Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

Kean Chang Phang, Ariz Akhter, Nur Maya Sabrina Tizen, Faridah Abd Rahman, Raja Zahratul Azma Raja Sabudin, Ghaleb Elyamany, Meer Taher Shabani-Rad, Noraidah Masir, Adnan Mansoor

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.

METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).

RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).

CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

Original languageEnglish
Pages (from-to)215-220
Number of pages6
JournalJournal of Clinical Pathology
Volume71
Issue number3
DOIs
Publication statusPublished - 1 Mar 2018
Externally publishedYes

Fingerprint

Lymphoma, Large B-Cell, Diffuse
Malaysia
B-Lymphocytes
RNA
Germinal Center
Proteins
Pathology
Technology
Biopsy

Keywords

  • Cell of origin
  • Diffuse large B-cell lymphoma
  • DLBCL -ACB subtype
  • DLBCL -GCB subtype
  • Hans algorithm.
  • Lymph2Cx

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia. / Phang, Kean Chang; Akhter, Ariz; Tizen, Nur Maya Sabrina; Rahman, Faridah Abd; Raja Sabudin, Raja Zahratul Azma; Elyamany, Ghaleb; Shabani-Rad, Meer Taher; Masir, Noraidah; Mansoor, Adnan.

In: Journal of Clinical Pathology, Vol. 71, No. 3, 01.03.2018, p. 215-220.

Research output: Contribution to journalArticle

Phang, Kean Chang ; Akhter, Ariz ; Tizen, Nur Maya Sabrina ; Rahman, Faridah Abd ; Raja Sabudin, Raja Zahratul Azma ; Elyamany, Ghaleb ; Shabani-Rad, Meer Taher ; Masir, Noraidah ; Mansoor, Adnan. / Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia. In: Journal of Clinical Pathology. 2018 ; Vol. 71, No. 3. pp. 215-220.
@article{e46a35814a4b4f94942cfcd7fdba0659,
title = "Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia",
abstract = "AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).RESULTS: 96 (92{\%}) informative samples were labelled as GCB (38/96; 40{\%}) and non-GCB (58/96; 60{\%}) by IHC evaluation. Lymph2Cx catalogued 36/96 (37{\%}) samples as GCB, 45/96 (47{\%}) as ABC and 15/96 (16{\%}) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81{\%} for ABC and 75{\%} for GCB categorisation and positive predictive value of 81{\%} versus 82{\%}, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.",
keywords = "Cell of origin, Diffuse large B-cell lymphoma, DLBCL -ACB subtype, DLBCL -GCB subtype, Hans algorithm., Lymph2Cx",
author = "Phang, {Kean Chang} and Ariz Akhter and Tizen, {Nur Maya Sabrina} and Rahman, {Faridah Abd} and {Raja Sabudin}, {Raja Zahratul Azma} and Ghaleb Elyamany and Shabani-Rad, {Meer Taher} and Noraidah Masir and Adnan Mansoor",
year = "2018",
month = "3",
day = "1",
doi = "10.1136/jclinpath-2017-204548",
language = "English",
volume = "71",
pages = "215--220",
journal = "Journal of Clinical Pathology - Clinical Molecular Pathology",
issn = "0021-9746",
publisher = "BMJ Publishing Group",
number = "3",

}

TY - JOUR

T1 - Comparison of protein-based cell-of-origin classification to the Lymph2Cx RNA assay in a cohort of diffuse large B-cell lymphomas in Malaysia

AU - Phang, Kean Chang

AU - Akhter, Ariz

AU - Tizen, Nur Maya Sabrina

AU - Rahman, Faridah Abd

AU - Raja Sabudin, Raja Zahratul Azma

AU - Elyamany, Ghaleb

AU - Shabani-Rad, Meer Taher

AU - Masir, Noraidah

AU - Mansoor, Adnan

PY - 2018/3/1

Y1 - 2018/3/1

N2 - AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

AB - AIMS: The cell of origin (COO) based molecular characterisation into germinal centre B-cell-like (GCB) and activated B-cell-like (ABC) subtypes are central to the pathogenesis and clinical course in diffuse large B-cell lymphoma (DLBCL). Globally, clinical laboratories employ pragmatic but less than ideal immunohistochemical (IHC) assay for COO classification. Novel RNA-based platforms using routine pathology samples are emerging as new gold standard and offer unique opportunities for assay standardisation for laboratories across the world. We evaluated our IHC protocols against RNA-based technologies to determine concordance; additionally, we gauged the impact of preanalytical variation on the performance of Lymph2Cx assay.METHODS: Diagnostic biopsies (n=104) were examined for COO classification, employing automated RNA digital quantification assay (Lymph2Cx). Results were equated against IHC-based COO categorisation. Assay performance was assessed through its impact on overall survival (OS).RESULTS: 96 (92%) informative samples were labelled as GCB (38/96; 40%) and non-GCB (58/96; 60%) by IHC evaluation. Lymph2Cx catalogued 36/96 (37%) samples as GCB, 45/96 (47%) as ABC and 15/96 (16%) as unclassified. Lymph2Cx being reference, IHC protocol revealed sensitivity of 81% for ABC and 75% for GCB categorisation and positive predictive value of 81% versus 82%, respectively. Lymph2Cx-based COO classification performed superior to Hans algorithm in predicting OS (log rank test, p=0.017 vs p=0.212).CONCLUSIONS: Our report show that current IHC-based protocols for COO classification of DLBCL at UKM Malaysia are in line with previously reported results and marked variation in preanalytical factors do not critically impact Lymph2Cx assay quality.

KW - Cell of origin

KW - Diffuse large B-cell lymphoma

KW - DLBCL -ACB subtype

KW - DLBCL -GCB subtype

KW - Hans algorithm.

KW - Lymph2Cx

UR - http://www.scopus.com/inward/record.url?scp=85030839834&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85030839834&partnerID=8YFLogxK

U2 - 10.1136/jclinpath-2017-204548

DO - 10.1136/jclinpath-2017-204548

M3 - Article

C2 - 28775174

AN - SCOPUS:85030839834

VL - 71

SP - 215

EP - 220

JO - Journal of Clinical Pathology - Clinical Molecular Pathology

JF - Journal of Clinical Pathology - Clinical Molecular Pathology

SN - 0021-9746

IS - 3

ER -