Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups.

The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities i...

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Publicado en:Modern Pathology Vol. 30; no. 12; pp. 1748 - 1760
Autores principales: Parra-Herran, Carlos, Lerner-Ellis, Jordan, Xu, Bin, Khalouei, Sam, Bassiouny, Dina, Cesari, Matthew, Ismiil, Nadia, Nofech-Mozes, Sharon
Formato: Journal Article
Publicado: Elsevier B.V. Dec2017
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Dec2017
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      pub: Elsevier B.V.
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        10.1038/modpathol.2017.81
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        atl: Molecular-based classification algorithm for endometrial carcinoma categorizes ovarian endometrioid carcinoma into prognostically significant groups.
      aug:
        au:
          Parra-Herran, Carlos
          Lerner-Ellis, Jordan
          Xu, Bin
          Khalouei, Sam
          Bassiouny, Dina
          Cesari, Matthew
          Ismiil, Nadia
          Nofech-Mozes, Sharon
        affil: Department of Pathology and Laboratory Medicine, Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada
      sug:
        subj:
          Endometrial Neoplasms Classification
          Neoplasms, Glandular and Epithelial Classification
          Algorithms
          Ovarian Neoplasms Classification
          Endometrial Neoplasms Mortality
          Aged
          Endometrial Neoplasms
          Prognosis
          Middle Age
          Ovarian Neoplasms
          Neoplasms, Glandular and Epithelial Mortality
          Ovarian Neoplasms Mortality
          Aged, 80 and Over
          Adult
          Female
          Cox Proportional Hazards Model
          Neoplasms, Glandular and Epithelial
          Scales
          Aged: 65+ years
          Middle Aged: 45-64 years
          Aged, 80 & over
          Adult: 19-44 years
          Female
      ab: The Cancer Genome Atlas classification divides endometrial carcinoma in biologically distinct groups, and testing for p53, mismatch repair proteins (MMR), and polymerase ɛ (POLE) exonuclease domain mutations has been shown to predict the molecular subgroup and clinical outcome. While abnormalities in these markers have been described in ovarian endometrioid carcinoma, their role in predicting its molecular profile and prognosis is still not fully explored. Patients with ovarian endometrioid carcinomas treated surgically in a 14-year period were selected. Only tumors with confirmation of endometrioid histology and negative WT1 and Napsin-A were included. POLE mutational analysis and immunohistochemistry for p53, MLH1, MSH2, MSH6, and PMS2 was performed in formalin-fixed, paraffin-embedded tissue. Following the molecular classifier proposed for endometrial carcinoma (Br J Cancer2015;113:299-310), cases were classified as POLE mutated, MMR abnormal, p53 abnormal, and p53 wild type. Clinicopathologic information was recorded, including patient outcome. In all, 72 cases were included, distributed as follows: 7 (10%) POLE mutated; 6 (8%) MMR abnormal; 17 (24%) p53 abnormal; and 42 (58%) p53 wild type. The molecular classification correlated with disease-free survival in multivariate analysis (P=0.003), independently of tumor grade and stage. Correlation with overall survival approached statistical significance (P=0.051). POLE-mutated and MMR-abnormal tumors had excellent survival, whereas p53-abnormal tumors had significantly higher rates of recurrence and death. Ovarian endometroid carcinoma can be classified in clinically meaningful subgroups by testing for molecular surrogates, akin to endometrial cancer. MMR and POLE alterations seem to identify a subset of ovarian endometrioid carcinomas with excellent outcome; conversely, abnormal p53 carries a worse prognosis. In the era of personalized medicine, the use of these markers in the routine evaluation of ovarian endometrioid tumors should be considered.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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