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      Correlation of World Health Organization 2010 Classification for Gastroenteropancreatic Neuroendocrine Neoplasms with the Prognosis of Ovarian Neuroendocrine Neoplasms: Kansai Clinical Oncology Group-Protocol Review Committee/Intergroup Study

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          Abstract

          Background: In 2014, the World Health Organization (WHO) released a classification system introducing neuroendocrine neoplasms (NENs) of the female reproductive tract, excluding the ovaries. This study aimed to evaluate whether retrospective adaption of the gastroenteropancreatic (GEP)-NEN classification is feasible for ovarian NENs (O-NENs) and correlates with prognosis. Methods: Sixty-eight patients diagnosed with carcinoid, small cell carcinoma (pulmonary type), paraganglioma, non-small/large cell neuroendocrine carcinoma (NEC), mixed NEC, or undifferentiated carcinomas at 20 institutions in Japan were included in this retrospective cross-sectional study. We identified O-NENs through central pathological review using a common slide set, followed by reclassification according to WHO 2010 guidelines for GEP-NENs. A proportional hazards model was used to assess the association of prognostic factors (age, stage, performance status, histology, and residual disease) with overall survival (OS) and progression-free survival (PFS). Results: Of the 68 enrolled patients, 48 were eligible for analysis. All carcinoids ( n = 32) were reclassified as NET G1/G2, whereas 14 of 16 carcinomas were reclassified as NEC/mixed adeno-NEC (MANEC) (Fisher’s exact test; p < 0.01). The OS/PFS was 49.0/42.5 months and 6.5/3.9 months for NET G1/G2 and NEC/MANEC, respectively. Histology revealed that NEC/MANEC was associated with increased risk of death (HR = 48.0; 95% CI, 3.93–586; p < 0.01) and disease progression (HR = 51.6; 95% CI, 5.54–480; p < 0.01). Conclusion: Retrospective adaption of GEP-NEN classification to O-NENs is feasible and correlates well with the prognosis of O-NENs. This classification could be introduced for ovarian tumors.

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          Most cited references 23

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          Toxicity and response criteria of the Eastern Cooperative Oncology Group.

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              Is Open Access

              A common classification framework for neuroendocrine neoplasms: an International Agency for Research on Cancer (IARC) and World Health Organization (WHO) expert consensus proposal

              The classification of neuroendocrine neoplasms (NENs) differs between organ systems and currently causes considerable confusion. A uniform classification framework for NENs at any anatomical location may reduce inconsistencies and contradictions among the various systems currently in use. The classification suggested here is intended to allow pathologists and clinicians to manage their patients with NENs consistently, while acknowledging organ-specific differences in classification criteria, tumor biology, and prognostic factors. The classification suggested is based on a consensus conference held at the International Agency for Research on Cancer (IARC) in November 2017 and subsequent discussion with additional experts. The key feature of the new classification is a distinction between differentiated neuroendocrine tumors (NETs), also designated carcinoid tumors in some systems, and poorly differentiated NECs, as they both share common expression of neuroendocrine markers. This dichotomous morphological subdivision into NETs and NECs is supported by genetic evidence at specific anatomic sites as well as clinical, epidemiologic, histologic, and prognostic differences. In many organ systems, NETs are graded as G1, G2, or G3 based on mitotic count and/or Ki-67 labeling index, and/or the presence of necrosis; NECs are considered high grade by definition. We believe this conceptual approach can form the basis for the next generation of NEN classifications and will allow more consistent taxonomy to understand how neoplasms from different organ systems inter-relate clinically and genetically.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2021
                March 2021
                25 February 2020
                : 111
                : 4
                : 320-329
                Affiliations
                aDepartment of Obstetrics and Gynecology, Faculty of Medicine, Oita University, Yufu, Japan
                bDivision of Obstetrics and Gynecology, Support System for Community Medicine, Faculty of Medicine, Oita University, Yufu, Japan
                cDepartment of Diagnostic Pathology, Faculty of Medicine, Oita University, Yufu, Japan
                dDepartment of Obstetrics and Gynecology, University of Tsukuba, Tsukuba, Japan
                eDivision of Gynecology, Hyogo Cancer Center, Akashi, Japan
                fDepartment of Obstetrics and Gynecology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan
                gDepartment of Pathology, Saitama Medical University International Medical Center, Hidaka, Japan
                hDepartment of Obstetrics and Gynecology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
                iDepartment of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, Sendai, Japan
                jDepartment of Obstetrics and Gynecology, Kurume University School of Medicine, Kurume, Japan
                kDepartment of Obstetrics and Gynecology, The Jikei University School of Medicine, Minato, Japan
                lDepartment of Obstetrics and Gynecology, Nara Medical University, Kashihara, Japan
                mDepartment of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Japan
                nDepartment of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Japan
                oDepartment of Gynecologic oncology, National Hospital Organization Shikoku Cancer Center, Matsuyama, Japan
                pDepartment of Obstetrics and Gynecology, Kansai Rosai Hospital, Amagasaki, Japan
                qDepartment of Obstetrics and Gynecology, Nagoya City University Graduate School of Medicine, Nagoya, Japan
                rDepartment of Obstetrics and Gynecology, Faculty of MedicineTottori University, Yonago, Japan
                sDepartment of Obstetrics and Gynecology, Kochi University Kochi Medical School, Nankoku, Japan
                tDepartment of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Kyoto, Japan
                uChairperson, Kansai Clinical Oncology Group (KCOG), Osaka, Japan
                vDivision Director of Gynecology, Kansai Clinical Oncology Group (KCOG), Osaka, Japan
                wDivision head of Cancer Prevention and Epidemiology, Center for Clinical Research, Shikoku Cancer Center, Matsuyama, Japan
                xDepartment of Pathology, Osaka Medical College, Takatsuki, Japan
                Author notes
                *Dr. Kentaro Kai, Department of Obstetrics and Gynecology, Faculty of Medicine, Oita University, 1-1 Idaigaoka, Hasama-machi, Yufu City, Oita 879-5593 (Japan), kenta9sp@oita-u.ac.jp
                Article
                506743 Neuroendocrinology 2021;111:320–329
                10.1159/000506743
                32097950
                © 2020 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 3, Tables: 7, Pages: 10
                Categories
                Research Article

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