Chordoma of the skull base: predictors of tumor recurrence

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  • 1 Institutes of Neurosurgery and Pathology, Catholic University School of Medicine; and Institute of Neurobiology and Molecular Medicine, National Council for Research, Rome, Italy
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Object. Chordomas of the skull base are generally regarded as slow-growing tumors; however, approximately 20% of these lesions have been shown to recur as early as 1 year postsurgery. The classic pathological paradigms are poor predictors of outcome, and additional markers are needed to identify patients at risk for early tumor recurrence. In this study the authors describe such a marker.

Methods. In a series of 26 patients with chordomas of the skull base, the authors investigated the relationship between the biological behavior of the tumor, which was determined according to the interval for its recurrence and volume doubling time, and several pathological and molecular features, which included the histological variant, proliferative activity, mutation of p53 protein, expression of human telomerase reverse transcriptase (hTERT) messenger (m)RNA, loss of heterozygosity (LOH), and microsatellite instability. The major finding in this study was that hTERT mRNA expression in chordoma cells identifies those tumors that exhibit unusually fast rates of growth. The expression of hTERT mRNA was frequently associated with mutation of p53 protein, indicating that telomerase dysfunction combines with abnormal p53 function to initiate the unrestrained clonal expansion of the tumor cells. In cases in which the tumor was partially removed, mutation of p53 protein and expression of hTERT mRNA predicted increased doubling time for residual tumor as well as the probability of tumor recurrence. Cell proliferation, as investigated using the Ki-67 method, was significantly related to the tumor doubling time; however, the authors found that the pattern of cell proliferation was not homogeneous throughout the chordoma tissue, and that the proliferative index might change by a factor as high as 8 among different regions of the same tumor. The LOH and microsatellite instability do not seem to affect the prognosis of skull base chordomas.

Conclusions. Reactivation of telomerase in chordomas is a reliable predictor of outcome. The ability to predict the biological behavior of chordomas might have immediate implications in the management of this disease in patients who undergo surgery.

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Contributor Notes

Address reprint requests to: Roberto Pallini, M.D., Department of Neurosurgery, Catholic University School of Medicine, Largo A. Gemelli 8, 00168 Rome, Italy. e-mail: pallini@rm.unicatt.it.
  • 1.

    Al-Mefty O, & Borba LAB: Skull base chordomas: a management challenge. J Neurosurg 86:182189, 1997 Al-Mefty O, Borba LAB: Skull base chordomas: a management challenge. J Neurosurg 86:182–189, 1997

    • Search Google Scholar
    • Export Citation
  • 2.

    Alvino E, , Fernandez E, & Pallini R: Microsatellite instability in primary brain tumors. Neurol Res 22:571575, 2000 Alvino E, Fernandez E, Pallini R: Microsatellite instability in primary brain tumors. Neurol Res 22:571–575, 2000

    • Search Google Scholar
    • Export Citation
  • 3.

    Arnold H, & Herrmann HD: Skull base chordoma with cavernous sinus involvement. Partial or radical tumour removal? Acta Neurochir 83:3137, 1986 Arnold H, Herrmann HD: Skull base chordoma with cavernous sinus involvement. Partial or radical tumour removal? Acta Neurochir 83:31–37, 1986

    • Search Google Scholar
    • Export Citation
  • 4.

    Benk V, , Liebsch NJ, & Munzenrider JE, et al: Base of skull and cervical spine chordomas in children treated by high-dose irradiation. Int J Radiat Oncol Biol Phys 31:577581, 1995 Benk V, Liebsch NJ, Munzenrider JE, et al: Base of skull and cervical spine chordomas in children treated by high-dose irradiation. Int J Radiat Oncol Biol Phys 31:577–581, 1995

    • Search Google Scholar
    • Export Citation
  • 5.

    Bergh P, , Kindblom LG, & Gunterberg B, et al: Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients. Cancer 88:21222134, 2000 Bergh P, Kindblom LG, Gunterberg B, et al: Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients. Cancer 88:2122–2134, 2000

    • Search Google Scholar
    • Export Citation
  • 6.

    Boland CR, , Thibodeau SN, & Hamilton SR, et al: A National Cancer Institute Workshop on Microsatellite instability for cancer detection and familiar predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:52485257, 1998 Boland CR, Thibodeau SN, Hamilton SR, et al: A National Cancer Institute Workshop on Microsatellite instability for cancer detection and familiar predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res 58:5248–5257, 1998

    • Search Google Scholar
    • Export Citation
  • 7.

