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Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix

BACKGROUND: Primary grade 2 neuroendocrine tumors of the cervix in female patients are rare and have a highly aggressive clinical course. This study is aimed to analyse the diagnosis, genetic changes, management and prognosis of these tumors and investigate whether the genetic alterations could prov...

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Autores principales: Zhu, Ran, Wu, Huanwen, Chen, Bo, Pang, Junyi, Huo, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589179/
https://www.ncbi.nlm.nih.gov/pubmed/31228945
http://dx.doi.org/10.1186/s13000-019-0837-x
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author Zhu, Ran
Wu, Huanwen
Chen, Bo
Pang, Junyi
Huo, Zhen
author_facet Zhu, Ran
Wu, Huanwen
Chen, Bo
Pang, Junyi
Huo, Zhen
author_sort Zhu, Ran
collection PubMed
description BACKGROUND: Primary grade 2 neuroendocrine tumors of the cervix in female patients are rare and have a highly aggressive clinical course. This study is aimed to analyse the diagnosis, genetic changes, management and prognosis of these tumors and investigate whether the genetic alterations could provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors. METHODS: The clinical records of all three patients diagnosed as primary grade 2 neuroendocrine tumors of the cervix in Peking Union Medical College Hospital (PUMCH) from 2011 to 2018 were reviewed retrospectively. We investigated the morphology, immunophenotype and molecular abnormalities of all the cases. The follow-up data were also collected. RESULTS: The age of the patients ranged from 46 to 69 years. All cases were in stage II and treated with surgery. The microscopic examination showed that the tumors took the form of nest-like, trabecular, sheet-like, “single file” strands or rosette-like structures. The mitotic figures ranged from 2 to 5 in every 10 high-power fields, and necrotic foci were observed in one case. Immunohistochemically, the tumor cells were positive for AE1/AE3, Cg A, Syn, CD56, P16, CAM5.2, and PGP9.5 and negative for ER, PR, P63, P40, CK7, and CK20. The expression of P53 showed as normal/wild-type pattern, and the proliferation index of Ki-67 ranged from 2 to 7%. A total of 560 genes were sequenced by next-generation sequencing for each patient, and nonsynonymous somatic mutations were identified in the three cases. Non-frameshift insertions of the MAGI1 and SLC45A were both observed in case 1, while we only observed the non-frameshift insertion of the MAGI1 in case 2 and the non-frameshift insertion of the SLC45A in case 3. Case 1 was treated with chemoradiotherapy before and after surgery. Cases 2 and 3 were treated with chemotherapy before and after surgery. The follow-up time ranged from 27 to 74 months. Cases 2 and 3 survived, while case 1 died. CONCLUSION: Cervical grade 2 neuroendocrine tumors are extremely rare. We presented the first mutation profile revealed by whole exome sequencing in a series of grade 2 cervical NETs along with their clinicopathological characteristics. Their genetic changes are different from those that take place in the gastrointestinal tract, pancreas and lung, which have gene changes in VEGF, RTKs or the mTOR signalling pathway. While changes in MAGI1 and SLC45L3 were observed in two of our cases and the case who had the gene changes of both MAGI1 and SLC45L3 died because of metastases to the liver and bone. The genetic alterations may provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors.
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spelling pubmed-65891792019-06-24 Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix Zhu, Ran Wu, Huanwen Chen, Bo Pang, Junyi Huo, Zhen Diagn Pathol Research BACKGROUND: Primary grade 2 neuroendocrine tumors of the cervix in female patients are rare and have a highly aggressive clinical course. This study is aimed to analyse the diagnosis, genetic changes, management and prognosis of these tumors and investigate whether the genetic alterations could provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors. METHODS: The clinical records of all three patients diagnosed as primary grade 2 neuroendocrine tumors of the cervix in Peking Union Medical College Hospital (PUMCH) from 2011 to 2018 were reviewed retrospectively. We investigated the morphology, immunophenotype and molecular abnormalities of all the cases. The follow-up data were also collected. RESULTS: The age of the patients ranged from 46 to 69 years. All cases were in stage II and treated with surgery. The microscopic examination showed that the tumors took the form of nest-like, trabecular, sheet-like, “single file” strands or rosette-like structures. The mitotic figures ranged from 2 to 5 in every 10 high-power fields, and necrotic foci were observed in one case. Immunohistochemically, the tumor cells were positive for AE1/AE3, Cg A, Syn, CD56, P16, CAM5.2, and PGP9.5 and negative for ER, PR, P63, P40, CK7, and CK20. The expression of P53 showed as normal/wild-type pattern, and the proliferation index of Ki-67 ranged from 2 to 7%. A total of 560 genes were sequenced by next-generation sequencing for each patient, and nonsynonymous somatic mutations were identified in the three cases. Non-frameshift insertions of the MAGI1 and SLC45A were both observed in case 1, while we only observed the non-frameshift insertion of the MAGI1 in case 2 and the non-frameshift insertion of the SLC45A in case 3. Case 1 was treated with chemoradiotherapy before and after surgery. Cases 2 and 3 were treated with chemotherapy before and after surgery. The follow-up time ranged from 27 to 74 months. Cases 2 and 3 survived, while case 1 died. CONCLUSION: Cervical grade 2 neuroendocrine tumors are extremely rare. We presented the first mutation profile revealed by whole exome sequencing in a series of grade 2 cervical NETs along with their clinicopathological characteristics. Their genetic changes are different from those that take place in the gastrointestinal tract, pancreas and lung, which have gene changes in VEGF, RTKs or the mTOR signalling pathway. While changes in MAGI1 and SLC45L3 were observed in two of our cases and the case who had the gene changes of both MAGI1 and SLC45L3 died because of metastases to the liver and bone. The genetic alterations may provide more useful information to guide the molecular characterization and potential individualized treatment of grade 2 cervical neuroendocrine tumors. BioMed Central 2019-06-22 /pmc/articles/PMC6589179/ /pubmed/31228945 http://dx.doi.org/10.1186/s13000-019-0837-x Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhu, Ran
Wu, Huanwen
Chen, Bo
Pang, Junyi
Huo, Zhen
Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title_full Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title_fullStr Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title_full_unstemmed Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title_short Clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
title_sort clinicopathological characteristics and molecular abnormalities of primary grade 2 neuroendocrine tumors of the cervix
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6589179/
https://www.ncbi.nlm.nih.gov/pubmed/31228945
http://dx.doi.org/10.1186/s13000-019-0837-x
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