Novel immunohistochemistry-based signatures to predict metastatic site of triple-negative breast cancers.

BACKGROUND: Although distant metastasis (DM) in breast cancer (BC) is the most lethal form of recurrence and the most common underlying cause of cancer related deaths, the outcome following the development of DM is related to the site of metastasis. Triple negative BC (TNBC) is an aggressive form of BC characterised by early recurrences and high mortality. Athough multiple variables can be used to predict the risk of metastasis, few markers can predict the specific site of metastasis. This study aimed at identifying a biomarker signature to predict particular sites of DM in TNBC. METHODS: A clinically annotated series of 322 TNBC were immunohistochemically stained with 133 biomarkers relevant to BC, to develop multibiomarker models for predicting metastasis to the bone, liver, lung and brain. Patients who experienced metastasis to each site were compared with those who did not, by gradually filtering the biomarker set via a two-tailed t-test and Cox univariate analyses. Biomarker combinations were finally ranked based on statistical significance, and evaluated in multivariable analyses. RESULTS: Our final models were able to stratify TNBC patients into high risk groups that showed over 5, 6, 7 and 8 times higher risk of developing metastasis to the bone, liver, lung and brain, respectively, than low-risk subgroups. These models for predicting site-specific metastasis retained significance following adjustment for tumour size, patient age and chemotherapy status. CONCLUSIONS: Our novel IHC-based biomarkers signatures, when assessed in primary TNBC tumours, enable prediction of specific sites of metastasis, and potentially unravel biomarkers previously unknown in site tropism.

The more the messier: centrosome amplification as a novel biomarker for personalized treatment of colorectal cancers.

Colon cancer is currently the third most common cancer and second most fatal cancer in the United States, resulting in approximately 600,000 deaths annually. Though colorectal cancer death rates are decreasing by about 3% every year, disease outcomes could be substantially improved with more research into the drivers of colon carcinogenesis, the determinants of aggressiveness in colorectal cancer and the identification of biomarkers that could enable choice of more optimal treatments. Colon carcinogenesis is notably a slow process that can take decades. Known factors that contribute to the development of colon cancer are mutational, epigenetic and environmental, and risk factors include age, history of polyps and family history of colon cancer. Colorectal cancers exhibit heterogeneity in their features and are often characterized by the presence of chromosomal instability, microscopic satellite instability, or CpG island methylator phenotype. In this review, we propose that centrosome amplification may be a widespread occurrence in colorectal cancers and could potently influence tumor biology. Moreover, the quantitation of this cancer-specific anomaly could offer valuable prognostic information and pave the way for further customization of treatment based on the organellar profile of patients. Patient stratification models that take into account centrosomal status could thus potentially reduce adverse side effects and result in improved outcomes for colorectal cancer patients.