Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus: Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation

Yoshifumi Baba, Takatsugu Ishimoto, Kazuto Harada, Keisuke Kosumi, Asuka Murata, Keisuke Miyake, Yukiharu Hiyoshi, Junji Kurashige, Masaaki Iwatsuki, Shiro Iwagami, Yuji Miyamoto, Yasuo Sakamoto, Naoya Yoshida, Eiji Oki, Ken ichi Iyama, Masayuki Watanabe, Hideo Baba

Research output: Contribution to journalArticle

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Abstract

Background: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC. Methods: A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing. Results: Of 502 tumors, 22 (4.4 %) were pathologically diagnosed as BSCC, and 440 (87 %) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 % of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001). Conclusions: These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.

Original languageEnglish
Pages (from-to)3659-3665
Number of pages7
JournalAnnals of Surgical Oncology
Volume22
Issue number11
DOIs
Publication statusPublished - Oct 15 2015

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Long Interspersed Nucleotide Elements
Methylation
Esophagus
Squamous Cell Carcinoma
Mutation
Epigenomics
Neoplasms
DNA Methylation
Esophageal Neoplasms

All Science Journal Classification (ASJC) codes

  • Surgery
  • Oncology

Cite this

Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus : Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation. / Baba, Yoshifumi; Ishimoto, Takatsugu; Harada, Kazuto; Kosumi, Keisuke; Murata, Asuka; Miyake, Keisuke; Hiyoshi, Yukiharu; Kurashige, Junji; Iwatsuki, Masaaki; Iwagami, Shiro; Miyamoto, Yuji; Sakamoto, Yasuo; Yoshida, Naoya; Oki, Eiji; Iyama, Ken ichi; Watanabe, Masayuki; Baba, Hideo.

In: Annals of Surgical Oncology, Vol. 22, No. 11, 15.10.2015, p. 3659-3665.

Research output: Contribution to journalArticle

Baba, Y, Ishimoto, T, Harada, K, Kosumi, K, Murata, A, Miyake, K, Hiyoshi, Y, Kurashige, J, Iwatsuki, M, Iwagami, S, Miyamoto, Y, Sakamoto, Y, Yoshida, N, Oki, E, Iyama, KI, Watanabe, M & Baba, H 2015, 'Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus: Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation', Annals of Surgical Oncology, vol. 22, no. 11, pp. 3659-3665. https://doi.org/10.1245/s10434-015-4445-z
Baba, Yoshifumi ; Ishimoto, Takatsugu ; Harada, Kazuto ; Kosumi, Keisuke ; Murata, Asuka ; Miyake, Keisuke ; Hiyoshi, Yukiharu ; Kurashige, Junji ; Iwatsuki, Masaaki ; Iwagami, Shiro ; Miyamoto, Yuji ; Sakamoto, Yasuo ; Yoshida, Naoya ; Oki, Eiji ; Iyama, Ken ichi ; Watanabe, Masayuki ; Baba, Hideo. / Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus : Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation. In: Annals of Surgical Oncology. 2015 ; Vol. 22, No. 11. pp. 3659-3665.
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title = "Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus: Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation",
abstract = "Background: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC. Methods: A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing. Results: Of 502 tumors, 22 (4.4 {\%}) were pathologically diagnosed as BSCC, and 440 (87 {\%}) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 {\%} of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001). Conclusions: These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.",
author = "Yoshifumi Baba and Takatsugu Ishimoto and Kazuto Harada and Keisuke Kosumi and Asuka Murata and Keisuke Miyake and Yukiharu Hiyoshi and Junji Kurashige and Masaaki Iwatsuki and Shiro Iwagami and Yuji Miyamoto and Yasuo Sakamoto and Naoya Yoshida and Eiji Oki and Iyama, {Ken ichi} and Masayuki Watanabe and Hideo Baba",
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T1 - Molecular Characteristics of Basaloid Squamous Cell Carcinoma of the Esophagus

T2 - Analysis of KRAS, BRAF, and PIK3CA Mutations and LINE-1 Methylation

AU - Baba, Yoshifumi

AU - Ishimoto, Takatsugu

AU - Harada, Kazuto

AU - Kosumi, Keisuke

AU - Murata, Asuka

AU - Miyake, Keisuke

AU - Hiyoshi, Yukiharu

AU - Kurashige, Junji

AU - Iwatsuki, Masaaki

AU - Iwagami, Shiro

AU - Miyamoto, Yuji

AU - Sakamoto, Yasuo

AU - Yoshida, Naoya

AU - Oki, Eiji

AU - Iyama, Ken ichi

AU - Watanabe, Masayuki

AU - Baba, Hideo

PY - 2015/10/15

Y1 - 2015/10/15

N2 - Background: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC. Methods: A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing. Results: Of 502 tumors, 22 (4.4 %) were pathologically diagnosed as BSCC, and 440 (87 %) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 % of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001). Conclusions: These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.

AB - Background: Basaloid squamous cell carcinoma (BSCC) of the esophagus is a rare carcinoma with distinct characteristics, and was recently recognized as a variant of squamous cell carcinoma (SCC). We previously revealed genetic and epigenetic alterations associated with esophageal SCCs in relation to clinical outcome, including mutations in KRAS, BRAF, and PIK3CA, p53 expression, and long interspersed nucleotide element-1 (LINE-1) methylation, a surrogate marker for global DNA methylation level. In this study, we explored these features in BSCC. Methods: A database of 502 esophageal cancers was used to evaluate the clinical and molecular characteristics of BSCC. KRAS, BRAF, and PIK3CA mutations and LINE-1 methylation were analyzed by pyrosequencing. Results: Of 502 tumors, 22 (4.4 %) were pathologically diagnosed as BSCC, and 440 (87 %) as SCC. No prognostic differences between BSCC and SCC cases were identified (p = 0.41). KRAS or BRAF mutations were not observed in BSCCs. While 23 % of SCC tumors harbored a PIK3CA mutation, all BSCC cases were wild-type for PIK3CA (p = 0.002), and there were no differences in p53 expression between BSCCs and SCCs (p = 0.57), as assessed by immunohistochemistry. Furthermore, BSCC tissues exhibited significantly lower levels of LINE-1 methylation than SCC tissues (p < 0.0001). Conclusions: These findings imply that esophageal BSCC and SCC retain different cellular phenotypes with distinct genetic and epigenetic alterations; thus, tailored therapeutic strategies should be developed against each cancer type.

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