Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma

Fukiko Kawai-Kitahata, Yasuhiro Asahina, Shun Kaneko, Jun Tsuchiya, Ayako Sato, Masato Miyoshi, Tomoyuki Tsunoda, Emi Inoue-Shinomiya, Miyako Murakawa, Sayuri Nitta, Yasuhiro Itsui, Mina Nakagawa, Seishin Azuma, Sei Kakinuma, Minoru Tanabe, Emiko Sugawara, Akira Takemoto, Hidenori Ojima, Michiie Sakamoto, Masaru Muraoka & 4 others Shinichi Takano, Shinya Maekawa, Nobuyuki Enomoto, Mamoru Watanabe

Research output: Contribution to journalArticle

Abstract

Aim: The genetic profile of cholangiolocellular carcinoma (CLC) and its origin in relation to hepatocellular carcinoma (HCC) remain unclear. To elucidate the genetic profile of CLC, a comprehensive analysis of genetic mutations was carried out in a case of CLC with an HCC-like focal area and metachronous HCC. Method: Liver tissue was obtained from CLC, a co-existent HCC-like area, and metachronously developed HCC by laser capture microdissection of formalin-fixed paraffin-embedded specimens obtained by hepatectomy. Gene mutational profiles were analyzed comprehensively by next-generation sequencing and digital PCR. Relationships among gene profiles, immunohistochemistry, and clinicopathological findings were investigated. Results: Mutations in EGFR, PTEN, RB1, TP53, and ERBB2 were found in CLC, whereas mutations in KIT, BRAF, PTEN, TP53, and SMAD4 were found in the coexistent HCC-like area. Only the mutation in PTEN has a common Catalogue of Somatic Mutations in Cancer ID in the CLC and coexistent HCC-like area, and is related to the kinase-RAS module. In contrast, no cancer-related mutations were found in the metachronous HCC. No TERT mutations were found in any of the regions by digital PCR. Immunohistochemical staining for p53 was negative in CLC, although ≤10% positive in the coexistent HCC-like area. Immunostaining of C-kit, HER2, PTEN, and SMAD4 were negative. Conclusion: The genomic features of CLC and the focal area of an HCC-like region differ, but are related to the kinase-RAS module. The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.

Original languageEnglish
JournalHepatology Research
DOIs
Publication statusAccepted/In press - 2019 Jan 1

Fingerprint

Hepatocellular Carcinoma
Carcinoma
Mutation
Phosphotransferases
Laser Capture Microdissection
Polymerase Chain Reaction
Hepatectomy
Paraffin
Formaldehyde
Genes
Neoplasms
Carcinogenesis
Immunohistochemistry
Staining and Labeling
Liver

Keywords

  • cholangiolocellular carcinoma
  • digital polymerase chain reaction
  • gene mutation
  • hepatocellular carcinoma
  • laser capture microdissection
  • next-generation sequencing

ASJC Scopus subject areas

  • Hepatology
  • Infectious Diseases

Cite this

Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma. / Kawai-Kitahata, Fukiko; Asahina, Yasuhiro; Kaneko, Shun; Tsuchiya, Jun; Sato, Ayako; Miyoshi, Masato; Tsunoda, Tomoyuki; Inoue-Shinomiya, Emi; Murakawa, Miyako; Nitta, Sayuri; Itsui, Yasuhiro; Nakagawa, Mina; Azuma, Seishin; Kakinuma, Sei; Tanabe, Minoru; Sugawara, Emiko; Takemoto, Akira; Ojima, Hidenori; Sakamoto, Michiie; Muraoka, Masaru; Takano, Shinichi; Maekawa, Shinya; Enomoto, Nobuyuki; Watanabe, Mamoru.

In: Hepatology Research, 01.01.2019.

