Multisite Validation Study To Determine Performance Characteristics of a 92-gene Molecular Cancer Classifier.

Kerr SE, Schnabel CA, Sullivan PS, Zhang Y, Singh V, Carey B, Erlander M, Highsmith WE, Dry SM, Brachtel E.

Source

Laboratory Medicine and Pathology, Mayo Clinic.

Abstract

PURPOSE:

Accurate tumor classification is essential for cancer management as patient outcomes improve with use of site- and subtype-specific therapies. Current clinicopathological evaluation is varied in approach, yet standardized diagnoses are critical for determining therapy. While gene expression-based cancer classifiers may potentially meet this need, imperative to determining their application to patient care is validation in rigorously designed studies. Here, we examined the performance of a 92-gene molecular classifier in a large multi-institution cohort.

EXPERIMENTAL DESIGN:

Case selection incorporated specimens from over 50 subtypes, including a range of tumor grades, metastatic and primary tumors, and limited tissue samples. Formalin-fixed, paraffin-embedded tumors passed pathologist-adjudicated review between three institutions. Tumor classification using a 92-gene quantitative RT-PCR assay was performed on blinded tumor sections from 790 cases and compared with adjudicated diagnoses.

RESULTS:

The 92-gene assay demonstrated overall sensitivities of 87% for tumor type (95% CI, 84% to 89%) and 82% for subtype (95% CI, 79 to 85%). Analyses of metastatic tumors, high-grade tumors, or cases with limited tissue showed no decrease in comparative performance (P=0.16, 0.58, and 0.16). High specificity (96%-100%) was demonstrated for ruling in a primary tumor in organs commonly harboring metastases. The assay incorrectly excluded the adjudicated diagnosis in 5% of cases.

CONCLUSIONS:

The 92-gene assay demonstrated strong performance for accurate molecular classification of a diverse set of tumor histologies. Results support potential use of the assay as a standardized molecular adjunct to routine clinicopathological evaluation for tumor classification and primary site diagnosis.