| Objective:Compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS), invasive micropapillary carcinoma (IMPC) shows more distinctive morphologic characteristics and a biological feature with high incidence of axillary lymph node metastases. Proteomics technology can be used for high-throughput comparison of normal tissue and tumor tissue or different tumor protein expression profiles, showing the overall tumor protein expression profiling changes in tumor oncogenesis and development. Then find "tumor specificity molecular" to provide a new target for cancer diagnosis and its treatment. This study used comparative proteomics technology to find the differentially expressed proteins between IMPC and IDC-NOS, followed by verification. Afterward, the mechanisms of biological behavior with high incidence of axillary lymph node metastases of IMPC were explored from the point view of proteomics.Methods:Candidate molecules were obtained by examining the differential expression spots in three groups of IMPC and IDC-NOS frozen tissues. Two-dimensional polyacrylamide gel electrophoresis was obtained and dyed with silver salt, undergone ImageScanner scanning and transformed into digital image. Then we chose protein spots with better repeatability and resolution to be identified by mass spectrometry. The immunohistochemical stain assay was used to verify the expression of these candidate molecules in the Paraffin tissue sections of43IMPC and30IDC-NOS samples and analyzing the relationship between the expression of Hsp27and the various pathologic parameters of invasive micropapillary carcinoma.Results:1、In three groups of breast IMPC and IDC-NOS frozen tissues after undergoing two-dimensional electrophoresis, we screened out65,66and27protein spots with stable expression differences respectively.2、One differentially expressed protein, namely, Heat shock protein27(Hsp27) was screened out after mass spectrum. 3、The expression of Hsp27was up-regulated of5.114times in IMPC compared with that in IDC-NOS by PDQuest software protein spots retrospective analysis tools.4、According to the percentage of IMPC component in the whole tumor, we divided IMPC into different groups, and then analyzed the relationship among the percentage of IMPC, the expression of Hsp27and the extent of lymph node metastasis. The percentage of IMPC component in the whole tumor was not significantly associated with the expression of Hsp27(P=0.563) and the extent of lymph node metastasis (P=0.088).5、Hsp27was mainly expressed in the plasma of tumor cells, fewer in the nucleus. Hsp27expressed positively97.67%(42/43) in breast IMPC, significantly higher than IDC-NOS group86.66%(26/30), and the main expression was++(46.5%) and+++(25.6%) in IMPC comparing with IDC-NOS group by+(53.3%) mainly (Z=-3.236, P=0.001).6、The expression of Hsp27positively correlated with the ER (r=0.319, P=0.037) and metastasis in lymph nodes (r=0.444, P=0.003). No correlation was found between Hsp27and the patients age, pathologic stage, and PR or HER-2. No correlation was found between Hsp27and metastasis in lymph nodes in IDC-NOS (P>0.05).Conclusions:1、Hsp27over-expressed in IMPC compared with IDC-NOS.2、The expression of Hsp27was positively correlated with the extent of lymph node metastasis in IMPC but with no correlation in IDC-NOS indicating that Hsp27may play an important role in lymph nodes metastasis of IMPC.3、The expression of Hsp27in IMPC was positively correlated with the expression of ER, combined with previous studies, suggesting that for ER+Hsp27+breast cancer patients, endocrine united Hsp27silence therapy may be able to enhance the therapeutic effect of endocrine. |
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