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Abstract Background Experimental evidence suggests that matrix metalloproteinase-13 (MMP-13) protein may promote breast tumor progression, however, its role is yet to be fully established. Furthermore, it is not clear whether MMP-13 can be used as an independent breast cancer biomarker. This study was conducted to assess the expression profile of MMP-13 protein in invasive breast carcinomas to determine its diagnostic and prognostic significance, as well as its correlation with other biomarkers including estrogen receptor (ER), progesterone receptor (PR), Her-2/neu, MMP-2, MMP-9, tissue inhibitor of MMP-1 and -2 (TIMP-1 and TIMP-2). Methods Immunohistochemistry (IHC) was performed on paraffin-embedded tissue microarray specimens from 263 breast carcinomas. The intensity and the extent of IHC were scored by pathologists. The correlation of the gene expression profiles with the patients' clinicopathological features and clinical outcomes were analyzed for statistical significance. Results MMP-13 protein was detected in the cytoplasm of malignant cells and peritumoral stromal cells. MMP-13 expression by tumor cells (p < 0.001) and stromal fibroblasts (p < 0.001) both correlated with carcinoma infiltration of lymph nodes. MMP-13 also correlated with the expression of Her-2/neu (p = 0.015) and TIMP-1 (p < 0.010), respectively in tumor cells. Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes. Moreover, high levels of MMP-13 expression were associated with decreased overall survival. In parallel, the prognostic value of MMP-13 expressed by peritumoral fibroblasts seems less significant. Our data suggest that lymph node status, tumor size, Her-2/neu expression, TIMP-1 and MMP-13 expression in cancer cells are independent prognostic factors. Conclusion Tumor-derived, but not stromal fibroblast-derived, MMP-13 correlated with aggressive tumor phenotypes, and inversely correlated with overall survival of breast cancer patients. MMP-13 may serve as an independent prognostic factor for invasive breast cancer patients. MMP-13 may be particularly useful as a prognostic marker when evaluated along with Her-2/neu and lymph node status.

Background: The application of circulating, cell-free, methylated Septin9 (mSEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of mSEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring.Methods: For screening and diagnosis of CRC, peripheral mSEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of mSEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT).Results: Seventy-three percent of CRC patients were mSEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were mSEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of mSEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of mSEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of mSEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR).Conclusions: mSEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of mSEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR. [ABSTRACT FROM AUTHOR]

Background: The application of circulating, cell-free, methylated Septin9 ( m SEPT9) DNA in screening and recurrence monitoring is highly promising. CpG island methylator phenotype (CIMP) is associated with microsatellite instability (MSI). The present study was performed to determine the diagnostic accuracy of m SEPT9 for colorectal cancer (CRC) and to evaluate its utility in CRC screening and recurrence monitoring., Methods: For screening and diagnosis of CRC, peripheral m SEPT9 detection and fecal occult blood test (FOBT) were performed in 650 subjects, then the level of CEA, CA19-9 and CA724 was quantified in 173 subjects. Clinicopathological parameters and mismatch repair protein were detected among subjects with CRC. For recurrence monitoring of CRC, the sensitivity of m SEPT9 of 70 subjects was compared with tumor markers and contrast enhanced computed tomography (CECT)., Results: Seventy-three percent of CRC patients were m SEPT9-positive at 94.5% specificity, and 17.1% of patients with intestinal polyps and adenoma were m SEPT9-positive at 94.5% specificity, which were higher than FOBT for the screening of CRC. The sensitivity and specificity of m SEPT9 for diagnosis and recurrence monitoring were higher than that of CEA, CA19-9 and CA724. The combined detection of m SEPT9 and CECT enhanced the sensitivity for recurrence monitoring. Pre-therapeutic levels of m SEPT9 were strongly associated with TNM stage, Dukes stages and mismatch repair deficiency (dMMR)., Conclusions: m SEPT9 analysis might be popularized as a routine biomarker for CRC screening. The combined detection of m SEPT9 and CECT can play an important role for recurrence monitoring. CIMP was highly associated with the pathological stage of CRC and dMMR.