Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features

Mami Hatano, Hidenori Ojima, Yohei Masugi, Hanako Tsujikawa, Nobuyoshi Hiraoka, Yae Kanai, Kazuaki Shimada, Masahiro Shinoda, Michiie Sakamoto

Research output: Contribution to journalArticle

Abstract

We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

Original languageEnglish
Pages (from-to)222-232
Number of pages11
JournalHuman Pathology
Volume86
DOIs
Publication statusPublished - 2019 Apr 1

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Scirrhous Adenocarcinoma
Hepatocellular Carcinoma
Catenins
Neoplasms
Stem Cells
Keratin-19
Glutamate-Ammonia Ligase
Virus Diseases
Hepatitis B virus
Recurrence
Proteins

Keywords

  • Fibrous stroma
  • Immunohistochemistry
  • Scirrhous hepatocellular carcinoma
  • Steatosis
  • Subclassification

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

@article{5f3b0c3c99b54c0d9977983f047f9f2e,
title = "Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features",
abstract = "We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31{\%}) with fibrous stroma making up ≥50{\%} of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69{\%}) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5{\%} steatotic cells (steatotic sHCC) and those with <5{\%} steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.",
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author = "Mami Hatano and Hidenori Ojima and Yohei Masugi and Hanako Tsujikawa and Nobuyoshi Hiraoka and Yae Kanai and Kazuaki Shimada and Masahiro Shinoda and Michiie Sakamoto",
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T1 - Steatotic and nonsteatotic scirrhous hepatocellular carcinomas reveal distinct clinicopathological features

AU - Hatano, Mami

AU - Ojima, Hidenori

AU - Masugi, Yohei

AU - Tsujikawa, Hanako

AU - Hiraoka, Nobuyoshi

AU - Kanai, Yae

AU - Shimada, Kazuaki

AU - Shinoda, Masahiro

AU - Sakamoto, Michiie

PY - 2019/4/1

Y1 - 2019/4/1

N2 - We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

AB - We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.

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KW - Steatosis

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