Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients

Abstract Background Nuclear changes are typical in the carcinogenesis of hepatocellular carcinoma (HCC). Morphometry and chromatin texture analysis are quantitative methods for their quantification. In this study, we analyzed nuclear morphometry and chromatin texture parameters in samples of hepatoc...

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Main Authors: Jordan Boeira dos Santos, Rodrigo Tzovenos Starosta, Emily Ferreira Salles Pilar, Jefferson Daniel Kunz, Joelson Tomedi, Carlos Thadeu Schmidt Cerski, Rúbia Denise Ruppenthal
Format: Article
Language:English
Published: BMC 2022-04-01
Series:BMC Gastroenterology
Subjects:
Online Access:https://doi.org/10.1186/s12876-022-02262-5
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author Jordan Boeira dos Santos
Rodrigo Tzovenos Starosta
Emily Ferreira Salles Pilar
Jefferson Daniel Kunz
Joelson Tomedi
Carlos Thadeu Schmidt Cerski
Rúbia Denise Ruppenthal
author_facet Jordan Boeira dos Santos
Rodrigo Tzovenos Starosta
Emily Ferreira Salles Pilar
Jefferson Daniel Kunz
Joelson Tomedi
Carlos Thadeu Schmidt Cerski
Rúbia Denise Ruppenthal
author_sort Jordan Boeira dos Santos
collection DOAJ
description Abstract Background Nuclear changes are typical in the carcinogenesis of hepatocellular carcinoma (HCC). Morphometry and chromatin texture analysis are quantitative methods for their quantification. In this study, we analyzed nuclear morphometry and chromatin texture parameters in samples of hepatocellular carcinoma from liver transplant patients and their associations with clinicopathologic variables. Methods Samples of HCC and adjacent tissue from 34 individuals were collected in tissue microarray blocks. Stained slides were microphotographed using an optical microscope and nuclear parameters analyzed in ImageJ (FracLac plug-in). ROC curve analysis was used to find accurate cut-offs for differentiation of neoplastic and non-neoplastic cells. The inter-rater agreement was also evaluated. Results Nuclear morphometric and textural differences were observed between the samples of HCC and adjacent tissue of liver transplant patients. Lower mean gray value (p = 0.034) and Feret diameter (p = 0.024) were associated with higher Model for End-Stage Liver Disease (MELD) scores. Nuclei with larger area (p = 0.014) and larger Feret diameter (p = 0.035) were associated with lower survival. Lower aspect ratio was associated with HCC recurrence after the transplant (p = 0.048). The cut-off of 1.13 μm (p =  < 0.001) for aspect ratio and cut-off of 21.15 μm (p = 0.038) for perimeter were established for the differentiation of neoplastic and non-neoplastic cells. The morphometric analysis was reproducible to area, circularity, Feret diameter, mean gray value and aspect ratio between observers (p =  < 0.001). Conclusions Nuclear morphometric differences between the HCC and the adjacent tissue samples were associated with prognostic variables (MELD scores, recurrence and survival) and may predict liver transplant patients’ outcomes.
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spelling doaj.art-164b9624a8e6465d9172c95609b76b592022-12-22T00:10:33ZengBMCBMC Gastroenterology1471-230X2022-04-012211910.1186/s12876-022-02262-5Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patientsJordan Boeira dos Santos0Rodrigo Tzovenos Starosta1Emily Ferreira Salles Pilar2Jefferson Daniel Kunz3Joelson Tomedi4Carlos Thadeu Schmidt Cerski5Rúbia Denise Ruppenthal6Graduate Program in Science in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do SulDepartment of Pediatrics, Saint Louis Children’s Hospital, Washington UniversityExperimental Research Center, Hospital de Clínicas de Porto AlegreExperimental Research Center, Hospital de Clínicas de Porto AlegreDepartment of Surgical Pathology, Hospital de Clínicas de Porto AlegreGraduate Program in Science in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do SulGraduate Program in Science in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do SulAbstract Background Nuclear changes are typical in the carcinogenesis of hepatocellular carcinoma (HCC). Morphometry and chromatin texture analysis are quantitative methods for their quantification. In this study, we analyzed nuclear morphometry and chromatin texture parameters in samples of hepatocellular carcinoma from liver transplant patients and their associations with clinicopathologic variables. Methods Samples of HCC and adjacent tissue from 34 individuals were collected in tissue microarray blocks. Stained slides were microphotographed using an optical microscope and nuclear parameters analyzed in ImageJ (FracLac plug-in). ROC curve analysis was used to find accurate cut-offs for differentiation of neoplastic and non-neoplastic cells. The inter-rater agreement was also evaluated. Results Nuclear morphometric and textural differences were observed between the samples of HCC and adjacent tissue of liver transplant patients. Lower mean gray value (p = 0.034) and Feret diameter (p = 0.024) were associated with higher Model for End-Stage Liver Disease (MELD) scores. Nuclei with larger area (p = 0.014) and larger Feret diameter (p = 0.035) were associated with lower survival. Lower aspect ratio was associated with HCC recurrence after the transplant (p = 0.048). The cut-off of 1.13 μm (p =  < 0.001) for aspect ratio and cut-off of 21.15 μm (p = 0.038) for perimeter were established for the differentiation of neoplastic and non-neoplastic cells. The morphometric analysis was reproducible to area, circularity, Feret diameter, mean gray value and aspect ratio between observers (p =  < 0.001). Conclusions Nuclear morphometric differences between the HCC and the adjacent tissue samples were associated with prognostic variables (MELD scores, recurrence and survival) and may predict liver transplant patients’ outcomes.https://doi.org/10.1186/s12876-022-02262-5Hepatocellular carcinomaMorphometryChromatin textureLiver transplant
spellingShingle Jordan Boeira dos Santos
Rodrigo Tzovenos Starosta
Emily Ferreira Salles Pilar
Jefferson Daniel Kunz
Joelson Tomedi
Carlos Thadeu Schmidt Cerski
Rúbia Denise Ruppenthal
Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
BMC Gastroenterology
Hepatocellular carcinoma
Morphometry
Chromatin texture
Liver transplant
title Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
title_full Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
title_fullStr Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
title_full_unstemmed Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
title_short Nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
title_sort nuclear morphometry and chromatin texture changes in hepatocellular carcinoma samples may predict outcomes of liver transplanted patients
topic Hepatocellular carcinoma
Morphometry
Chromatin texture
Liver transplant
url https://doi.org/10.1186/s12876-022-02262-5
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