Flow cytometric DNA analysis of cirrhotic liver cells in patients with hepatocellular carcinoma can provide a new prognostic factor

Ruà, Savino; Comino, Alberto; Fruttero, A; Torchio, Pierfederico; Bouzari, Hedayat; Taraglio, Stefano; Torchio, Bruno; Capussotti, Lorenzo

doi:10.1002/(sici)1097-0142(19960915)78:6<1195::aid-cncr5>3.3.co;2-3

Cited by 3 publications

(3 citation statements)

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“…The prognostic importance of the mitotic index and tumor stage is appreciated in a number of malignancies (52,53). In addition, its value is similar to that of techniques such as nuclear antigen of cell proliferation (54) or DNA analysis (55,56). In the context of HCC, there is evidence that a high mitotic index is an unfavorable prognostic indicator (24,25,57,58), as well as an independent predictor of short-term survival in patients who undergo hepatectomy with curative intent (23).…”

Section: Discussionmentioning

confidence: 93%

Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

et al. 2021

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The expression of the inositol 1,4,5-trisphosphate receptor type 3 (ITRP3) in hepatocytes is a common event in the pathogenesis of hepatocellular carcinoma (HCC), regardless of the type of underlying liver disease. However, it is not known whether ITPR3 expression in hepatocytes is involved in tumor maintenance. The aim of the present study was to determine whether there is an association between ITPR3 expression and clinical and morphological parameters using HCC samples obtained from liver explants from patients (n=53) with different etiologies of underlying chronic liver disease (CLD). ITPR3 expression, mitosis and apoptosis were analyzed in human liver samples by immunohistochemistry. Clinical and event-free survival data were combined to assess the relationship between ITPR3 and liver cancer growth in patients. RNA sequencing analysis was performed to identify apoptotic genes altered by ITPR3 expression in a liver tumor cell line. ITPR3 was highly expressed in HCC tumor cells relative to adjacent CLD tissue and healthy livers. There was an inverse correlation between ITPR3 expression and mitotic and apoptotic indices in HCC, suggesting that ITPR3 contributed to the maintenance of HCC by promoting resistance to apoptosis. This was confirmed by the upregulation of CTSB, CHOP and GADD45, genes involved in the apoptotic pathway in HCC. The expression of ITPR3 in the liver may be a promising prognostic marker of HCC

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Section: Discussionmentioning

confidence: 93%

Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

et al. 2021

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“…2). First, in HCC, diploid hepatocytes are major drivers of HCC progression, which is supported by the observation that most HCCs in rodents and patients are diploid enriched, [42][43][44] although there are important exceptions. 10 Diploid hepatocytes are sensitive to TSG LOH, and once transformed, can proliferate quickly.…”

Section: A Model For Context-specific Functions For Diploid and Polypmentioning

confidence: 97%

“…41 However, it has been well documented that HCCs in patients and rodent models are enriched with diploid hepatocytes, suggesting that diploid hepatocytes are dominant drivers of HCC and that polyploidy may actually protect the liver from tumorigenesis. [42][43][44] Recent work has identified polyploidy-specific mechanisms for HCC protection. Zhang and colleagues used a "tunable" system to modulate ploidy.…”

Section: Polyploidy In Liver Cancermentioning

confidence: 99%

Differential Roles for Diploid and Polyploid Hepatocytes in Acute and Chronic Liver Injury

Wilkinson

Duncan

2020

Semin Liver Dis

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Hepatocytes are the primary functional cells of the liver that perform essential roles in homeostasis, regeneration, and injury. Most mammalian somatic cells are diploid and contain pairs of each chromosome, but there are also polyploid cells containing additional sets of chromosomes. Hepatocytes are among the best described polyploid cells, with polyploids comprising more than 25 and 90% of the hepatocyte population in humans and mice, respectively. Cellular and molecular mechanisms that regulate hepatic polyploidy have been uncovered, and in recent years, diploid and polyploid hepatocytes have been shown to perform specialized functions. Diploid hepatocytes accelerate liver regeneration induced by resection and may accelerate compensatory regeneration after acute injury. Polyploid hepatocytes protect the liver from tumor initiation in hepatocellular carcinoma and promote adaptation to tyrosinemia-induced chronic injury. This review describes how ploidy variations influence cellular activity and presents a model for context-specific functions for diploid and polyploid hepatocytes.

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Mitotic Index Is the Best Predictive Factor for Survival of Patients with Resected Hepatocellular Carcinoma

Ouchi¹,

Sugawara²,

Ono³

et al. 2000

Dig Surg

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Background: In patients with hepatocellular carcinoma (HCC), tumor recurrence is not infrequent after resection. It is presumed that characteristics of the tumor such as cellular malignancy might influence the prognosis of the patients in association with tumor stage and radicality of the procedure. Methods: Univariate and multivariate analyses were used to retrospectively determine the clinicopathologic factors potentially related to survival in 40 patients who underwent hepatectomy for HCC. Results: In univariate analysis, tumor stage I or II, mitotic index of 4 or less/10 random high-power fields, solitary tumor, and curative resection were significantly correlated with better survival. In multivariate analysis, the mitotic index and surgical curability were independently significant variables influencing survival of patients, and the mitotic index was the best predictive factor. A highly significant correlation was found between the mitotic index and Ki-67 labeling index. Compared to tumors with a mitotic index of 4 or less, those with a mitotic index of 5 or more had a higher association with multiple tumors and advanced tumor stage, which preclude curative resection. Conclusion: Analysis of the mitotic index is quite simple, and the mitotic index could be a useful factor for predicting the long-term survival of patients with HCC following hepatic resection.

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Flow cytometric DNA analysis of cirrhotic liver cells in patients with hepatocellular carcinoma can provide a new prognostic factor

Abstract: The results of this study suggest that S-phase fraction of cirrhotic liver parenchyma may be employed as a new parameter in the prognostic evaluation of HCC patients.

Cited by 3 publications

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Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

Inositol 1,4,5‑trisphosphate receptor type 3 is involved in resistance to apoptosis and maintenance of human hepatocellular carcinoma

Differential Roles for Diploid and Polyploid Hepatocytes in Acute and Chronic Liver Injury

Mitotic Index Is the Best Predictive Factor for Survival of Patients with Resected Hepatocellular Carcinoma

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