Colo-rectal cancer tumor analysis (Microsatellite instability [MSI] testing, DNA mismatch repair [MMR] genetic testing, BRAF mutation analysis, Oncotype DX colon cancer assay)
المؤلف:
Kathleen Deska Pagana, Timothy J. Pagana, Theresa Noel Pagana.
المصدر:
Mosbys diagnostic and laboratory test reference
الجزء والصفحة:
15th edition , p262-263
2025-11-15
34
Type of test Microscopic examination
Normal findings
Recurrence score < 10
No mismatch repair gene
No microsatellite instability
Test explanation and related physiology
The prognosis of patients with colo-rectal cancer (CRC) is primarily determined by the stage of the cancer. However, within each stage, the recurrence rate varies considerably. Colo-rectal tumor analysis/genomic testing can help determine prognosis within these large variations. This information can also be helpful in determining if additional therapy is helpful after surgery. Tumor analysis is increasingly being used to indicate responsiveness to particular anti-cancer drugs. And finally, with the use of tumor molecular genetic analysis, genetic patterns can be determined and indicated whether a CRC is sporadic or familial (Lynch syndrome, etc.). This analysis is different than genetic testing for the identification of genetic alterations that cause familial CRC. Furthermore, this analysis is somewhat different than the information provided by genomic testing of the particular genes of CRC tumor as described on p. 457. Here, these genes and the proteins whose synthesis they direct are dis cussed separately.
Deficiencies in DNA mismatch repair (MMR) gene function (because of either decreased gene expression or mutation) result in the accumulation of DNA alterations that can mani fest as abnormal shortening or lengthening of microsatellite DNA sequences in the colon cancer cell. This causes micro satellite instability (MSI) and ultimately leads to the development of CRC. Patients with MMR-deficient (MMR-D) colon tumors have high MSI and have been shown to have significantly lower colon cancer recurrence risk. There are other MMR genes (MSH2, MSH6, and PMS2) that more rarely occur in CRC. Furthermore, hereditary colon cancers frequently are positive for MSI compared with sporadic colon cancers. Lynch syndrome (a hereditary form of colon cancer) can be suspected if the tumor is MSI positive.
Another important process in the development of CRC is chromosomal instability. APC, TP53, KRAS, and NRAS are some of the mutations that occur in this pathway. KRAS and NRAS may indicate responsiveness to anti-EGFR therapy.
BRAF is another important gene that is used to indicate the likelihood that a colon tumor is hereditary. The presence of a BRAF V600E mutation in a microsatellite unstable tumor indicates that the tumor is probably sporadic and not associated with hereditary nonpolyposis colorectal cancer (HNPCC).
BRAF is an important genetic mutation in other cancers such as melanoma, papillary thyroid cancer, hairy-cell leukemia, lung cancer, and other B-cell lymphomas. BRAF mutation may be associated with increased risk of recurrence, lymph node metastases, and advanced-stage cancer. Drugs that are BRAF inhibitors are specifically and successfully used on tumors that exhibit BRAF. Thus identifying BRAF mutations may be of critical therapeutic importance. BRAF p.V600 mutations have shorter progression-free survival and overall survival. Other possible predictor markers that can be identified on the tumor include PIK3CA and TP53.
Procedure and patient care
Before
* Inform the patient that an examination for these tumor predictor markers may be performed on their colon cancer tissue.
* Provide psychological and emotional support to the patients colon cancer.
During
• The surgeon obtains tumor tissue.
• This tissue should be placed on ice or in formalin.
• Part of the tissue is used for routine histology. A portion of the paraffin block is sent to a reference laboratory.
After
* Explain to the patient that results are usually available in 1 week.
Abnormal findings
- Unfavorable test results indicating a high risk of cancer reoccurrence
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