Expression And Clinical Significance Of ADAM10in Breast Cancer

Objective: The disintegrin metalloproteases (ADAMs) is a family of typeⅠtransmembrane proteins, also called metalloproteinase disintegrin or MDC(metalloprotease/disintegrin/cysteinerich), which plays a vital role in theregulation of cell-cell and cell-matrix interactions. Different members ofADAMs have been detected from cells, transgenic animals and otherexperimental systems in recent years around the world, and now the number isbeyond40. What matters is that ADAMs is playing an important role in theinvasion and metastasis of malignancy. To investigate the role of ADAM10inthe invasion of breast cancer and the relationship between ADAM10andE-cadherin, C-erbB-2, clinicopathological parameters (including menstrualstatus, tumor size, histological grade in invasive ductal carcinoma, clinicalstage, lymph node metastasis), We detect the expression of protein ADAM10,in non-tumor tissue of breast，breast cancer and lymph nodes metastases withIHC, hoping if we can forecast its possibility to become a invasive molecularmarker of breast cancer, and provide a new target for clinical treatment andexperimental basis.Methods:1Sixty specimens of paraffin-embedded human breast cancer tissues,twenty-two specimens of metastatic lymph nodes are obtained as experimentalgroup and twenty specimens of non-tumor tissues of breast as comparison. Allthe cases didn’t accept chemotherapy, radiotherapy, endocrine therapy andbiotherapy or other treatment before modified radical mastectomy.2Immunohistochemical technique (IHC, SP means) is applied to detectthe expression of ADAM10in non-tumor tissue of breast, breast cancer tissuesand lymph nodes metastases, and the expression of E-cadherin and C-erbB-2in breast cancer tissues. 3Statistical analysis: Pearson Chi-square (χ~2) test or Fisher exact test, ttest or t’ test, Rank convert non-parametric test and Spearman’s rankcorrelation analysis were performed with software SPSS13.0. The probability(P)-value less than0.05was considered to be statistically significant.Result:1Expression of protein ADAM10.1.1Expression of protein ADAM10in non-tumor tissue of breast，breastcancer and lymph nodes metastases.With IHC, the expression of ADAM10in non-tumor tissue of breast could bedetected with the staining intensity of brownish yellow. But there were a largenumber of positive cells in breast cancer tissues, staining intensities mostlybrownish yellow or tan. Lymph nodes metastases of breast cancer alsopresented amounts of positive cells; staining intensities mostly were brownishyellow or brown. The expression of ADAM10in breast cancer tissues wasremarkably higher than non-tumor tissue of breast,83.3%(50/60) and55.0%(11/20) respectively,(χ~2=6.649, P=0.015), but there was no significantdifference between breast cancer and lymph nodes metastases,83.3%(50/60)and77.3%(17/22) respectively,(χ~2=0.396,P=0.369), and no correlation (rs=-0.131,P=0.323) in22breast cancer tissues and their lymph nodemetastases.1.2Relationship between ADAM10and clinic pathological parameters ofbreast cancer.In this experiment, the expression of ADAM10were divided into lowexpression (including negative, weakly positive, positive) and high expression(strongly positive) when carried out the statistical analysis of the relationshipbetween ADAM10in breast cancer and clinic pathological parameters, forADAM10expression existed in both non-tumor tissue of breast and breastcancer. The rates of high expression of ADAM10were63.0%(17/27),42.4%(14/33) respectively in premenopausal and postmenopausal patients, thedifference was not statistically significant (χ~2=2.509, P=0.129).The highexpression of ADAM10in the group which the length of tumor≤2cm was positive rates were34.6%(9/26) and64.7%(22/34) respectively,(χ~2=5.342,P=0.036). In invasive ductal carcinoma, the high expression of ADAM10inhistological grade Ⅲ group was higher than that in the histological grade Ⅰ~Ⅱ group, the positive rates were83.3%(10/12) and43.3%(13/30)respectively, the