Expression Of PTEN ,p27,Skp2 In Molecular Subtypes Of Breast Carcinoma And Relation In Basal-like Breast Carcinoma

Breast cancer is a heterogeneous disease that includes many morphological and molecular entities. Through the newly developed cDNA microarray and cluster analysis, based on difference of gene expression profile, breast cancer is categorized into five groups: luminal A [estrogen receptor (ER)+]; luminal B (ER+); basal-like ;HER2 over-expressing and normal breast-like. Based on molecular typing, basal-like breast carcinoma as a subtype of breast cancer has caused widespread concern. Basal-like breast carcinoma is considered as independent disease because of distinct gene expression, shorter survival, more conspicuous clinical and pathological feature. It has been investigative hot spot recently home and abroad. The PTEN tumor suppressor acts as a phosphatase for phosphatidylinositol-3,4,5-trisphosphate (PIP3). PTEN negatively controls the G1/S cell cycle transition and regulates the levels of p27 through PKB/Akt pathway.Skp2 acts as the specific substrate recognition subunit and binds p27 in a manner that depends on p27 phosphorylation and on the cofactor cyclin-dependent kinase -binding protein CKS1. It degradates p27 through ubiquitin- proteasome pathway to remove their inhibitory action to cyclin-CDK and cell cycle can progress. So the anomal expression and the cooperation of three genes play an important role in the developmen mechanism of the malignant tumor. The paper study the expression of PTEN,p27 and Skp2 in the molecular subtypes of breast carcinoma and analyses the effective and relationship in basal-like breast carcinoma.Materials and methods1. Materials: Test to collect 1452 invasive breast cancers.Patients who did not undertake chems and radiotherapy before the operation,have intact pathological datas.2. Methods: Immunohistochemistry was used to detect the expression of ER, PR, HER2, CK5/6 and EGFR on a tissue microarray containing 1452 cases of invasive breast carcinomas. Based on the results, the caseswere categorized according to Nielson criteria.Immunohistochemical MaxVision method was also used to detected the expression of PTEN,p27 and Skp2. The expression of mRNA of PTEN was detected by ISH(in situ hybridization).Results1. Of 428 cases, 56,223, 188 and 416 were classified as luminalA, luminalB, basal-like, HER2 over-expressing and null subtypes.2. Positive expression rates of PTEN protein in basal-like, HER2 over-expressing, null, luminal A and luminal B substypes were 38.9%,44.3%,30.5%,60.2% and 68.6%; the expression rates of p27 protein were 35.2%,46.3%,41.4%,55.9% and 63.0% and the expression rates of Skp2 protein were 63.3%,51.9%,53.1%,21.3%,13.7%. Like the phenotypes of basal-like, HER2 over-expressing and null, positive expression of PTEN and p27 protein were remarkably lower than luminal A subtype and luminal B subtype and positive expression of Skp2 were remarkably higher than luminal A subtype and luminal B (p<0.05). The expression of PTEN,p27 and Skp2 protein were associated with the expression of ER protein(p<0.01). In the basal-like breast cancer, there is significantly positive correlation between PTEN and p27,there is significantly negative correlation between p27 and Skp2,and there is significantly negative correlation between PTEN and Skp2(p<0.001).3. Positive expression rates of PTEN mRNA in basal-like, HER2 over-expressing, null, luminal A and luminal B substypes were 55.9%,67.0%,55.7%,85.0%,80.0%.Like the ER-negative breast cancer, positive expression of PTEN mRNA was remarkably lower than ER-positive(p<0.001). The expression of PTEN mRNA was associated with the expression of PTEN protein(p<0.001).Conclusions1.Like the ER-negative breast cancer, positive expression of PTEN protein was remarkably lower than ER-positive,so as the espression of PTEN mRNA. The down regulation expression of PTEN proteins in the ER-negative breast cancer may influence tumor's proceeding and growth importantly.2.The down regulation expression of PTEN proteins may play an important role in the ER-negative breast cancer. Further study of p27 will help to understand the ER-negative breast cancer occurrence and development mechanism, and may provide the basis for such a gene therapy to breast cancer.3.Like the ER-negative breast cancer, positive expression of Skp2 protein was remarkably higher than ER-positive.And like the basal-like breast cancer, positive expression of Skp2 protein was remarkably higher than others in ER-negative breast cancer. Skp2 in the basal-like breast cancer have a certain diagnostic value and it may be play an important role in the pathogenesis and the development of new therapeutic targets of basal-like breast cancer.4.The research of the relationship of three kinds of genes in the basal-like breast cancer may be supply the assistance for illuminating the nosogenesis.