TY - JOUR
T1 - Multisite validation study to determine performance characteristics of a 92-gene molecular cancer classifier
AU - Kerr, Sarah E.
AU - Schnabel, Catherine A.
AU - Sullivan, Peggy S.
AU - Zhang, Yi
AU - Singh, Veena
AU - Carey, Brittany
AU - Erlander, Mark G.
AU - Highsmith, W. Edward
AU - Dry, Sarah M.
AU - Brachtel, Elena F.
PY - 2012/7/15
Y1 - 2012/7/15
N2 - Purpose: Accurate tumor classification is essential for cancer management as patient outcomes improve with use of site- and subtype-specific therapies. Current clinicopathologic 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 more than 50 subtypes, including a range of tumor grades, metastatic and primary tumors, and limited tissue samples. Formalin-fixed, paraffinembedded tumors passed pathologist-adjudicated review between three institutions. Tumor classification using a 92-gene quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay was conducted on blinded tumor sections from 790 cases and compared with adjudicated diagnoses. Results: The 92-gene assay showed overall sensitivities of 87% for tumor type [95% confidence interval (CI), 84-89] and 82% for subtype (95% CI, 79-85). 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 showed 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 showed 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 clinicopathologic evaluation for tumor classification and primary site diagnosis.
AB - Purpose: Accurate tumor classification is essential for cancer management as patient outcomes improve with use of site- and subtype-specific therapies. Current clinicopathologic 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 more than 50 subtypes, including a range of tumor grades, metastatic and primary tumors, and limited tissue samples. Formalin-fixed, paraffinembedded tumors passed pathologist-adjudicated review between three institutions. Tumor classification using a 92-gene quantitative reverse transcriptase polymerase chain reaction (RT-PCR) assay was conducted on blinded tumor sections from 790 cases and compared with adjudicated diagnoses. Results: The 92-gene assay showed overall sensitivities of 87% for tumor type [95% confidence interval (CI), 84-89] and 82% for subtype (95% CI, 79-85). 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 showed 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 showed 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 clinicopathologic evaluation for tumor classification and primary site diagnosis.
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U2 - 10.1158/1078-0432.CCR-12-0920
DO - 10.1158/1078-0432.CCR-12-0920
M3 - Article
C2 - 22648269
AN - SCOPUS:84863911666
SN - 1078-0432
VL - 18
SP - 3952
EP - 3960
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 14
ER -