    Borba L, , Al-Mefty O, & Mrak RE, et al: Cranial chordomas in children and adolescents. J Neurosurg 84:584591, 1996 Borba L, Al-Mefty O, Mrak RE, et al: Cranial chordomas in children and adolescents. J Neurosurg 84:584–591, 1996

    • Search Google Scholar
    • Export Citation
  • 8.

    Buonamici L, , Roncaroli F, & Fioravanti A, et al: Cytogenetic investigation of chordomas of the skull. Cancer Genet Cytogenet 112:4952, 1999 Buonamici L, Roncaroli F, Fioravanti A, et al: Cytogenetic investigation of chordomas of the skull. Cancer Genet Cytogenet 112:49–52, 1999

    • Search Google Scholar
    • Export Citation
  • 9.

    Burger PC, & Scheithauer BW: Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology, 1994, pp 303306 Burger PC, Scheithauer BW: Tumors of the Central Nervous System. Washington, DC: Armed Forces Institute of Pathology, 1994, pp 303–306

    • Search Google Scholar
    • Export Citation
  • 10.

    Butler MG, , Dahir GA, & Hedges LK, et al: Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas. Cancer Genet Cytogenet 85:5157, 1995 Butler MG, Dahir GA, Hedges LK, et al: Cytogenetic, telomere, and telomerase studies in five surgically managed lumbosacral chordomas. Cancer Genet Cytogenet 85:51–57, 1995

    • Search Google Scholar
    • Export Citation
  • 11.

    Colli B, & Al-Mefty O: Chordomas of the craniocervical junction: follow-up review and prognostic factors. J Neurosurg 95:933943, 2001 Colli B, Al-Mefty O: Chordomas of the craniocervical junction: follow-up review and prognostic factors. J Neurosurg 95:933–943, 2001

    • Search Google Scholar
    • Export Citation
  • 12.

    Crockard HA, , Steel T, & Plowman N, et al: A multidisciplinary team approach to skull base chordomas. J Neurosurg 95:175183, 2001 Crockard HA, Steel T, Plowman N, et al: A multidisciplinary team approach to skull base chordomas. J Neurosurg 95:175–183, 2001

    • Search Google Scholar
    • Export Citation
  • 13.

    Dietmaier W, , Wallinger S, & Bocker T, et al: Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:47494756, 1997 Dietmaier W, Wallinger S, Bocker T, et al: Diagnostic microsatellite instability: definition and correlation with mismatch repair protein expression. Cancer Res 57:4749–4756, 1997

    • Search Google Scholar
    • Export Citation
  • 14.

    Eisenberg MB, , Woloschak M, & Sen C, et al: Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas. Surg Neurol 47:156161, 1997 Eisenberg MB, Woloschak M, Sen C, et al: Loss of heterozygosity in the retinoblastoma tumor suppressor gene in skull base chordomas and chondrosarcomas. Surg Neurol 47:156–161, 1997

    • Search Google Scholar
    • Export Citation
  • 15.

    Eshlemann JR, & Markowitz SD: Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7:8389, 1995 Eshlemann JR, Markowitz SD: Microsatellite instability in inherited and sporadic neoplasms. Curr Opin Oncol 7:83–89, 1995

    • Search Google Scholar
    • Export Citation
  • 16.

    Falchetti ML, , Pallini R, & D'Ambrosio E, et al: In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme. Int J Cancer 88:895901, 2000 Falchetti ML, Pallini R, D'Ambrosio E, et al: In situ detection of telomerase catalytic subunit mRNA in glioblastoma multiforme. Int J Cancer 88:895–901, 2000

    • Search Google Scholar
    • Export Citation
  • 17.

    Falchetti ML, , Pallini R, & Larocca LM, et al: Telomerase expression in intracranial tumors: prognostic potential for malignant gliomas and meningiomas. J Clin Pathol 52:234236, 1999 Falchetti ML, Pallini R, Larocca LM, et al: Telomerase expression in intracranial tumors: prognostic potential for malignant gliomas and meningiomas. J Clin Pathol 52:234–236, 1999

    • Search Google Scholar
    • Export Citation
  • 18.

    Felsher DW, & Bishop JM: Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4:199207, 1999 Felsher DW, Bishop JM: Reversible tumorigenesis by MYC in hematopoietic lineages. Mol Cell 4:199–207, 1999

    • Search Google Scholar
    • Export Citation
  • 19.

