LAG3 IHC Melanoma

Formalin fixed paraffin-embedded (FFPE) tissue

Paraffin block or 5 unstained slides

Paraffin block or 5 unstained slides

Paraffin block or slide

The LAG3 assay is intended for use in the detection of LAG3 in formalin-fixed, paraffin-embedded (FFPE) tissue sections in melanoma.

Use of fixatives other than 10% formalin may not yield equivalent or satisfactory results.

This test was developed and its performance characteristics determined by Labcorp. It has not been cleared or approved by the Food and Drug Administration.

The LAG3 Immunohistochemistry Assay uses a mouse monoclonal anti-LAG3 antibody (clone 17B4) with the Leica Bond Polymer Refine Detection kit on Leica Bond III automated staining platform. LAG3 expression is assessed as the percentage of immune cells with positive staining that had a morphologic resemblance to lymphocytes within the tumor region (consisting of the tumor, intervening stroma, and invasive margin) relative to all nucleated cells in the tumor region in samples containing at least 100 viable tumor cells. A > or = to 1% cutoff is used to determine LAG-3 positivity.

Lymphocyte-activation gene 3 (LAG3) is an immune checkpoint receptor protein expressed on the cell surface of multiple immune cell types including effector T cells, regulatory T cells (Tregs), NK cells, B cells, and plasmacytoid dendritic cells. When engaged, LAG3 functions by delivering inhibitory signals that regulate immune cell homeostasis, T cell activation, proliferation, cytokine production, and cytolytic activity. Preclinical studies suggest that inhibiting LAG3 allows T cells to regain their cytotoxic function and potentially affect tumor growth. LAG3 expression is also being evaluated as a biomarker to predict response to treatment. Early research suggests that targeting the LAG3 pathway in combination with other potentially complementary immune pathways may be a key strategy to more effectively activate the antitumor immune response. In advanced melanoma, inhibition of LAG3 and PD-L1 provided improved progression-free survival than inhibition of PD-1 alone. While a >1% cutoff for LAG3 positivity is used for this test, there was also a benefit of the combination therapy in patients with <1% LAG3.