A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors

Charles R. Handorf, Anand Kulkarni, James P. Grenert, Lawrence M. Weiss, William M. Rogers, Oliver S. Kim, Federico A. Monzon, Meredith Halks-Miller, Glenda G. Anderson, Michael G. Walker, Raji Pillai, W. David Henner

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-todiagnose tumors have never been directly compared with the diagnostic standard of care, immunochemistry (IHC). This prospectively conducted, blinded, multicenter study compares the diagnostic accuracy of GEP with IHC in identifying the primary site of 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known primaries, representing the 15 tissues on the GEP test panel. Four pathologists rendered diagnoses by selecting from 84 stains in 2 rounds. GEP was performed using the Pathwork Tissue of Origin Test. Overall, GEP accurately identified 89% of specimens, compared with 83% accuracy using IHC (P=0.013). In the subset of 33 poorly differentiated and undifferentiated carcinomas, GEP accuracy exceeded that of IHC (91% to 71%, P=0.023). In specimens for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90% accuracy. However, when the diagnosis required a second round, IHC significantly underperformed GEP (67% to 83%, P>0.001). GEP has been validated as accurate in diagnosing the primary site in metastatic tumors. The Pathwork Tissue of Origin Test used in this study was significantly more accurate than IHC when used to identify the primary site, with the most pronounced superiority observed in specimens that required a second round of stains and in poorly differentiated and undifferentiated metastatic carcinomas.

Original languageEnglish (US)
Pages (from-to)1067-1075
Number of pages9
JournalAmerican Journal of Surgical Pathology
Volume37
Issue number7
DOIs
StatePublished - Jul 1 2013

Fingerprint

Gene Expression Profiling
Multicenter Studies
Immunohistochemistry
Neoplasms
Coloring Agents
Standard of Care
Carcinoma
Immunochemistry
Paraffin
Formaldehyde

All Science Journal Classification (ASJC) codes

  • Anatomy
  • Surgery
  • Pathology and Forensic Medicine

Cite this

A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. / Handorf, Charles R.; Kulkarni, Anand; Grenert, James P.; Weiss, Lawrence M.; Rogers, William M.; Kim, Oliver S.; Monzon, Federico A.; Halks-Miller, Meredith; Anderson, Glenda G.; Walker, Michael G.; Pillai, Raji; Henner, W. David.

In: American Journal of Surgical Pathology, Vol. 37, No. 7, 01.07.2013, p. 1067-1075.

Research output: Contribution to journalArticle

Handorf, CR, Kulkarni, A, Grenert, JP, Weiss, LM, Rogers, WM, Kim, OS, Monzon, FA, Halks-Miller, M, Anderson, GG, Walker, MG, Pillai, R & Henner, WD 2013, 'A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors', American Journal of Surgical Pathology, vol. 37, no. 7, pp. 1067-1075. https://doi.org/10.1097/PAS.0b013e31828309c4
Handorf, Charles R. ; Kulkarni, Anand ; Grenert, James P. ; Weiss, Lawrence M. ; Rogers, William M. ; Kim, Oliver S. ; Monzon, Federico A. ; Halks-Miller, Meredith ; Anderson, Glenda G. ; Walker, Michael G. ; Pillai, Raji ; Henner, W. David. / A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors. In: American Journal of Surgical Pathology. 2013 ; Vol. 37, No. 7. pp. 1067-1075.
@article{e9b3fdcfaa864e3fb0e7c354a97d60a8,
title = "A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors",
abstract = "Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-todiagnose tumors have never been directly compared with the diagnostic standard of care, immunochemistry (IHC). This prospectively conducted, blinded, multicenter study compares the diagnostic accuracy of GEP with IHC in identifying the primary site of 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known primaries, representing the 15 tissues on the GEP test panel. Four pathologists rendered diagnoses by selecting from 84 stains in 2 rounds. GEP was performed using the Pathwork Tissue of Origin Test. Overall, GEP accurately identified 89{\%} of specimens, compared with 83{\%} accuracy using IHC (P=0.013). In the subset of 33 poorly differentiated and undifferentiated carcinomas, GEP accuracy exceeded that of IHC (91{\%} to 71{\%}, P=0.023). In specimens for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90{\%} accuracy. However, when the diagnosis required a second round, IHC significantly underperformed GEP (67{\%} to 83{\%}, P>0.001). GEP has been validated as accurate in diagnosing the primary site in metastatic tumors. The Pathwork Tissue of Origin Test used in this study was significantly more accurate than IHC when used to identify the primary site, with the most pronounced superiority observed in specimens that required a second round of stains and in poorly differentiated and undifferentiated metastatic carcinomas.",
author = "Handorf, {Charles R.} and Anand Kulkarni and Grenert, {James P.} and Weiss, {Lawrence M.} and Rogers, {William M.} and Kim, {Oliver S.} and Monzon, {Federico A.} and Meredith Halks-Miller and Anderson, {Glenda G.} and Walker, {Michael G.} and Raji Pillai and Henner, {W. David}",
year = "2013",
month = "7",
day = "1",
doi = "10.1097/PAS.0b013e31828309c4",
language = "English (US)",
volume = "37",
pages = "1067--1075",
journal = "American Journal of Surgical Pathology",
issn = "0147-5185",
publisher = "Lippincott Williams and Wilkins",
number = "7",

