a statistically significant correlation between MMP-7 expression and the diffuse type of Lauren's classification of gastric carcinoma, also with pathological stage, and the depth of invasion. There was an inverse relationship between MMP-7 and age in years, and a higher expression in females than males but with statistically no significance (p<0.05), a higher expression was noted in those tumors involving both antrum and funds at the same time, and in those tumors with diffuse infiltrative pattern in addition in the poorly differentiated tumors than in the moderately differentiated one but also without statistical significance (p<0.05). There was a positive but statistically not significant correlation between MMP-7 expression and tumor size in centimeter, surgical margin involvement, lymph node invasion and metastatic status. A positive statistically significant relationship between the immunohistochemical expression of MMP-7 and CD34 was found. Mean MVD in the studied cases was (mean± standard error) of (122.12± 4.13). The only statistically significant correlation between MVD and the different clinic-pathological variables was with tumor stage, like MMP-7 expression mean MVD had an inverse relationship with age in years, and unlike MMP-7 it showed higher expression in males than in female but with no statistical significance. Again those tumors with antral and fundic involvement showed higher mean MVD than the rest of locations, also in the diffuse infiltrative gross pattern, and the poorly differentiated tumors above the moderately differentiated one, and the diffuse type gastric carcinoma than the intestinal type adenocarcinoma but all with no statistical significance. There was appositive but statistically not significant correlation between mean MVD and tumor size, increasing depth of invasion, margin involvement, advanced lymph node stage involvement and the metastatic status. Conclusion: The overall expression of MMP-7 in gastric carcinoma cases in the present study was (82.5%) of cases, and none of the adjacent non-cancerous mucosa showed positive expression. There was statistically positive correlation between MMP-7 expression and the diffuse type gastric carcinoma, TNM tumor stage and increasing depth of invasion, while mean MVD showed a statistically significant correlation only with TNM tumor stage . The relationship between immunohistochemical expression of MMP-7 expression and CD34 was also statistically significant.