Abstract
Apoptosis pathways are known to be involved in the pathogenesis of peripheral T-cell lymphomas (PTCLs). As such, the current study attempted to investigate the overexpression of Bcl-2, Bax, or p53 with respect to the progression of PTCL. Paraffin-embedded specimens from 74 patients were analyzed immunohistochemically for Bcl-2, Bax, or p53 overexpression including PTCL-unspecified (n=45), extranodal natural killer cell/T-cell lymphoma (n=10), angioimmunoblastic T-cell lymphoma (n=7), anaplastic large cell lymphoma (n=7), and cutaneous T-cell lymphoma (n=5). The Bcl-2 overexpression was exhibited in 33 (45%), Bax, 17 (23%), and p53, 33 patients (45%). Bcl-2 overexpression was strongly associated with advanced stage (p=0.021) and higher international prognostic indices (IPI) (p=0.038). Bcl-2+/p53+ group was found to be associated with advanced stage (p=0.008) and higher IPI (p=0.001), compared with the other groups. The independent expression of Bcl-2 or p53 was not correlated with survival. Meanwhile, when confined to Bcl-2 overexpressing groups, p53 overexpression was significantly associated with poor survival (p=0.05), as the 3-year OS rate was 82.5% for Bcl-2+/p53- cases, yet only 32.9% for Bcl-2+/p53+ cases. Multivariate analyses for OS found the Bcl-2/p53 co-expression (p=0.004) as independent prognostic factor, together with advanced stage (p<0.001) and higher prognostic index for PTCL (p=0.008). Bcl-2 overexpression seemed to correlate with the progression of PTCL interacting with a p53-dependent pathway.
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References
Lowe SW, Lin AW (2000) Apoptosis in cancer. Carcinogenesis 21:485–495
Chen-Levy Z, Nourse J, Cleary ML (1989) The bcl-2 candidate proto-oncogene product is a 24-kilodalton integral-membrane protein highly expressed in lymphoid cell lines and lymphomas carrying the t(14;18) translocation. Mol Cell Biol 9:701–710
Aisenberg AC, Wilkes BM, Jacobson JO (1988) The bcl-2 gene is rearranged in many diffuse B-cell lymphomas. Blood 71:969–972
Raghoebier S, van Krieken JH, Kluin-Nelemans JC, Gillis A, van Ommen GJ, Ginsberg AM, Raffeld M, Kluin PM (1991) Oncogene rearrangements in chronic B-cell leukemia. Blood 77:1560–1564
Aguilar-Santelises M, Rottenberg ME, Lewin N, Mellstedt H, Jondal M (1996) Bcl-2, Bax and p53 expression in B-CLL in relation to in vitro survival and clinical progression. Int J Cancer 69:114–119
Reed JC, Miyashita T, Takayama S, Wang HG, Sato T, Krajewski S, Aime-Sempe C, Bodrug S, Kitada S, Hanada M (1996) BCL-2 family proteins: regulators of cell death involved in the pathogenesis of cancer and resistance to therapy. J Cell Biochem 60:23–32
Wang Y, Okan I, Szekely L, Klein G, Wiman KG (1995) bcl-2 inhibits wild-type p53-triggered apoptosis but not G1 cell cycle arrest and transactivation of WAF1 and bax. Cell Growth Differ 6:1071–1075
Chiou SK, Rao L, White E (1994) Bcl-2 blocks p53-dependent apoptosis. Mol Cell Biol 14:2556–2563
Rassidakis GZ, Jones D, Lai R, Ramalingam P, Sarris AH, McDonnell TJ, Medeiros LJ (2003) BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation. J Pathol 200:240–248
Pescarmona E, Pignoloni P, Puopolo M, Martelli M, Addesso M, Guglielmi C, Baroni CD (2001) p53 over-expression identifies a subset of nodal peripheral T-cell lymphomas with a distinctive biological profile and poor clinical outcome. J Pathol 195:361–366