}

TY - JOUR

T1 - A multicenter study directly comparing the diagnostic accuracy of gene expression profiling and immunohistochemistry for primary site identification in metastatic tumors

AU - Handorf, Charles R.

AU - Kulkarni, Anand

AU - Grenert, James P.

AU - Weiss, Lawrence M.

AU - Rogers, William M.

AU - Kim, Oliver S.

AU - Monzon, Federico A.

AU - Halks-Miller, Meredith

AU - Anderson, Glenda G.

AU - Walker, Michael G.

AU - Pillai, Raji

AU - Henner, W. David

PY - 2013/7/1

Y1 - 2013/7/1

N2 - Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-todiagnose tumors have never been directly compared with the diagnostic standard of care, immunochemistry (IHC). This prospectively conducted, blinded, multicenter study compares the diagnostic accuracy of GEP with IHC in identifying the primary site of 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known primaries, representing the 15 tissues on the GEP test panel. Four pathologists rendered diagnoses by selecting from 84 stains in 2 rounds. GEP was performed using the Pathwork Tissue of Origin Test. Overall, GEP accurately identified 89% of specimens, compared with 83% accuracy using IHC (P=0.013). In the subset of 33 poorly differentiated and undifferentiated carcinomas, GEP accuracy exceeded that of IHC (91% to 71%, P=0.023). In specimens for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90% accuracy. However, when the diagnosis required a second round, IHC significantly underperformed GEP (67% to 83%, P>0.001). GEP has been validated as accurate in diagnosing the primary site in metastatic tumors. The Pathwork Tissue of Origin Test used in this study was significantly more accurate than IHC when used to identify the primary site, with the most pronounced superiority observed in specimens that required a second round of stains and in poorly differentiated and undifferentiated metastatic carcinomas.

AB - Metastatic tumors with an uncertain primary site can be a difficult clinical problem. In tens of thousands of patients every year, no confident diagnosis is ever issued, making standard-of-care treatment impossible. Gene expression profiling (GEP) tests currently available to analyze these difficult-todiagnose tumors have never been directly compared with the diagnostic standard of care, immunochemistry (IHC). This prospectively conducted, blinded, multicenter study compares the diagnostic accuracy of GEP with IHC in identifying the primary site of 157 formalin-fixed paraffin-embedded specimens from metastatic tumors with known primaries, representing the 15 tissues on the GEP test panel. Four pathologists rendered diagnoses by selecting from 84 stains in 2 rounds. GEP was performed using the Pathwork Tissue of Origin Test. Overall, GEP accurately identified 89% of specimens, compared with 83% accuracy using IHC (P=0.013). In the subset of 33 poorly differentiated and undifferentiated carcinomas, GEP accuracy exceeded that of IHC (91% to 71%, P=0.023). In specimens for which pathologists rendered their final diagnosis with a single round of stains, both IHC and GEP exceeded 90% accuracy. However, when the diagnosis required a second round, IHC significantly underperformed GEP (67% to 83%, P>0.001). GEP has been validated as accurate in diagnosing the primary site in metastatic tumors. The Pathwork Tissue of Origin Test used in this study was significantly more accurate than IHC when used to identify the primary site, with the most pronounced superiority observed in specimens that required a second round of stains and in poorly differentiated and undifferentiated metastatic carcinomas.

UR - http://www.scopus.com/inward/record.url?scp=84880314660&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84880314660&partnerID=8YFLogxK

U2 - 10.1097/PAS.0b013e31828309c4

DO - 10.1097/PAS.0b013e31828309c4

M3 - Article

VL - 37

SP - 1067

EP - 1075

JO - American Journal of Surgical Pathology

JF - American Journal of Surgical Pathology

SN - 0147-5185

IS - 7

ER -