Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series

S. Kommoss, M. K. McConechy, F. Kommoss, S. Leung, A. Bunz, J. Magrill, H. Britton, F. Kommoss, F. Grevenkamp, Anthony Karnezis, W. Yang, A. Lum, B. Krämer, F. Taran, A. Staebler, S. Lax, S. Y. Brucker, D. G. Huntsman, C. B. Gilks, Jessica N. McAlpineA. Talhouk

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognosticmarker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, j 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

Original languageEnglish (US)
Pages (from-to)1180-1188
Number of pages9
JournalAnnals of Oncology
Volume29
Issue number5
DOIs
StatePublished - May 1 2018
Externally publishedYes

Fingerprint

Endometrial Neoplasms
National Academies of Science, Engineering, and Medicine (U.S.) Health and Medicine Division
Guidelines
Population
Neoplasms
Atlases
Disease-Free Survival
Disease Progression
Decision Making
Biomarkers
Clinical Trials
Genome
Biopsy
Survival
Therapeutics

Keywords

  • Biomarker
  • Endometrial cancer
  • Molecular classification
  • Prognosis

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Kommoss, S., McConechy, M. K., Kommoss, F., Leung, S., Bunz, A., Magrill, J., ... Talhouk, A. (2018). Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. Annals of Oncology, 29(5), 1180-1188. https://doi.org/10.1093/annonc/mdy058

Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. / Kommoss, S.; McConechy, M. K.; Kommoss, F.; Leung, S.; Bunz, A.; Magrill, J.; Britton, H.; Kommoss, F.; Grevenkamp, F.; Karnezis, Anthony; Yang, W.; Lum, A.; Krämer, B.; Taran, F.; Staebler, A.; Lax, S.; Brucker, S. Y.; Huntsman, D. G.; Gilks, C. B.; McAlpine, Jessica N.; Talhouk, A.

In: Annals of Oncology, Vol. 29, No. 5, 01.05.2018, p. 1180-1188.

Research output: Contribution to journalArticle

Kommoss, S, McConechy, MK, Kommoss, F, Leung, S, Bunz, A, Magrill, J, Britton, H, Kommoss, F, Grevenkamp, F, Karnezis, A, Yang, W, Lum, A, Krämer, B, Taran, F, Staebler, A, Lax, S, Brucker, SY, Huntsman, DG, Gilks, CB, McAlpine, JN & Talhouk, A 2018, 'Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series', Annals of Oncology, vol. 29, no. 5, pp. 1180-1188. https://doi.org/10.1093/annonc/mdy058
Kommoss, S. ; McConechy, M. K. ; Kommoss, F. ; Leung, S. ; Bunz, A. ; Magrill, J. ; Britton, H. ; Kommoss, F. ; Grevenkamp, F. ; Karnezis, Anthony ; Yang, W. ; Lum, A. ; Krämer, B. ; Taran, F. ; Staebler, A. ; Lax, S. ; Brucker, S. Y. ; Huntsman, D. G. ; Gilks, C. B. ; McAlpine, Jessica N. ; Talhouk, A. / Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series. In: Annals of Oncology. 2018 ; Vol. 29, No. 5. pp. 1180-1188.
@article{2afd472198534c0fa9160bbcc571c95d,
title = "Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series",
abstract = "Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the T{\"u}bingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8{\%} cases were endometrioid histotype. Grade distribution included 282 (62.4{\%}) G1, 75 (16.6{\%}) G2, and 95 (21.0{\%}) G3 tumors. 276 (61.1{\%}) patients had stage IA disease, with the remaining stage IB [89 (19.7{\%})], stage II [26 (5.8{\%})], and stage III/IV [61 (13.5{\%})]. ProMisE molecular classification yielded 127 (28.1{\%}) MMR-D, 42 (9.3{\%}) POLE, 55 (12.2{\%}) p53abn, and 228 (50.4{\%}) p53wt. ProMisE was a prognosticmarker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, j 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.",
keywords = "Biomarker, Endometrial cancer, Molecular classification, Prognosis",
author = "S. Kommoss and McConechy, {M. K.} and F. Kommoss and S. Leung and A. Bunz and J. Magrill and H. Britton and F. Kommoss and F. Grevenkamp and Anthony Karnezis and W. Yang and A. Lum and B. Kr{\"a}mer and F. Taran and A. Staebler and S. Lax and Brucker, {S. Y.} and Huntsman, {D. G.} and Gilks, {C. B.} and McAlpine, {Jessica N.} and A. Talhouk",
year = "2018",
month = "5",
day = "1",
doi = "10.1093/annonc/mdy058",
language = "English (US)",
volume = "29",
pages = "1180--1188",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Final validation of the ProMisE molecular classifier for endometrial carcinoma in a large population-based case series