Gascoyne RD, Krajewska M, Krajewski S, Connors JM, Reed JC (1997) Prognostic significance of Bax protein expression in diffuse aggressive non-Hodgkin’s lymphoma. Blood 90:3173–3178
Gascoyne RD, Adomat SA, Krajewski S, Krajewska M, Horsman DE, Tolcher AW, O'Reilly SE, Hoskins P, Coldman AJ, Reed JC, Connors JM (1997) Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. Blood 90:244–251
Sohn SK, Jung JT, Kim DH, Kim JG, Kwak EK, Park T, Shin DG, Sohn KR, Lee KB (2003) Prognostic significance of bcl-2, bax, and p53 expression in diffuse large B-cell lymphoma. Am J Hematol 73:101–107
Harris NL, Jaffe ES, Diebold J, Flandrin G, Muller-Hermelink HK, Vardiman J, Lister TA, Bloomfield CD (1999) World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting, Airlie House, Virginia, November 1997. J Clin Oncol 17:3835–3849
Gallamini A, Stelitano C, Calvi R, Bellei M, Mattei D, Vitolo U, Morabito F, Martelli M, Brusamolino E, Iannitto E, Zaja F, Cortelazzo S, Rigacci L, Devizzi L, Todeschini G, Santini G, Brugiatelli M, Federico M (2004) Peripheral T-cell lymphoma unspecified (PTCL-U): a new prognostic model from a retrospective multicentric clinical study. Blood 103:2474–2479
Hermine O, Haioun C, Lepage E, d’Agay MF, Briere J, Lavignac C, Fillet G, Salles G, Marolleau JP, Diebold J, Reyas F, Gaulard P (1996) Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l’Adulte (GELA). Blood 87:265–272
Kramer MH, Hermans J, Wijburg E, Philippo K, Geelen E, van Krieken JH, de Jong D, Maartense E, Schuuring E, Kluin PM (1998) Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood 92:3152–3162
ten Berge RL, Meijer CJ, Dukers DF, Kummer JA, Bladergroen BA, Vos W, Hack CE, Ossenkoppele GJ, Oudejans JJ (2002) Expression levels of apoptosis-related proteins predict clinical outcome in anaplastic large cell lymphoma. Blood 99:4540–4546
Villalva C, Bougrine F, Delsol G, Brousset P (2001) Bcl-2 expression in anaplastic large cell lymphoma. Am J Pathol 158:1889–1890
Nevala H, Karenko L, Vakeva L, Ranki A (2001) Proapoptotic and antiapoptotic markers in cutaneous T-cell lymphoma skin infiltrates and lymphomatoid papulosis. Br J Dermatol 145:928–937
Osada M, Ishioka C, Ichinohasama R, Kadowaki I, Murakawa Y, Watanabe M, Kanamaru R, Ikawa S (1999) Influence of p53 mutation on pathological grade, but not prognosis of non-Hodgkin's lymphoma. Anticancer Drug Dis 14:107–114
Kramer MH, Hermans J, Parker J, Krol AD, Kluin-Nelemans JC, Haak HL, van Groningen K, van Krieken JH, de Jong D, Kluin PM (1996) Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study. J Clin Oncol 14:2131–2138
Korkolopoulou P, Angelopoulou MK, Kontopidou F, Tsenga A, Patsouris E, Thomas-Tsagli E, Kittas C, Pangalis GA (1998) Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas: a multivariate survival analysis including Ki67 and p53 oncoprotein expression. Histopathology 33:240–247
Ichikawa A, Hotta T, Saito H (1993) Mutations of the p53 gene in B-cell lymphoma. Leuk Lymphoma 11:21–25
Piris MA, Pezzella F, Martinez-Montero JC, Orradre JL, Villuendas R, Sanchez-Beato M, Cuena R, Cruz MA, Martinez B, Pezella F, et al. (1994) p53 and bcl-2 expression in high-grade B-cell lymphomas: correlation with survival time. Br J Cancer 69:337–341
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Jung, J.T., Kim, D.H., Kwak, E.K. et al. Clinical role of Bcl-2, Bax, or p53 overexpression in peripheral T-cell lymphomas. Ann Hematol 85, 575–581 (2006). https://doi.org/10.1007/s00277-006-0127-z
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DOI: https://doi.org/10.1007/s00277-006-0127-z