Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential

F. Barbisan, R. Mazzucchelli, A. Santinelli, D. Stramazzotti, M. Scarpelli, A. Lopez-Beltran, Liang Cheng, Rodolfo Montironi

Research output: Contribution to journalArticle

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Abstract

A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

Original languageEnglish
Pages (from-to)615-623
Number of pages9
JournalInternational Journal of Immunopathology and Pharmacology
Volume21
Issue number3
StatePublished - Jul 2008

Fingerprint

DNA Methylation
Acetylation
Histones
Urothelium
Neoplasms
Chromatin
Carcinoma
Cell Nucleus
Karyometry
5-Methylcytosine
Epigenomics
Lysine
Immunohistochemistry
Recurrence
Muscles

Keywords

  • Global DNA methylation
  • Global histone acetylation
  • Papillary urothelial neoplasm of low malignant potential
  • Recurrence
  • Urothelium

ASJC Scopus subject areas

  • Pharmacology
  • Immunology
  • Immunology and Allergy

Cite this

Barbisan, F., Mazzucchelli, R., Santinelli, A., Stramazzotti, D., Scarpelli, M., Lopez-Beltran, A., ... Montironi, R. (2008). Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential. International Journal of Immunopathology and Pharmacology, 21(3), 615-623.

Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential. / Barbisan, F.; Mazzucchelli, R.; Santinelli, A.; Stramazzotti, D.; Scarpelli, M.; Lopez-Beltran, A.; Cheng, Liang; Montironi, Rodolfo.

In: International Journal of Immunopathology and Pharmacology, Vol. 21, No. 3, 07.2008, p. 615-623.

Research output: Contribution to journalArticle

Barbisan, F, Mazzucchelli, R, Santinelli, A, Stramazzotti, D, Scarpelli, M, Lopez-Beltran, A, Cheng, L & Montironi, R 2008, 'Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential', International Journal of Immunopathology and Pharmacology, vol. 21, no. 3, pp. 615-623.
Barbisan, F. ; Mazzucchelli, R. ; Santinelli, A. ; Stramazzotti, D. ; Scarpelli, M. ; Lopez-Beltran, A. ; Cheng, Liang ; Montironi, Rodolfo. / Immunohistochemical evaluation of global DNA methylation and histone acetylation in papillary urothelial neoplasm of low malignant potential. In: International Journal of Immunopathology and Pharmacology. 2008 ; Vol. 21, No. 3. pp. 615-623.
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abstract = "A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79{\%}) through non-recurrent and recurrent PUNLMP (86{\%} and 93{\%}, respectively) to UC (97{\%}). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90{\%}) and lowest in recurrent PUNLMP (i.e. 81{\%}). In NU and UC the mean percentages of positive nuclei were 84{\%} and 86{\%}, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.",
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AU - Stramazzotti, D.

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N2 - A preceding study has shown that karyometry detected subvisual differences in chromatin organization status between non-recurrent and recurrent papillary urothelial neoplasm of low malignant potential (PUNLMP). The status of chromatin organization depends on epigenetic events, such as DNA methylation and histone acetylation. The aim of this study is to explore global DNA methylation and global histone acetylation in non-recurrent and recurrent PUNLMP. 5-methylcytosine (5MeC) and acetylated histone H3 lysine 9 (AcH3K9) were investigated by immunohistochemistry (IHC) in 20 PUNLMP cases (10 non-recurrent and 10 recurrent), in 5 cases of normal urothelium (NU) and in 5 cases of muscle invasive pT2 urothelial carcinoma (UC). For global DNA methylation, the mean percentage of positive nuclei in the cells adjacent to the stroma increased from NU (79%) through non-recurrent and recurrent PUNLMP (86% and 93%, respectively) to UC (97%). The percentages of positive nuclei in the intermediate cell layers and in the superficial cells in the four groups were similar to those adjacent to the stroma. The proportion of nuclei with weak-to-moderate intensity was far greater than that of those strongly stained and increased steadily from NU to UC. For global histone acetylation, the mean percentage of positive nuclei was highest in non-recurrent PUNLMP (i.e. 90%) and lowest in recurrent PUNLMP (i.e. 81%). In NU and UC the mean percentages of positive nuclei were 84% and 86%, respectively. The percentage of positive nuclei decreased from the cell layer adjacent to the stroma to the superficial cell layer. The proportion of nuclei with weak-to-moderate intensity was slightly greater than that of those strongly stained. In comparison with global DNA methylation, the proportion of strongly stained nuclei was much higher. In conclusion, there are differences in global DNA methylation and histone acetylation patterns between non-recurrent and recurrent PUNLMP. Further studies are needed to elucidate the complex interplay between chromatin structure, its modifications and recurrence of PUNLMP.

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