The Prognostic Significance of the Serum p53 Protein Concentration in Chinese Patients with Non-Hodgkin Lymphoma.

Authors:
Zhou M; Cen L; Chen T; Xiao R; Yang J and 2 more

Journal:
Turk J Haematol

Publication Year: 2012

DOI:
10.5505/tjh.2012.57338

PMCID:
PMC3781622

PMID:
24385725

Journal Information

Full Title: Turk J Haematol

Abbreviation: Turk J Haematol

Country: Unknown

Publisher: Unknown

Language: N/A

Publication Details

Subject Category: Hematology

Available in Europe PMC: Yes

Available in PMC: Yes

PDF Available: No

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"DISCUSSION: A number of recurrent chromosomal abnormalities associated with histopathological subtypes and clinical outcomes have been identified in NHL [6]. Translocation t(14;18) and t(8;14) are strongly associated with FL and BL, t(11;14) is associated with MCL, and t(2;5) is associated with anaplastic large-cell lymphoma, and 3q27 abnormalities are associated with DLBCL [7]. Some chromosomal aberrations are associated with significantly poor prognosis; for example, rearrangement of 8q24, +7q, and del (13q) are independently associated with significantly shorter event-free survival in DLBCL, whereas del (13q) and +7q have a similar effect in DLBCL and BL [8]. In the present study 19 of the 43 NHL patients had cytogenetic abnormalities. It is difficult to assess the prognostic significance of individual cytogenetic alterations in a small patient cohort with a short follow-up period; however, the present findings strongly support the concept that chromosomal aberrations noted at the time of diagnosis are useful for predicting the overall response rate and/or OS using univariate and multivariable analysis. : Chromosomal abnormalities were also observed in some patients with normal morphological characteristics, suggesting that bone marrow aspirate smears from a single puncture site may be of limited value in determining if the bone marrow is involved. Chromosomal analysis could be used as a supplementary technique. Another advantage of cytogenetic analysis is its ability to detect balanced translocations that would otherwise be missed by some DNAbased techniques [9]. Thus, it is necessary to perform cytogenetic examination to obtain useful information for diagnosis, staging, and prognostication. : Molecular analysis of chromosome rearrangements has resulted in identification of several genes directly implicated in the biology of NHL; however, only with cytogenetic analysis will it become possible to identify additional events that could lead to further characterization of these genetic transpositions. Studies based on chromosome painting and in situ hybridization with breakpoint-specific probes may help elucidate the nature of these complex translocations and the genes involved in the secondary events. A sequential study may also establish the relative importance of these rearrangements to different stages of the lymphoma-leukemia development process and define the roles of the additional abnormalities described herein. : The p53 gene is a cancer suppressor gene located at chromosome 17p13.1. It encodes a 53-kDa nuclear phosphoprotein (p53 protein). It acts as a negative regulator of the cell cycle [10]. It has been shown that p53 protein is activated in response to DNA damage and oncogenic stress via 2 distinct signaling pathways involving kinase-mediated phosphorylation of p53 protein by ATM/CHK2/1 cascade and inhibition of MDM2 via p19Arf, which results in p53 protein stabilization [11,12,13,14]. Solid tumors, including non-small-cell lung cancer, breast cancer, colorectal cancer, osteosarcoma, bladder cancer, and prostate cancer, exhibit increased apoptosis in response to Advexin [15]. Because serum p53 protein can be found in a small percentage of normal controls, its presence is not considered a diagnostic marker of cancer. Whether its serum concentration should be used as a screening marker or a predictive factor for the development of cancer remains to be determined. It has been reported to be variably present in the sera of patients with various malignancies. Several investigators have reported that the mean preoperative serum concentration of p53 protein in patients with head and neck squamous cell carcinoma was significantly higher than that in healthy controls. Higher serum p53 protein levels were also observed in lung cancer, pancreatic carcinoma, and colorectal cancer patients than in normal controls [16,17,18,19]. : In the present study p53 protein was observed in the sera of NHL patients, which confirmed its value as a marker of the p53 concentration in NHL. The present data show that over-expression of p53 protein (≥0.35 U/ mL) was associated with a lower CR/PR rate and poor OS. Although the following conclusion cannot be considered definitive because of the small sample size, the findings suggest that serum p53 protein may be a potential prognostic marker for NHL. Unlike staging, sex is not a conventional means of assessing disease severity, and there is no consistent concept of its role in the prognosis of NHL. The present data show that female gender was positively correlated with longer OS than male gender, but this gender difference must be investigated further by studies with larger samples. : Conflict of Interest Statement : None of the authors have any conflicts of interest, including specific financial interests, relationships, and/or affiliations, relevant to the subject matter or materials included."

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