difference was statistically significant (χ~2=5.536, P=0.037).The high expression of ADAM10in the group of stage Ⅰwas lower than thatin the group of stageⅡ~Ⅲ, the positive rates were22.2%(4/18),64.3%(27/42) respectively,(χ~2=8.927, P=0.004). The high expression of ADAM10in the group of lymph node metastasis group was significantly higher than thatin the group of lymph node non-metastasis, the positive rates were69.2%(18/26),38.2%(13/34) respectively,(χ~2=5.668,P=0.021).2Expression of E-cadherin and C-erbB-2in breast cancer tissues.E-cadherin protein in breast cancer was mainly expressed in the cellmembrane, and the staining intensitise of positive cells were light brown to tanwith the positive rate of91.7%(55/60). C-erbB-2protein in breast cancer wasmainly expressed in the cell membrane, and the positive cells appearedcontinuous brown particles in the cell membrane with the positive rate of41.7%(25/60).3Correlation ship between the expression of ADAM10and E-cadherin inbreast cancer tissues.In the60cases of breast cancer, there were27cases which wereE-cadherin-positive/ADAM10high-express,4cases that E-cadherin-negative/ADAM10high-express,28cases that E-cadherin-positive/ADAM10low-express,1cases that E-cadherin-negative/ADAM10low-express. Theresults of E-cadherin and ADAM10was analyzed by spearman rankcorrelation analysis，and showed no significant correlation (rs=-0.221, P=0.317). The differences have no statistically significant (χ~2=1.753, P=0.355)，although the ADAM10high-express rate (80%,4/5) of the group ofE-cadherin-negative was higher than the group of E-cadherin-positive (49.1%,27/55). 4Correlation ship between the expression of ADAM10and C-erbB-2in breastcancer tissues.In the60cases of breast cancer, there were16cases which wereC-erbB-2-positive/ADAM10high-express,15cases that C-erbB-2-negative/ADAM10high-express,9cases that C-erbB-2-positive/ADAM10low-express,20cases that C-erbB-2-negative/ADAM10low-express. Theresults of C-erbB-2and ADAM10was analyzed by spearman rank correlationanalysis，and showed no significant correlation (rs=0.163, P=0.215). Thedifferences have no statistically significant (χ~2=2.611, P=0.124)，althoughthe ADAM10high-express rate (64.0%,16/25) of the group ofC-erbB-2-positive was higher than the group of C-erbB-2-negative (42.9%,15/35).5The relationship among ADAM10,E-cadherin and the length of tumor,lymph node metastasis.Based on the results of immunohistochemical staining of ADAM10andE-cadherin, the60cases of breast cancer were divided into two groups,ADAM10high expression/E-cadherin-positive group as group1, ADAM10low expression/E-cadherin-positive, ADAM10high expression/E-cadherin-negative, ADAM10low expression/E-cadherin-negative as group2. The length of tumor of group1[2.567(1.00) cm] was longer than group2[2.0(1.65) cm],(Z=-2.013, P=0.022), lymph node metastasis rate in group1(59.3%,16/27) was higher than group2(30.3%,10/33)(χ~2=5.071,P=0.023).6The relationship among ADAM10,C-erbB-2and the length of tumor, lymphnode metastasis.Based on the results of immunohistochemical staining of ADAM10andC-erbB-2, the60cases of breast cancer were divided into two groups,ADAM10high expression/C-erbB-2-positive group as group1, ADAM10low expression/C-erbB-2-positive, ADAM10high expression/C-erbB-2-negative, ADAM10low expression/C-erbB-2-negative as group2.The length of tumor in group1(2.300±0.606cm) and group2(2.377±1.036cm)had no significant difference,(t=0.214, P=0.831); lymph node metastasis rate in group1(66.7%,6/9) was higher than group2(39.2%,20/51) with nostatistical significance (χ~2=2.348, P=0.157).Conclusion:1ADAM10might play an important role in the invasion and metastasisof breast cancer.2There was no correlation between the expression of ADAM10in breastcancer and lymph node metastases.3There might exist some synergistic effect between ADAM10andE-cadherin to promote local invasion and metastasis of breast cancer.4ADAM10and C-erbB-2did not appear significant synergistic effect inthe invasion and metastasis of breast cancer cells.