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Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer.
Cancer. 2017 03 01; 123(5):802-813.C

Abstract

BACKGROUND

Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs.

METHODS

Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples. Subgroups were characterized and assessed relative to outcomes. The prognostic ability of ProMisE was compared with that of current risk-stratification systems (European Society of Medical Oncology [ESMO]).

RESULTS

ProMisE decision-tree classification achieved categorization of all cases and identified 4 prognostic subgroups with distinct overall, disease-specific, and progression-free survival (P < .001). Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR-D) was observed. There were no significant differences in survival between the ESMO low-risk and intermediate-risk groups. ProMisE improved the ability to discriminate outcomes compared with ESMO risk stratification. There was substantial overlap (89%) between the p53 abn and high-risk ESMO subgroups; but, otherwise, there were no predictable associations between molecular and ESMO risk groups.

CONCLUSIONS

Molecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established clinicopathologic risk factors available at diagnosis. Consistent, biologically relevant categorization enables stratification for clinical trials and/or targeted therapy, identification of women who are at increased risk of having Lynch syndrome, and may guide clinical management. Cancer 2017;123:802-13. © 2016 American Cancer Society.

Authors+Show Affiliations

Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Human Genetics, McGill University, Research Institute of the McGill University Health Network, Montreal, Quebec, Canada.Genetic Pathology Evaluation Center, Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and British Columbia Cancer Agency, Vancouver, British Columbia, Canada.Department of Pathology and Laboratory Medicine, University of British Columbia and Vancouver General Hospital, Vancouver, British Columbia, Canada.Department of Gynecology and Obstetrics, Division of Gynecologic Oncology, University of British Columbia, Vancouver, British Columbia, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28061006

Citation

Talhouk, Aline, et al. "Confirmation of ProMisE: a Simple, Genomics-based Clinical Classifier for Endometrial Cancer." Cancer, vol. 123, no. 5, 2017, pp. 802-813.
Talhouk A, McConechy MK, Leung S, et al. Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer. 2017;123(5):802-813.
Talhouk, A., McConechy, M. K., Leung, S., Yang, W., Lum, A., Senz, J., Boyd, N., Pike, J., Anglesio, M., Kwon, J. S., Karnezis, A. N., Huntsman, D. G., Gilks, C. B., & McAlpine, J. N. (2017). Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. Cancer, 123(5), 802-813. https://doi.org/10.1002/cncr.30496
Talhouk A, et al. Confirmation of ProMisE: a Simple, Genomics-based Clinical Classifier for Endometrial Cancer. Cancer. 2017 03 1;123(5):802-813. PubMed PMID: 28061006.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Confirmation of ProMisE: A simple, genomics-based clinical classifier for endometrial cancer. AU - Talhouk,Aline, AU - McConechy,Melissa K, AU - Leung,Samuel, AU - Yang,Winnie, AU - Lum,Amy, AU - Senz,Janine, AU - Boyd,Niki, AU - Pike,Judith, AU - Anglesio,Michael, AU - Kwon,Janice S, AU - Karnezis,Anthony N, AU - Huntsman,David G, AU - Gilks,C Blake, AU - McAlpine,Jessica N, Y1 - 2017/01/06/ PY - 2016/08/05/received PY - 2016/10/04/revised PY - 2016/10/05/accepted PY - 2017/1/7/pubmed PY - 2017/5/30/medline PY - 2017/1/7/entrez KW - The Cancer Genome Atlas (TCGA) KW - endometrial carcinoma KW - histotype KW - mismatch repair KW - p53 KW - polymerase-ɛ (POLE) KW - prognostic KW - risk-stratification system SP - 802 EP - 813 JF - Cancer JO - Cancer VL - 123 IS - 5 N2 - BACKGROUND: Classification of endometrial carcinomas (ECs) by morphologic features is irreproducible and imperfectly reflects tumor biology. The authors developed the Proactive Molecular Risk Classifier for Endometrial Cancer (ProMisE), a molecular classification system based on The Cancer Genome Atlas genomic subgroups, and sought to confirm both feasibility and prognostic ability in a new, large cohort of ECs. METHODS: Immunohistochemistry (IHC) for the presence or absence of mismatch repair (MMR) proteins (to identify MMR deficiency [MMR-D]), sequencing for polymerase-ɛ (POLE) exonuclease domain mutations (POLE EDMs), and IHC for tumor protein 53 (p53) (wild type vs null/missense mutations; p53 wt and p53 abn, respectively) were performed on 319 new EC samples. Subgroups were characterized and assessed relative to outcomes. The prognostic ability of ProMisE was compared with that of current risk-stratification systems (European Society of Medical Oncology [ESMO]). RESULTS: ProMisE decision-tree classification achieved categorization of all cases and identified 4 prognostic subgroups with distinct overall, disease-specific, and progression-free survival (P < .001). Tumors with POLE EDMs had the most favorable prognosis, and those with p53 abn the worst prognosis, and separation of the 2 middle survival curves (p53 wt and MMR-D) was observed. There were no significant differences in survival between the ESMO low-risk and intermediate-risk groups. ProMisE improved the ability to discriminate outcomes compared with ESMO risk stratification. There was substantial overlap (89%) between the p53 abn and high-risk ESMO subgroups; but, otherwise, there were no predictable associations between molecular and ESMO risk groups. CONCLUSIONS: Molecular classification of ECs can be achieved using clinically applicable methods and provides independent prognostic information beyond established clinicopathologic risk factors available at diagnosis. Consistent, biologically relevant categorization enables stratification for clinical trials and/or targeted therapy, identification of women who are at increased risk of having Lynch syndrome, and may guide clinical management. Cancer 2017;123:802-13. © 2016 American Cancer Society. SN - 1097-0142 UR - https://www.unboundmedicine.com/medline/citation/28061006/Confirmation_of_ProMisE:_A_simple_genomics_based_clinical_classifier_for_endometrial_cancer_ L2 - https://doi.org/10.1002/cncr.30496 DB - PRIME DP - Unbound Medicine ER -