Hyo Jeong Kang1,2, Ji-Hye Oh3, Yeon Wook Kim4, Wonkyung Kim3, Jihyun An5, Chang Ohk Sung1, Jihun Kim1,2, Ju Hyun Shim2,6, Shin Hwang2,7, Eunsil Yu1,2, Christopher M Heaphy8,9, Seung-Mo Hong1,4. 1. Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 2. Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 3. Department of Medical Science, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, Republic of Korea. 4. Asan Institute for Life Science, Asan Medical Center, Seoul, Republic of Korea. 5. Department of Gastroenterology and Hepatology, Hanyang University of Medicine, Guri, Republic of Korea. 6. Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 7. Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea. 8. Department of Medicine, Boston University School of Medicine, Boston, MA, USA. 9. Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
Abstract
BACKGROUND & AIMS: Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown. METHODS: To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC. RESULTS: Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P=0.023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P<0.001). Somatic mutations in ALT-associated genes, including ATRX, SMARCAL1, FANCG, FANCM, SP100, TSPYL5, and RAD52 were more frequent in chromophobe HCC (30.4%, 7/23 cases) compared to conventional HCC (11.8%, 21/178 cases; P=0.024). CONCLUSIONS: Chromophobe HCC is a unique subtype of HCC with a prevalence of ~10%. Compared to conventional HCC, chromophobe HCC is associated with female predominance and ALT, although overall and recurrence-free outcomes are similar to conventional HCC. This article is protected by copyright. All rights reserved.
BACKGROUND & AIMS:Chromophobe hepatocellular carcinoma (HCC) is a newly included subtype of HCC in the 5th edition of the WHO classification with distinctive histological features (chromophobic cytoplasm with anaplastic nuclei and pseudocyst formation) and is strongly associated with the alternative lengthening of telomeres (ALT) phenotype. However, the clinicopathologic characterization and molecular features of chromophobe HCC are unknown. METHODS: To comprehensively characterize chromophobe HCC, whole exome sequencing, copy number variation, and transcriptomic analyses were performed in 224 surgically resected HCC cases. Additionally, telomere-specific fluorescence in situ hybridization was used to assess ALT. These genomic profiles and ALT status were compared with clinicopathological features among subtypes of HCC, particularly chromophobe HCC and conventional HCC. RESULTS:Chromophobe HCC was observed in 10.3% (23/224) cases and, compared to conventional HCC, was more frequent in females (P=0.023). The overall and recurrence-free survival outcomes were similar between patients with chromophobe HCC and conventional HCC. However, chromophobe HCC displayed significantly more upregulated genes involving cell cycle progression and DNA repair. Additionally, ALT was significantly enriched in chromophobe HCC (87%; 20/23) compared to conventional HCC (2.2%, 4/178; P<0.001). Somatic mutations in ALT-associated genes, including ATRX, SMARCAL1, FANCG, FANCM, SP100, TSPYL5, and RAD52 were more frequent in chromophobe HCC (30.4%, 7/23 cases) compared to conventional HCC (11.8%, 21/178 cases; P=0.024). CONCLUSIONS:Chromophobe HCC is a unique subtype of HCC with a prevalence of ~10%. Compared to conventional HCC, chromophobe HCC is associated with female predominance and ALT, although overall and recurrence-free outcomes are similar to conventional HCC. This article is protected by copyright. All rights reserved.
Entities:
Keywords:
Chromophobe; Hepatocellular carcinoma; alternative lengthening of telomeres
Authors: Dina Sweed; Enas Sweed; Inas Moaz; Asmaa Mosbeh; Yahya Fayed; Sara Mohamed Abd Elhamed; Eman Sweed; Mahmoud Macshut; Shimaa Abdelsattar; Shimaa Kilany; Sara A Saied; Reda Badr; Mahmoud S Abdallah; Nermine Ehsan Journal: World J Surg Oncol Date: 2022-09-19 Impact factor: 3.253