title: Motility-related protein-1 (MRP-1/CD9) reduction as a factor of poor prognosis in breast cancer.
abstract: The application of reliable markers is of major importance for predicting the prognosis of and instituting the appropriate postsurgical treatment of patients with breast cancer. Previously we showed that motility-related protein-1 (MRP-1), which is identical to CD9, regulates cell motility, and that cultured tumor cells transfected with MRP-1/CD9 cDNA have low motility and low metastatic potential. In addition, MRP-1/CD9 immunoblotting and immunohistochemical study with breast cancer revealed that MRP-1/CD9 expression diminished as the clinical stage of a given breast cancer advanced and that the MRP-1/CD9 gene and protein expression in the metastatic lymph nodes was strikingly lower than in the primary breast cancers. In this study, we also investigated the expression of MRP-1/CD9 by immunoblotting and immunohistochemical analysis in 143 freshly resected invasive ductal carcinomas of the breast: 52 tumors were stage I, 61 were stage II, and 30 were stage III. Tumors were classified as MRP-1/CD9 positive when a band intensity of >30% compared with positive control cells, ZR-75-30 were evaluated with the antibody M31-15, and those with intensities <30% as negative. Moreover, these results were ascertained by immunostaining. Tumor specimens classified as MRP-1/CD9 positive using Western blotting had >50% of the cancer cells immunostained with M31-15, and those classified as MRP-1/CD9 reduced had <50% of the cancer cells immunostained with M31-15. There were 97 patients with MRP-1/CD9 positive tumors and 46 patients whose tumors had reduced MRP-1/CD9 levels. The disease-free rate of the former group of patients was strikingly higher than that of the latter (84.7% versus 51.4%, P<0.001). Similarly, the overall survival rate was also significantly different between the two groups (93.6% versus 69.6%, P=0.004). Multivariate analysis with the Cox regression model indicated that MRP-1/CD9 positively correlated better with disease-free survival (P<0.001) than estrogen receptor, tumor, and lymph node status. Our data suggest that low MRP-1/CD9 expression by tumors of the breast may be associated with poor prognosis. It is conceivable that testing for MRP-1/CD9 may identify node-negative breast cancer patients who are at high risk for early disease recurrence.
authors.affiliation: Department of Thoracic Surgery, Kitano Hospital, Osaka, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyake
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: S I
authors.initials: SI
authors.lastname: Itoi
authors.forename: T
authors.initials: T
authors.lastname: Koh
authors.forename: T
authors.initials: T
authors.lastname: Taki
mesh_terms: D015703:Antigens, CD / Q000032:analysis* / Q000737:chemistry; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000737:chemistry; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis* / Q000737:chemistry; D009367:Neoplasm Staging; D011379:Prognosis; D011446:Prospective Studies; D060245:Tetraspanin 29
chemical_list: D015703:Antigens, CD; C554869:CD9 protein, human; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D060245:Tetraspanin 29