Cargando…
Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study
Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aim...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519469/ https://www.ncbi.nlm.nih.gov/pubmed/37746995 http://dx.doi.org/10.1097/MD.0000000000035022 |
_version_ | 1785109704827994112 |
---|---|
author | Kaneko, Masanao Nakashima, Mitsuko Sugiura, Kiichi Ishida, Natsuki Tamura, Satoshi Tani, Shinya Yamade, Mihoko Hamaya, Yasushi Osawa, Satoshi Tatsuta, Kyota Kurachi, Kiyotaka Baba, Satoshi Iwashita, Yuji Arai, Tomio Sugimura, Haruhiko Maekawa, Masato Sugimoto, Ken Iwaizumi, Moriya |
author_facet | Kaneko, Masanao Nakashima, Mitsuko Sugiura, Kiichi Ishida, Natsuki Tamura, Satoshi Tani, Shinya Yamade, Mihoko Hamaya, Yasushi Osawa, Satoshi Tatsuta, Kyota Kurachi, Kiyotaka Baba, Satoshi Iwashita, Yuji Arai, Tomio Sugimura, Haruhiko Maekawa, Masato Sugimoto, Ken Iwaizumi, Moriya |
author_sort | Kaneko, Masanao |
collection | PubMed |
description | Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression. |
format | Online Article Text |
id | pubmed-10519469 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-105194692023-09-26 Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study Kaneko, Masanao Nakashima, Mitsuko Sugiura, Kiichi Ishida, Natsuki Tamura, Satoshi Tani, Shinya Yamade, Mihoko Hamaya, Yasushi Osawa, Satoshi Tatsuta, Kyota Kurachi, Kiyotaka Baba, Satoshi Iwashita, Yuji Arai, Tomio Sugimura, Haruhiko Maekawa, Masato Sugimoto, Ken Iwaizumi, Moriya Medicine (Baltimore) 4500 Although immunohistochemistry (IHC) for mismatch repair (MMR) proteins (MMR IHC) is used to identify DNA MMR status, universal screening of all patients with colorectal cancer (CRC) using a combination of both MMR IHC and genetic testing for the BRAFV600E mutation is limited in Japan. This study aimed to better understand the histopathological characteristics of CRCs, which exhibit both deficient mismatch repair (dMMR) and BRAFV600E mutation. MMR IHC of formalin-fixed paraffin-embedded tissues from tumor areas obtained from 651 patients with CRC who underwent surgical resection at Hamamatsu University Hospital (Hamamatsu, Japan) between August 2016 and March 2022 were used to evaluate MMR status, which was determined by staining for the expression of 4 MMR proteins (MLH1, MSH2, PMS2, and MSH6). All dMMR tumors were additionally evaluated for BRAFV600 mutation status via Sanger sequencing. Patient clinical characteristics (age, sex, tumor location, size, and tumor pathology) were then classified using their dMMR and BRAFV600 mutation statuses. Among the 651 patients with CRC, 58 carried tumors with dMMR, of which 52 were deficiency in MLH1 (dMLH1). Interestingly, all 16 medullary carcinomas that were analyzed showed characteristics corresponding to the presence of both dMLH1 and BRAFV600E mutation (P = .01). These results suggest that colorectal medullary carcinomas can be diagnosed based on their unique characteristics of harboring the BRAFV600E mutation and exhibiting dMLH1 expression. Lippincott Williams & Wilkins 2023-09-22 /pmc/articles/PMC10519469/ /pubmed/37746995 http://dx.doi.org/10.1097/MD.0000000000035022 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. |
spellingShingle | 4500 Kaneko, Masanao Nakashima, Mitsuko Sugiura, Kiichi Ishida, Natsuki Tamura, Satoshi Tani, Shinya Yamade, Mihoko Hamaya, Yasushi Osawa, Satoshi Tatsuta, Kyota Kurachi, Kiyotaka Baba, Satoshi Iwashita, Yuji Arai, Tomio Sugimura, Haruhiko Maekawa, Masato Sugimoto, Ken Iwaizumi, Moriya Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title | Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title_full | Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title_fullStr | Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title_full_unstemmed | Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title_short | Both MLH1 deficiency and BRAFV600E mutation are a unique characteristic of colorectal medullary carcinoma: An observational study |
title_sort | both mlh1 deficiency and brafv600e mutation are a unique characteristic of colorectal medullary carcinoma: an observational study |
topic | 4500 |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10519469/ https://www.ncbi.nlm.nih.gov/pubmed/37746995 http://dx.doi.org/10.1097/MD.0000000000035022 |
work_keys_str_mv | AT kanekomasanao bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT nakashimamitsuko bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT sugiurakiichi bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT ishidanatsuki bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT tamurasatoshi bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT tanishinya bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT yamademihoko bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT hamayayasushi bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT osawasatoshi bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT tatsutakyota bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT kurachikiyotaka bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT babasatoshi bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT iwashitayuji bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT araitomio bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT sugimuraharuhiko bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT maekawamasato bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT sugimotoken bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy AT iwaizumimoriya bothmlh1deficiencyandbrafv600emutationareauniquecharacteristicofcolorectalmedullarycarcinomaanobservationalstudy |