AU - Kommoss, S.

AU - McConechy, M. K.

AU - Kommoss, F.

AU - Leung, S.

AU - Bunz, A.

AU - Magrill, J.

AU - Britton, H.

AU - Kommoss, F.

AU - Grevenkamp, F.

AU - Karnezis, Anthony

AU - Yang, W.

AU - Lum, A.

AU - Krämer, B.

AU - Taran, F.

AU - Staebler, A.

AU - Lax, S.

AU - Brucker, S. Y.

AU - Huntsman, D. G.

AU - Gilks, C. B.

AU - McAlpine, Jessica N.

AU - Talhouk, A.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognosticmarker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, j 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

AB - Background: We have previously developed and confirmed a pragmatic molecular classifier for endometrial cancers; ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer). Inspired by the Cancer Genome Atlas, ProMisE identifies four prognostically distinct molecular subtypes and can be applied to diagnostic specimens (biopsy/curettings) enabling earlier informed decision-making. We have strictly adhered to the Institute of Medicine (IOM) guidelines for the development of genomic biomarkers, and herein present the final validation step of a locked-down classifier before clinical application. Patients and methods: We assessed a retrospective cohort of women from the Tübingen University Women's Hospital treated for endometrial carcinoma between 2003 and 2013. Primary outcomes of overall, disease-specific, and progression-free survival were evaluated for clinical, pathological, and molecular features. Results: Complete clinical and molecular data were evaluable from 452 women. Patient age ranged from 29 to 93 (median 65) years, and 87.8% cases were endometrioid histotype. Grade distribution included 282 (62.4%) G1, 75 (16.6%) G2, and 95 (21.0%) G3 tumors. 276 (61.1%) patients had stage IA disease, with the remaining stage IB [89 (19.7%)], stage II [26 (5.8%)], and stage III/IV [61 (13.5%)]. ProMisE molecular classification yielded 127 (28.1%) MMR-D, 42 (9.3%) POLE, 55 (12.2%) p53abn, and 228 (50.4%) p53wt. ProMisE was a prognosticmarker for progression-free (P=0.001) and disease-specific (P=0.03) survival even after adjusting for known risk factors. Concordance between diagnostic and surgical specimens was highly favorable; accuracy 0.91, j 0.88. Discussion: We have developed, confirmed, and now validated a pragmatic molecular classification tool (ProMisE) that provides consistent categorization of tumors and identifies four distinct prognostic molecular subtypes. ProMisE can be applied to diagnostic samples and thus could be used to inform surgical procedure(s) and/or need for adjuvant therapy. Based on the IOM guidelines this classifier is now ready for clinical evaluation through prospective clinical trials.

KW - Biomarker

KW - Endometrial cancer

KW - Molecular classification

KW - Prognosis

UR - http://www.scopus.com/inward/record.url?scp=85047629147&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85047629147&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdy058

DO - 10.1093/annonc/mdy058

M3 - Article

C2 - 29432521

AN - SCOPUS:85047629147

VL - 29

SP - 1180

EP - 1188

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 5

ER -