New Insight Into The Progression And Invasiveness Of The Most Common Type Of Breast CancerMain Category: Breast Cancer
Also Included In: Cancer / Oncology
Article Date: 17 Oct 2012
Ductal carcinoma in situ (DCIS) can be a predictor for invasive breast cancer if untreated, and is seen in around 45 percent of patients with invasive ductal carcinoma (IDC). Patients who only have DCIS, have a 5-year-survival of almost 100 percent on contrast to 89 percent of all stages of invasive breast cancer.
This new study suggests that regardless of a large amount of intercellular heterogeneity in both IDC and DCIS, the transformation from noninvasive to invasive disease is decided by repeating patterns of genomic variances in most cases.
Lead investigator Thomas Ried, Section Chief, Genetics Branch, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, says:
"For patients with cancer, the transition from locally controlled disease to a disseminated stage and metastases is probably the most critical threshold, because that transition makes surgical intervention considerably less likely to succeed. We looked at gene copy number changes during the transition from DCIS to IDC and, if so, what patterns of genetic imbalances drive this process."
The study, published in The American Journal of Pathology, examines old clinical samples that contained patients who had DCIS and IDC, and had been tracked at the National Naval Medical Center.
The researchers compared the genetic makeup of single cells from 13 patients with both DCIS and IDC, and assessed the gain or loss of certain genes that are commonly affected in DCIS and IDC. Genes that were assessed included cancer promoting oncogenes and cancer suppressing tumor suppressor genes.
Fluorescence in situ hybridization (FISH) probe panels, that use fluorescent clones of the participating DNA sections to recognize gene copy numbers, were hybridized into complete cells, prepared from histomorphologically identified ares from the lesions of many patients.
Succeeding hybridizations of multicolor probe panels caused multiplexing of problems that then authorized for synchronized analysis of copy numbers of give oncogenes and three tumor suppressor genes within each cell examined.
Observations revealed a high rate of chromosomal instability from one cell to another, shown by the fact that alike signal clones were just present in less than 20 percent of the cells.
Even with this variability, the spread of gains and losses in the majority of cases was constant with known genetic abnormality profiles for breast cancer. Investigators found designs consistent with systematic distribution of genomic imbalances.
CDH1, a tumor suppressor that prompts cancer invasion and metastases at the pint of reduced expression, was frequently missing in DCIS and IDC. MYC, a strong oncogene that pushes cell proliferation and controls cell growth and differentiation, was seen to be gained from DCIS to IDC. MYC plays a critical part in the transition from "in situ" to invasive breast cancer.
Dr. Ried explains:
"DCIS and IDCs are genetically related lesions as they both have similar imbalance patterns. However, according to their aberration patterns, the DCIS lesions are far further advanced than other precursor lesions with more stable genomes, such as colorectal polyps or cervical dysplasias. The considerable degree of intercellular heterogeneity in the DCIS convincingly attests to the fact that chromosomal instability precedes the transition to invasive disease."
The conclusion that the advanced abnormality profiles of DCIS linked with IDC, suggest that it is doubtful that transition to invasive disease can be prevented with actions other than radiation, surgery, and adjuvant hormonal therapy.
The authors go on to say that future studies will need to be done to see what decides this important transition between pre-invasive and invasive disease. By examining the full catalog of genes in DCIS and IDC, and identifying the differences, there could be a gene expression discovered that could be accountable for invasion and progression.
Written by Kelly Fitzgerald
Copyright: MediLexicon International Ltd
Original article posted on Medical News Today.
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