Research output: Contribution to journalArticle

Kawai-Kitahata, F, Asahina, Y, Kaneko, S, Tsuchiya, J, Sato, A, Miyoshi, M, Tsunoda, T, Inoue-Shinomiya, E, Murakawa, M, Nitta, S, Itsui, Y, Nakagawa, M, Azuma, S, Kakinuma, S, Tanabe, M, Sugawara, E, Takemoto, A, Ojima, H, Sakamoto, M, Muraoka, M, Takano, S, Maekawa, S, Enomoto, N & Watanabe, M 2019, 'Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma', Hepatology Research. https://doi.org/10.1111/hepr.13403
Kawai-Kitahata, Fukiko ; Asahina, Yasuhiro ; Kaneko, Shun ; Tsuchiya, Jun ; Sato, Ayako ; Miyoshi, Masato ; Tsunoda, Tomoyuki ; Inoue-Shinomiya, Emi ; Murakawa, Miyako ; Nitta, Sayuri ; Itsui, Yasuhiro ; Nakagawa, Mina ; Azuma, Seishin ; Kakinuma, Sei ; Tanabe, Minoru ; Sugawara, Emiko ; Takemoto, Akira ; Ojima, Hidenori ; Sakamoto, Michiie ; Muraoka, Masaru ; Takano, Shinichi ; Maekawa, Shinya ; Enomoto, Nobuyuki ; Watanabe, Mamoru. / Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma. In: Hepatology Research. 2019.
@article{934d6ad9eece4626be547ef79b9414c7,
title = "Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma",
abstract = "Aim: The genetic profile of cholangiolocellular carcinoma (CLC) and its origin in relation to hepatocellular carcinoma (HCC) remain unclear. To elucidate the genetic profile of CLC, a comprehensive analysis of genetic mutations was carried out in a case of CLC with an HCC-like focal area and metachronous HCC. Method: Liver tissue was obtained from CLC, a co-existent HCC-like area, and metachronously developed HCC by laser capture microdissection of formalin-fixed paraffin-embedded specimens obtained by hepatectomy. Gene mutational profiles were analyzed comprehensively by next-generation sequencing and digital PCR. Relationships among gene profiles, immunohistochemistry, and clinicopathological findings were investigated. Results: Mutations in EGFR, PTEN, RB1, TP53, and ERBB2 were found in CLC, whereas mutations in KIT, BRAF, PTEN, TP53, and SMAD4 were found in the coexistent HCC-like area. Only the mutation in PTEN has a common Catalogue of Somatic Mutations in Cancer ID in the CLC and coexistent HCC-like area, and is related to the kinase-RAS module. In contrast, no cancer-related mutations were found in the metachronous HCC. No TERT mutations were found in any of the regions by digital PCR. Immunohistochemical staining for p53 was negative in CLC, although ≤10{\%} positive in the coexistent HCC-like area. Immunostaining of C-kit, HER2, PTEN, and SMAD4 were negative. Conclusion: The genomic features of CLC and the focal area of an HCC-like region differ, but are related to the kinase-RAS module. The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.",
keywords = "cholangiolocellular carcinoma, digital polymerase chain reaction, gene mutation, hepatocellular carcinoma, laser capture microdissection, next-generation sequencing",
author = "Fukiko Kawai-Kitahata and Yasuhiro Asahina and Shun Kaneko and Jun Tsuchiya and Ayako Sato and Masato Miyoshi and Tomoyuki Tsunoda and Emi Inoue-Shinomiya and Miyako Murakawa and Sayuri Nitta and Yasuhiro Itsui and Mina Nakagawa and Seishin Azuma and Sei Kakinuma and Minoru Tanabe and Emiko Sugawara and Akira Takemoto and Hidenori Ojima and Michiie Sakamoto and Masaru Muraoka and Shinichi Takano and Shinya Maekawa and Nobuyuki Enomoto and Mamoru Watanabe",
year = "2019",
month = "1",
day = "1",
doi = "10.1111/hepr.13403",
language = "English",
journal = "Hepatology Research",
issn = "1386-6346",
publisher = "Wiley-Blackwell Publishing Ltd",

}

TY - JOUR

T1 - Comprehensive genetic analysis of cholangiolocellular carcinoma with a coexistent hepatocellular carcinoma-like area and metachronous hepatocellular carcinoma

