Correlation of Immunohistochemical expression of MMP-3 and MMP-8 with Lymphovascular Permeation in Breast Carcinoma (A Clinicopathological Study)

Breast carcinoma is the most common malignant tumor and the leading cause of carcinoma death in women, with more than 1,000,000 cases occurring worldwide annually. Matrix Metalloprotienases are a family of more than 17 human zinc-dependant endopeptidases collectively capable of degrading essentially all ECM components, so they have a role in tumor growth, invasion and metastasis. Stromelysin-1(MMP-3) has a broad substrate specificity and can degrade proteoglycans and glycoprotiens such as laminin and fibronectin. The expression of MMP-3 in breast carcinoma cells enhances their invasion. Neutrophil collaginase(MMP-8)can degrade interstitial collagen(type I,II,III).The expression of MMP-8 in breast carcinoma cells inhibits their ability to spread.The Aim of the Study: 1.To evaluate the expression of MMP-3 and MMP-8 in breast carcinoma immunohistochemically and to correlate this expression with lymphovascular invasion by malignant cells, using CD34 to highlight the endothelial cells.2.To correlate the immunohistochemical expression of MMP-3 and MMP-8 with patient’s age, tumor grade, stage, L.N status and lymphovascular invasion. Patients, Materials and Methods: A retrospective study included the collection of 64 formalin fixed, paraffin embedded tissue blocks from archived material at Al_Kadimiya Teaching Hospital (covering the period from January to November 2010), and Teaching Laboratories of the Medical City Center(covering the period from January to October 2009).62 blocks represent the mastectomy specimens of breast carcinoma cases and 2 blocks represent benign breast lesions(one is benign phylloides tumor and the other is ductal hyperplasia). Four sections of 5µm thickness were taken from each block, the first was stained by hematoxylin and eosin stain (H&E) for histopathological revision, the remaining three sections were stained immunohistochemically for MMP-3 , MMP-8 , and CD34 respectively.
Results:The age of patients was between 30_70 years with a mean of (48.55+/_1.3 year), the majority of cases(45.2%)were in the age interval 50_59 years and the lowest percentage(16.1%) were in age 60 years and above. Sixty-four and a half present of cases were Grade II , 25.8% Grade III and 9.7%(the lowest percentage) were Grade I breast carcinoma. The majority of the studied cases (74.2%) were Invasive ductal carcinoma not otherwise specified. Forty four cases(70.96%) were associated with lymph node involvement by metastatic tumor cells and 18 cases(29.03%) were negative lymph nodes. Forty six cases were associated with lymphovascular permeation and 16 cases(25.8%) were not associated with lymphovascular permeation. There was a statistically significant correlation between lymphovascular permeation and lymph node(s) involvement(P<0.001) with an Odd ratio of 23(95% CI).Thirty tow cases(51.6%) were with T2 tumor size, 18 cases(29%) were with T3, and 12 cases(19.4%) were T1.In the present study the overall expression of MMP-3 in breast carcinoma cases was in 56 cases (90.31%), while MMP-8 was positively expressed in 18 cases(29.03%). There was a statistically significant correlation between MMP-3 expression and age of the patients, tumor grade, tumor size, histological subtype, lymph node involvement , and lymphovascular permeation. Strong expression for MMP-3 was noticed in high grade tumors, large size tumors, cases associated with positive lymph nodes and lymphovascular permeation(positive correlation). There was a statistically significant correlation between MMP-8 expression and tumor size, grade , histological subtype, lymph node involvement, and lymphovascular permeation, while there was no statistically significant correlation between MMP-8 expression and age of the patients (P= 0.072) .Negative expression for MMP-8 was noticed in most of the cases associated with lymphovascular permeation and positive lymph node(s) involvement by the metastatic cells (inverse relationship). Also a negative expression for MMP-8 was noticed in most cases associated with high grade, large size tumors. Conclusions: MMP-3 was positively expressed in 90.31% of cases of breast carcinoma, while MMP-8 was positively expressed in 29.03% of cases. There was a statistically positive correlation between MMP-3 expression and tumor size , grade , lymph node(s) involvement and lymphovascular permeation ,while a negative correlation was noticed between MMP-8 expression and the above mentioned parameters.