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50 gene signature (PAM50)

The 50 gene signature most commonly refers to the PAM50 gene signature, which is a genomic assay used in breast cancer to classify tumors into intrinsic molecular subtypes and to provide prognostic information.

The Prediction Analysis of Microarray 50 (PAM50) gene signature assay (Prosigna) uses the nCounter (NanoString Technologies) platform to measure the expression of 50 genes in breast cancer, categorizing tumors into 4 molecular subtypes: luminal A, luminal B, ERBB2− enriched, and basal-like.

The PAM50 assay generates a risk of recurrence (ROR) score, which is used to estimate the probability of distant recurrence over 10 years, particularly in hormone receptor–positive, early-stage breast cancer.

The PAM50 signature is distinct from other gene expression assays (such as the 21-gene Oncotype DX or the 70-gene MammaPrint) in that it focuses on intrinsic subtyping and its validated prognostic utility in diverse populations.

The test is performed on formalin-fixed, paraffin-embedded tissue.

It is a used in clinical practice to guide adjuvant therapy decisions in early-stage breast cancer.

50 genes plus 8 reference genes selected to optimize the accuracy of identifying the four major breast cancer subtypes.

Multi-gene prognostic tests by mRNA expression of 50 genes (PAM50) have been shown to improve prognostication significantly compared to standard tumor characteristics and other genomic signatures: the prognostic value of PAM50 intrinsic subtype was greater than estrogen receptor/HER2 immunohistochemistry classification.

The PAM50 signature is particularly valuable for hormone receptor-positive breast cancer patients.

 

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