AU - Kawai-Kitahata, Fukiko

AU - Asahina, Yasuhiro

AU - Kaneko, Shun

AU - Tsuchiya, Jun

AU - Sato, Ayako

AU - Miyoshi, Masato

AU - Tsunoda, Tomoyuki

AU - Inoue-Shinomiya, Emi

AU - Murakawa, Miyako

AU - Nitta, Sayuri

AU - Itsui, Yasuhiro

AU - Nakagawa, Mina

AU - Azuma, Seishin

AU - Kakinuma, Sei

AU - Tanabe, Minoru

AU - Sugawara, Emiko

AU - Takemoto, Akira

AU - Ojima, Hidenori

AU - Sakamoto, Michiie

AU - Muraoka, Masaru

AU - Takano, Shinichi

AU - Maekawa, Shinya

AU - Enomoto, Nobuyuki

AU - Watanabe, Mamoru

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Aim: The genetic profile of cholangiolocellular carcinoma (CLC) and its origin in relation to hepatocellular carcinoma (HCC) remain unclear. To elucidate the genetic profile of CLC, a comprehensive analysis of genetic mutations was carried out in a case of CLC with an HCC-like focal area and metachronous HCC. Method: Liver tissue was obtained from CLC, a co-existent HCC-like area, and metachronously developed HCC by laser capture microdissection of formalin-fixed paraffin-embedded specimens obtained by hepatectomy. Gene mutational profiles were analyzed comprehensively by next-generation sequencing and digital PCR. Relationships among gene profiles, immunohistochemistry, and clinicopathological findings were investigated. Results: Mutations in EGFR, PTEN, RB1, TP53, and ERBB2 were found in CLC, whereas mutations in KIT, BRAF, PTEN, TP53, and SMAD4 were found in the coexistent HCC-like area. Only the mutation in PTEN has a common Catalogue of Somatic Mutations in Cancer ID in the CLC and coexistent HCC-like area, and is related to the kinase-RAS module. In contrast, no cancer-related mutations were found in the metachronous HCC. No TERT mutations were found in any of the regions by digital PCR. Immunohistochemical staining for p53 was negative in CLC, although ≤10% positive in the coexistent HCC-like area. Immunostaining of C-kit, HER2, PTEN, and SMAD4 were negative. Conclusion: The genomic features of CLC and the focal area of an HCC-like region differ, but are related to the kinase-RAS module. The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.

AB - Aim: The genetic profile of cholangiolocellular carcinoma (CLC) and its origin in relation to hepatocellular carcinoma (HCC) remain unclear. To elucidate the genetic profile of CLC, a comprehensive analysis of genetic mutations was carried out in a case of CLC with an HCC-like focal area and metachronous HCC. Method: Liver tissue was obtained from CLC, a co-existent HCC-like area, and metachronously developed HCC by laser capture microdissection of formalin-fixed paraffin-embedded specimens obtained by hepatectomy. Gene mutational profiles were analyzed comprehensively by next-generation sequencing and digital PCR. Relationships among gene profiles, immunohistochemistry, and clinicopathological findings were investigated. Results: Mutations in EGFR, PTEN, RB1, TP53, and ERBB2 were found in CLC, whereas mutations in KIT, BRAF, PTEN, TP53, and SMAD4 were found in the coexistent HCC-like area. Only the mutation in PTEN has a common Catalogue of Somatic Mutations in Cancer ID in the CLC and coexistent HCC-like area, and is related to the kinase-RAS module. In contrast, no cancer-related mutations were found in the metachronous HCC. No TERT mutations were found in any of the regions by digital PCR. Immunohistochemical staining for p53 was negative in CLC, although ≤10% positive in the coexistent HCC-like area. Immunostaining of C-kit, HER2, PTEN, and SMAD4 were negative. Conclusion: The genomic features of CLC and the focal area of an HCC-like region differ, but are related to the kinase-RAS module. The development of carcinogenesis in the CLC and HCC-like areas in this case might differ, following a common PTEN mutation, although alteration of the kinase-RAS module is the most common molecular event in CLC.

KW - cholangiolocellular carcinoma

KW - digital polymerase chain reaction

KW - gene mutation

KW - hepatocellular carcinoma

KW - laser capture microdissection

KW - next-generation sequencing

UR - http://www.scopus.com/inward/record.url?scp=85070313548&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85070313548&partnerID=8YFLogxK

U2 - 10.1111/hepr.13403

DO - 10.1111/hepr.13403

M3 - Article

JO - Hepatology Research

JF - Hepatology Research

SN - 1386-6346

ER -