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High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients

The frequency of KRAS/BRAF mutations associated with low-grade serous ovarian carcinoma (LGSC)/serous borderline tumors (SBTs) in Japan is unknown. We aimed to identify genetic variations in KRAS, BRAF, PIK3CA, and ERBB2 in LGSC/SBT/serous cystadenomas (SCAs) in a Japanese population. We performed a...

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Autores principales: Ishibashi, Tomoka, Nakayama, Kentaro, Razia, Sultana, Ishikawa, Masako, Nakamura, Kohei, Yamashita, Hitomi, Dey, Puja, Iida, Koji, Kurioka, Hiroko, Nakayama, Satoru, Otsuki, Yoshiro, Ishikawa, Noriyoshi, Kyo, Satoru
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168240/
https://www.ncbi.nlm.nih.gov/pubmed/31892193
http://dx.doi.org/10.3390/diagnostics10010013
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author Ishibashi, Tomoka
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Nakamura, Kohei
Yamashita, Hitomi
Dey, Puja
Iida, Koji
Kurioka, Hiroko
Nakayama, Satoru
Otsuki, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
author_facet Ishibashi, Tomoka
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Nakamura, Kohei
Yamashita, Hitomi
Dey, Puja
Iida, Koji
Kurioka, Hiroko
Nakayama, Satoru
Otsuki, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
author_sort Ishibashi, Tomoka
collection PubMed
description The frequency of KRAS/BRAF mutations associated with low-grade serous ovarian carcinoma (LGSC)/serous borderline tumors (SBTs) in Japan is unknown. We aimed to identify genetic variations in KRAS, BRAF, PIK3CA, and ERBB2 in LGSC/SBT/serous cystadenomas (SCAs) in a Japanese population. We performed a mutation analysis (by Sanger sequencing) of 33 cases of LGSC/SBT/SCA and 4 cases of LGSC with synchronous SBTs using microdissected paraffin-embedded sections. Immunohistochemistry of p53 and ARID1A was also performed. The frequency of oncogenic mutations in PIK3CA was 60.0% (6/10) in LGSCs, 63.6% (7/11) in SBTs, and 8.3% (1/12) in SCAs. All cases harbored wild-type KRAS. The frequency of BRAF mutations was 20.0% (2/10) in LGSCs, whereas all SBTs and SCAs harbored the wild-type allele. The frequency of ERBB2 mutations was 30.0% (3/10) in LGSCs, 0.0% (0/11) in SBTs, and 16.7% (2/12) in SCAs. ARID1A staining was positive in all cases. p53 staining was positive in 0% (0/10) LGSCs, 9.1% (1/11) SBTs, and 0.0% (0/12) SCAs. One LGSC case had two PIK3CA mutations (G1633A and G3149A) in both LGSC and SBT lesions, but a BRAF mutation was detected only in an LGSC lesion. These results suggest that, compared with the values in Western populations (16–54%), the KRAS mutation frequency in LGSCs/SBTs is lower and that of PIK3CA mutations in LGSCs/SBTs is much higher in Japanese populations. Therefore, the main carcinogenesis signaling pathways may be different between Japanese and Western LGSCs. Molecular therapies targeting the PIK3CA/AKT pathway may be effective in LGSCs in Japan.
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spelling pubmed-71682402020-04-22 High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients Ishibashi, Tomoka Nakayama, Kentaro Razia, Sultana Ishikawa, Masako Nakamura, Kohei Yamashita, Hitomi Dey, Puja Iida, Koji Kurioka, Hiroko Nakayama, Satoru Otsuki, Yoshiro Ishikawa, Noriyoshi Kyo, Satoru Diagnostics (Basel) Article The frequency of KRAS/BRAF mutations associated with low-grade serous ovarian carcinoma (LGSC)/serous borderline tumors (SBTs) in Japan is unknown. We aimed to identify genetic variations in KRAS, BRAF, PIK3CA, and ERBB2 in LGSC/SBT/serous cystadenomas (SCAs) in a Japanese population. We performed a mutation analysis (by Sanger sequencing) of 33 cases of LGSC/SBT/SCA and 4 cases of LGSC with synchronous SBTs using microdissected paraffin-embedded sections. Immunohistochemistry of p53 and ARID1A was also performed. The frequency of oncogenic mutations in PIK3CA was 60.0% (6/10) in LGSCs, 63.6% (7/11) in SBTs, and 8.3% (1/12) in SCAs. All cases harbored wild-type KRAS. The frequency of BRAF mutations was 20.0% (2/10) in LGSCs, whereas all SBTs and SCAs harbored the wild-type allele. The frequency of ERBB2 mutations was 30.0% (3/10) in LGSCs, 0.0% (0/11) in SBTs, and 16.7% (2/12) in SCAs. ARID1A staining was positive in all cases. p53 staining was positive in 0% (0/10) LGSCs, 9.1% (1/11) SBTs, and 0.0% (0/12) SCAs. One LGSC case had two PIK3CA mutations (G1633A and G3149A) in both LGSC and SBT lesions, but a BRAF mutation was detected only in an LGSC lesion. These results suggest that, compared with the values in Western populations (16–54%), the KRAS mutation frequency in LGSCs/SBTs is lower and that of PIK3CA mutations in LGSCs/SBTs is much higher in Japanese populations. Therefore, the main carcinogenesis signaling pathways may be different between Japanese and Western LGSCs. Molecular therapies targeting the PIK3CA/AKT pathway may be effective in LGSCs in Japan. MDPI 2019-12-27 /pmc/articles/PMC7168240/ /pubmed/31892193 http://dx.doi.org/10.3390/diagnostics10010013 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ishibashi, Tomoka
Nakayama, Kentaro
Razia, Sultana
Ishikawa, Masako
Nakamura, Kohei
Yamashita, Hitomi
Dey, Puja
Iida, Koji
Kurioka, Hiroko
Nakayama, Satoru
Otsuki, Yoshiro
Ishikawa, Noriyoshi
Kyo, Satoru
High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title_full High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title_fullStr High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title_full_unstemmed High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title_short High Frequency of PIK3CA Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients
title_sort high frequency of pik3ca mutations in low-grade serous ovarian carcinomas of japanese patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168240/
https://www.ncbi.nlm.nih.gov/pubmed/31892193
http://dx.doi.org/10.3390/diagnostics10010013
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