CPT® Code 81288

MLH1 (mutL homolog 1, colon cancer, nonpolyposis type 2) (eg, hereditary non-polyposis colorectal cancer, Lynch syndrome) gene analysis; promoter methylation analysis

The CPT® Code 81288 refers to a specific laboratory test that analyzes the MLH1 gene, which is crucial in understanding certain types of colorectal cancer, particularly hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome. This genetic condition is inherited in an autosomal dominant manner, meaning that a mutation in just one copy of the gene can increase an individual's risk of developing various cancers, especially in the colon and rectum, as well as benign polyps. The MLH1 gene, located on chromosome 3, plays a vital role in the DNA mismatch repair system. When mutations occur in this gene, the body's ability to correct errors that arise during DNA replication is compromised, leading to an increased likelihood of tumor formation. The test is specifically performed on tumor tissue when the detection of a BRAF codon 600 mutation is negative. This distinction is important as it helps differentiate between tumors associated with Lynch syndrome and those that are sporadic, which may also exhibit loss of the MLH1 gene. The process involves obtaining tumor tissue through a surgical or biopsy procedure, which must be reported separately. Once the sample is collected, it is fixed in paraffin and subjected to qualitative real-time polymerase chain reaction (PCR) for promoter methylation analysis. This method allows for the detection of methylation changes in the promoter region of the MLH1 gene, which can indicate whether the gene is silenced in the tumor, further aiding in the diagnosis and management of colorectal cancer associated with Lynch syndrome.