Summary & Overview
CPT 81288: MLH1 Promoter Methylation Analysis
CPT code 81288 denotes a molecular laboratory test for promoter methylation analysis of the MLH1 gene, a key assay in evaluating colorectal cancer etiology and Lynch syndrome–related findings. This test identifies epigenetic silencing of MLH1, which has implications for tumor classification, prognosis, and further genetic workup. Nationally, MLH1 methylation testing is important for precision oncology workflows and hereditary cancer evaluation pathways.
Key payers covered in this analysis include Aetna, Blue Cross Blue Shield, Cigna Health, UnitedHealthcare, and Medicare. Readers will find an overview of clinical context for the test, typical sites of service and billing considerations, and reference points for how major payers approach coverage and payment. The publication summarizes common billing modifiers and implementation elements relevant to laboratory technical services and highlights where data is available versus where input was not provided. Clinical implications of MLH1 promoter methylation testing and its role in diagnostic algorithms for colorectal cancer and mismatch repair deficiency are summarized to aid coding and administrative decisions.
This resource is intended for a national audience of coding professionals, laboratory directors, and health policy analysts seeking a concise reference on CPT code 81288 and its clinical and administrative context.
Billing Code Overview
CPT code 81288 describes a laboratory technical test that performs promoter methylation analysis of the MLH1 gene (mutL homolog 1), a gene associated with hereditary nonpolyposis colorectal cancer (Lynch syndrome) and sporadic colorectal tumors. The analysis detects epigenetic changes (promoter methylation) that can silence MLH1 expression, informing molecular characterization of colorectal and related cancers.
Service type: Molecular pathology / genetic laboratory test (technical component)
Typical site of service: Clinical laboratory or molecular diagnostics laboratory (hospital or independent lab)
Clinical & Coding Specifications
Clinical Context
A 52-year-old patient with a personal history of colorectal adenocarcinoma and concern for mismatch repair deficiency is referred for tumor testing. The pathology laboratory performs promoter methylation analysis of the MLH1 gene to evaluate for epigenetic silencing as part of Lynch syndrome workup and to distinguish sporadic MLH1 loss from germline mutation. The workflow: a surgical pathology specimen or formalin-fixed paraffin-embedded (FFPE) tissue block is accessioned; tumor enrichment and DNA extraction are performed by the molecular laboratory; the laboratory analyst runs the MLH1 promoter methylation assay (bisulfite conversion and methylation-specific PCR or alternative validated method); results are interpreted by molecular pathologist; a report is released to the ordering clinician. Typical site of service is an outpatient hospital laboratory or independent clinical molecular laboratory with specimens originating from oncology, gastroenterology, or surgical services. Common clinical indications include abnormal tumor immunohistochemistry showing loss of MLH1, evaluation of early-onset colorectal cancer, or family history suggestive of hereditary nonpolyposis colorectal cancer (Lynch syndrome).
Coding Specifications
| Modifier | Description | When to Use |
|---|---|---|
26 | Professional component | Use when billing only the physician interpretation/reporting portion separated from the technical lab work. |