Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas

Stefano Pepe, Angela Ruggiero, Maria D'Acquisto, Michelino De Laurentiis, Sabino De Placido, Claudia Sandomenico, Stefania Staibano, Gaetano De Rosa, Antonio Lucariello, Massimino D'Armiento, Angelo R. Bianco

Research output: Contribution to journalArticle

Abstract

BACKGROUND. p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF. METHODS. Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry. RESULTS. In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0.03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P <0.0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P <0.0001) and low SPF (P = 0.035). CONCLUSIONS. Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is Still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF. (C) 2000 American Cancer Society.

Original languageEnglish
Pages (from-to)1065-1075
Number of pages11
JournalCancer
Volume89
Issue number5
DOIs
Publication statusPublished - Sep 1 2000

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S Phase
Renal Cell Carcinoma
Ploidies
DNA
Kidney
Aneuploidy
Proteins
Carcinoma
Neoplasms
Kidney Neoplasms
Oncogene Proteins
Diploidy
Genes
Cell Cycle
Flow Cytometry
Cell Death
Immunohistochemistry
Phenotype
Mutation

Keywords

  • bcl-2
  • DNA content
  • Flow cytometry
  • Immuno-histochemistry
  • p53
  • S-phase fraction

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas. / Pepe, Stefano; Ruggiero, Angela; D'Acquisto, Maria; De Laurentiis, Michelino; De Placido, Sabino; Sandomenico, Claudia; Staibano, Stefania; De Rosa, Gaetano; Lucariello, Antonio; D'Armiento, Massimino; Bianco, Angelo R.

In: Cancer, Vol. 89, No. 5, 01.09.2000, p. 1065-1075.

Research output: Contribution to journalArticle

Pepe, Stefano ; Ruggiero, Angela ; D'Acquisto, Maria ; De Laurentiis, Michelino ; De Placido, Sabino ; Sandomenico, Claudia ; Staibano, Stefania ; De Rosa, Gaetano ; Lucariello, Antonio ; D'Armiento, Massimino ; Bianco, Angelo R. / Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas. In: Cancer. 2000 ; Vol. 89, No. 5. pp. 1065-1075.
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title = "Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas",
abstract = "BACKGROUND. p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF. METHODS. Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry. RESULTS. In our study, 4 of 32 (12.5{\%}) were found to be diploid, and 28 of 32 (87.5{\%}) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50{\%}) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6{\%}) tumors and was correlated with the more advanced Robson stage tumor (P = 0.03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P <0.0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P <0.0001) and low SPF (P = 0.035). CONCLUSIONS. Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is Still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF. (C) 2000 American Cancer Society.",
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T1 - Nuclear DNA content-derived parameters correlated with heterogeneous expression of p53 and bcl-2 proteins in clear cell renal carcinomas

AU - Pepe, Stefano

AU - Ruggiero, Angela

AU - D'Acquisto, Maria

AU - De Laurentiis, Michelino

AU - De Placido, Sabino

AU - Sandomenico, Claudia

AU - Staibano, Stefania

AU - De Rosa, Gaetano

AU - Lucariello, Antonio

AU - D'Armiento, Massimino

AU - Bianco, Angelo R.

PY - 2000/9/1

Y1 - 2000/9/1

N2 - BACKGROUND. p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF. METHODS. Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry. RESULTS. In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0.03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P <0.0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P <0.0001) and low SPF (P = 0.035). CONCLUSIONS. Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is Still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF. (C) 2000 American Cancer Society.

AB - BACKGROUND. p53 and bcl-2 are two key genes involved in cell cycle and cell death regulation. Altered expression or mutation of these genes has been found in human cancers and also has been identified in clear cell renal carcinoma (RCC). Their role in RCC progression, however, is still unclear. By contrast, the prognostic significance of ploidy and S-phase fraction (SPF) have been studied extensively in RCC. To better characterize the biologic role of p53 and bcl-2 oncoproteins in RCC, we offer a multisample correlative analysis of the expression of these two proteins with ploidy and SPF. METHODS. Ploidy and SPF along with p53 and bcl-2 expression were analyzed in 296 specimens, selected by multiple sampling of 33 consecutive operable RCCs. The expression of p53 and bcl-2 proteins was studied by immunohistochemistry, and SPF and tumor ploidy were studied by flow cytometry. RESULTS. In our study, 4 of 32 (12.5%) were found to be diploid, and 28 of 32 (87.5%) cases showed an abnormal DNA content. Among the aneuploid tumors, 14 of 28 (50%) were multiploid. Heterogeneous DNA content was detected in 21 of 32 (65.6%) tumors and was correlated with the more advanced Robson stage tumor (P = 0.03). Intratumor heterogeneity also was detected for p53 and bcl-2 protein expression. Expression of p53 protein correlated with the lack of bcl-2 protein expression (P = 0.0032), aneuploidy (P <0.0001), and high SPF (P = 0.0006), whereas bcl-2 expression was associated with a normal DNA content (P <0.0001) and low SPF (P = 0.035). CONCLUSIONS. Within each RCC, p53 and bcl-2 expression is markedly heterogeneous. Our results depicted a scenario in which bcl-2 protein, expressed by normal renal parenchyma, is Still present in euploid cell clones of RCC but disappears during the progression of renal neoplasm toward a more aggressive phenotype characterized by overexpression of p53 protein, aneuploidy, and high SPF. (C) 2000 American Cancer Society.

KW - bcl-2

KW - DNA content

KW - Flow cytometry

KW - Immuno-histochemistry

KW - p53

KW - S-phase fraction

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