| Objective:To investigate the expression of MTDH in intraductal proliferative lesions, including usual ductal hyperplasia (UDH), atypical ductal hyperplasia(ADH) and ductal carcinoma in situ(DCIS) of breast, as well as invasive breast carcinoma. At the same time we analyzed the SNPs of MTDH in order to know what role the MTDH plays in the breast cancer.Methods:The MTDH expression was analyzed in 80 intraductal proliferative lesions, 162 invasive breast cancer tissues and 7 normal tissues by immunohistochemistry SP three-step method. Genomic DNA extracted from blood samples of 65 breast cancer patients and 60 health persons, amplified by polymerase chain reaction(PCR) and sequenced to find the new single nucleotide polymorphisms. Analyses were performed using the statistical software package SPSS 13.0 (SPSS, Chicago, IL).Results:1. Using immunohistochemistry method, in the proliferative lesions, high expression of MTDH protein was found in 7/29(24.14%) cases of UDH,4/14(28.57%) cases of ADH and 27/37(72.97%) cases of DCIS. But in the normal tissues, no high expression of MTDH was found. Compared with them, elevated MTDH protein expression was detected in 90/162(55.56%) cases of invasive breast carcinoma. The expression difference of them was significant tested by linear-by-linear association (P< 0.001). 2. Statistical analyses indicated that the correlation between MTDH and Ki67 expression was significant (P= 0.008) in DCIS. In the high grade DCIS, the rate of high expression of MTDH is 93.3%, and in the low grade DCIS, the rate of high expression of MTDH is 59.09%, the difference between them was significant(P= 0.028).3. In invasive breast cancer, MTDH expression strongly correlated with the patients' age (P= 0.042), Ki67 status (P= 0.036), ER status (P= 0.018) and p53 status (P= 0.001).4. We found several SNPs of MTDH in 5'upsteam and 3'UTR of Extron 12, including-470G>A,-200G>A,2928C＞T,3088A>G and 3540T>C. Three SNPs (2928C＞T,3088A>G,3540T>C) which located at 3'UTR of Extron 12 are complete linkage disequilibrium, D'=1, r2=1. We found two haplotypes, C2928A3088T3540 and T2928G3088C3540 .5. Between the breast carcinoma group and control group, there was no significant difference in the distribution of the three genotypes and the frequencies of the two alleles at these five SNPs(P>0.05).Conclusion:1. MTDH is not overexpressed in normal breast tissue, but with the intraductal proliferative lesions progression, the expression level and intensity are higher and stronger gradually. MTDH might play a role in the development and progression of breast proliferative lesions. The rate of high expressed MTDH in DCIS is higher than that in invasive ductal carcinoma. This may suggest that MTDH plays a more important role in initiation of breast carcinoma.2. MTDH is overexpressed in highly proliferative lesions of breast cancer and DCIS. It suggests that increased cell proliferation associate with overexpressed MDTH.3. The expression rate and intensity of MTDH in UDH, ADH, DCIS are difference. In DCIS, especially in high grade DCIS, the rate of high expression of MTDH is higher than that in ADH and UDH. This might suggest that MTDH plays an important role in the process of breast oncogenesis.4. In breast cancer, the overexpression of MTDH is associated with high p53 expression, younger patient and negative estrogen receptor status. This indicates MTDH may be a poor prognostic factor.5. Five new SNPs of MTDH are found, but no one is associated with the susceptibility of breast cancer. |
