Cell cycle regulators in multiple myeloma: Prognostic implications of p53 nuclear accumulation

Giancarlo Pruneri, Nadia Carboni, Luca Baldini, Daniela Intini, Mariangela Colombi, Francesco Bertolini, Stefano Valentini, Patrick Maisonneuve, Giuseppe Viale, Antonino Neri

Research output: Contribution to journalArticle

Abstract

Multiple myeloma (MM) is characterized by a multistep process of tumorigenesis involving genes that control cell cycle progression. The prevalence and clinical implications of p53, p21, HDM-2, p27, and cyclin E immunoreactivity in MM patients, however, have not been fully elucidated. We evaluated the immunoreactivity (IR) for p53, p21, HDM-2, p27, cyclin E, and Ki-67 in bone marrow biopsies from 48 patients. In 34 (70.8%) cases, TP53 gene mutations and HDM-2 gene amplification were analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and Southern blot densitometric analyses in the corresponding bone marrow aspirates. Nineteen (39.6%) biopsy specimens exhibited ≥10% neoplastic cells immunoreactive for p53, 23 (47.9%) for p21, 28 (58.3%) for HDM-2, 29 (60.4%) for cyclin E, and 16 (33.3%) for Ki-67; 23 (47.9%) tumors had ≥50% neoplastic cells immunoreactive for p27. TP53 gene mutations in exons 5 through 8 were detected in 3 (8.8%) cases, whereas none exhibited HDM-2 gene amplification. In the cases bearing a wild-type TP53 gene, no association was found between p53 accumulation and HDM-2 or p21 IR. The same cases had been previously investigated for the presence of the t(11;14) translocation and cyclin D1 IR; interestingly, a significant inverse correlation between cyclin D1 and p27 or cyclin E IR was noted. In addition to clinical stage and Bartl's histologic stage and grade, p53 accumulation was significantly associated with survival, and it maintained its prognostic significance in a multivariate analysis adjusted for age, clinical stage, and relapse. Our data suggest that the immunohistochemical evaluation of p53 IR in bone marrow biopsies may represent an adjunct in MM patient prognostication.

Original languageEnglish
Pages (from-to)41-47
Number of pages7
JournalHuman Pathology
Volume34
Issue number1
DOIs
Publication statusPublished - Jan 1 2003

Fingerprint

Cyclin E
Multiple Myeloma
p53 Genes
Cell Cycle
Gene Amplification
Bone Marrow
Cyclin D1
Biopsy
cdc Genes
Mutation
Southern Blotting
Cell Cycle Checkpoints
Exons
Carcinogenesis
Multivariate Analysis
Recurrence
Polymerase Chain Reaction
Survival
Neoplasms

Keywords

  • Cell cycle
  • Immunohistochemistry
  • Multiple myeloma
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cell cycle regulators in multiple myeloma : Prognostic implications of p53 nuclear accumulation. / Pruneri, Giancarlo; Carboni, Nadia; Baldini, Luca; Intini, Daniela; Colombi, Mariangela; Bertolini, Francesco; Valentini, Stefano; Maisonneuve, Patrick; Viale, Giuseppe; Neri, Antonino.

In: Human Pathology, Vol. 34, No. 1, 01.01.2003, p. 41-47.

Research output: Contribution to journalArticle

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abstract = "Multiple myeloma (MM) is characterized by a multistep process of tumorigenesis involving genes that control cell cycle progression. The prevalence and clinical implications of p53, p21, HDM-2, p27, and cyclin E immunoreactivity in MM patients, however, have not been fully elucidated. We evaluated the immunoreactivity (IR) for p53, p21, HDM-2, p27, cyclin E, and Ki-67 in bone marrow biopsies from 48 patients. In 34 (70.8{\%}) cases, TP53 gene mutations and HDM-2 gene amplification were analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and Southern blot densitometric analyses in the corresponding bone marrow aspirates. Nineteen (39.6{\%}) biopsy specimens exhibited ≥10{\%} neoplastic cells immunoreactive for p53, 23 (47.9{\%}) for p21, 28 (58.3{\%}) for HDM-2, 29 (60.4{\%}) for cyclin E, and 16 (33.3{\%}) for Ki-67; 23 (47.9{\%}) tumors had ≥50{\%} neoplastic cells immunoreactive for p27. TP53 gene mutations in exons 5 through 8 were detected in 3 (8.8{\%}) cases, whereas none exhibited HDM-2 gene amplification. In the cases bearing a wild-type TP53 gene, no association was found between p53 accumulation and HDM-2 or p21 IR. The same cases had been previously investigated for the presence of the t(11;14) translocation and cyclin D1 IR; interestingly, a significant inverse correlation between cyclin D1 and p27 or cyclin E IR was noted. In addition to clinical stage and Bartl's histologic stage and grade, p53 accumulation was significantly associated with survival, and it maintained its prognostic significance in a multivariate analysis adjusted for age, clinical stage, and relapse. Our data suggest that the immunohistochemical evaluation of p53 IR in bone marrow biopsies may represent an adjunct in MM patient prognostication.",
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AU - Colombi, Mariangela

AU - Bertolini, Francesco

AU - Valentini, Stefano

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AB - Multiple myeloma (MM) is characterized by a multistep process of tumorigenesis involving genes that control cell cycle progression. The prevalence and clinical implications of p53, p21, HDM-2, p27, and cyclin E immunoreactivity in MM patients, however, have not been fully elucidated. We evaluated the immunoreactivity (IR) for p53, p21, HDM-2, p27, cyclin E, and Ki-67 in bone marrow biopsies from 48 patients. In 34 (70.8%) cases, TP53 gene mutations and HDM-2 gene amplification were analyzed by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and Southern blot densitometric analyses in the corresponding bone marrow aspirates. Nineteen (39.6%) biopsy specimens exhibited ≥10% neoplastic cells immunoreactive for p53, 23 (47.9%) for p21, 28 (58.3%) for HDM-2, 29 (60.4%) for cyclin E, and 16 (33.3%) for Ki-67; 23 (47.9%) tumors had ≥50% neoplastic cells immunoreactive for p27. TP53 gene mutations in exons 5 through 8 were detected in 3 (8.8%) cases, whereas none exhibited HDM-2 gene amplification. In the cases bearing a wild-type TP53 gene, no association was found between p53 accumulation and HDM-2 or p21 IR. The same cases had been previously investigated for the presence of the t(11;14) translocation and cyclin D1 IR; interestingly, a significant inverse correlation between cyclin D1 and p27 or cyclin E IR was noted. In addition to clinical stage and Bartl's histologic stage and grade, p53 accumulation was significantly associated with survival, and it maintained its prognostic significance in a multivariate analysis adjusted for age, clinical stage, and relapse. Our data suggest that the immunohistochemical evaluation of p53 IR in bone marrow biopsies may represent an adjunct in MM patient prognostication.

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