    Fishel R, , Lescoe MK, & Rao MRS, et al: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:10271038, 1993 Fishel R, Lescoe MK, Rao MRS, et al: The human mutator gene homolog MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75:1027–1038, 1993

    • Search Google Scholar
    • Export Citation
  • 20.

    Flores ER, , Tsai KY, & Crowley D, et al: p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416:560564, 2002 Flores ER, Tsai KY, Crowley D, et al: p63 and p73 are required for p53-dependent apoptosis in response to DNA damage. Nature 416:560–564, 2002

    • Search Google Scholar
    • Export Citation
  • 21.

    Forsyth PA, , Cascino TL, & Shaw EG, et al: Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. J Neurosurg 78:741747, 1993 Forsyth PA, Cascino TL, Shaw EG, et al: Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. J Neurosurg 78:741–747, 1993

    • Search Google Scholar
    • Export Citation
  • 22.

    Gay E, , Sekhar LN, & Rubinstein E, et al: Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery 36:887897, 1995 Gay E, Sekhar LN, Rubinstein E, et al: Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery 36:887–897, 1995

    • Search Google Scholar
    • Export Citation
  • 23.

    Harada K, , Kurisu K, & Tahara H, et al: Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker. J Neurosurg 93:618625, 2000 Harada K, Kurisu K, Tahara H, et al: Telomerase activity in primary and secondary glioblastomas multiforme as a novel molecular tumor marker. J Neurosurg 93:618–625, 2000

    • Search Google Scholar
    • Export Citation
  • 24.

    Heffelfinger MJ, , Dahlin DC, & MacCarty CS, et al: Chordomas and cartilaginous tumors at the skull base. Cancer 32:410420, 1973 Heffelfinger MJ, Dahlin DC, MacCarty CS, et al: Chordomas and cartilaginous tumors at the skull base. Cancer 32:410–420, 1973

    • Search Google Scholar
    • Export Citation
  • 25.

    Holton JL, , Steel T, & Luxsuwong M, et al: Skull base chordomas: correlation of tumor doubling time with age, mitosis and Ki67 proliferation index. Neuropathol Appl Neurobiol 26:497503, 2000 Holton JL, Steel T, Luxsuwong M, et al: Skull base chordomas: correlation of tumor doubling time with age, mitosis and Ki67 proliferation index. Neuropathol Appl Neurobiol 26:497–503, 2000

    • Search Google Scholar
    • Export Citation
  • 26.

    Huettner CS, , Zhang P, & Van Etten RA, et al: Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 24:5760, 2000 Huettner CS, Zhang P, Van Etten RA, et al: Reversibility of acute B-cell leukaemia induced by BCR-ABL1. Nat Genet 24:57–60, 2000

    • Search Google Scholar
    • Export Citation
  • 27.

    Hug EB, , Loredo LN, & Slater JD, et al: Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg 91:432439, 1999 Hug EB, Loredo LN, Slater JD, et al: Proton radiation therapy for chordomas and chondrosarcomas of the skull base. J Neurosurg 91:432–439, 1999

    • Search Google Scholar
    • Export Citation
  • 28.

    Klingler L, , Shooks J, & Fiedler PN, et al: Microsatellite instability in sacral chordoma. J Surg Oncol 73:100103, 2000 Klingler L, Shooks J, Fiedler PN, et al: Microsatellite instability in sacral chordoma. J Surg Oncol 73:100–103, 2000

    • Search Google Scholar
    • Export Citation
  • 29.

    Kolquist KA, , Ellisen LW, & Counter CM, et al: Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet 19:182186, 1998 Kolquist KA, Ellisen LW, Counter CM, et al: Expression of TERT in early premalignant lesions and a subset of cells in normal tissues. Nat Genet 19:182–186, 1998

    • Search Google Scholar
    • Export Citation
  • 30.

    Leach FS, , Nicolaides NC, & Papadopoulos N, et al: Mutation of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:12151225, 1993 Leach FS, Nicolaides NC, Papadopoulos N, et al: Mutation of a mutS homolog in hereditary nonpolyposis colorectal cancer. Cell 75:1215–1225, 1993

    • Search Google Scholar
    • Export Citation
  • 31.

    Maggiano N, , Piantelli M, & Ricci R, et al: Detection of growth hormone-producing cells in human thymus by immunohistochemistry and non-radioactive in situ hybridization. J Histochem Cytochem 42:13491354, 1994 Maggiano N, Piantelli M, Ricci R, et al: Detection of growth hormone-producing cells in human thymus by immunohistochemistry and non-radioactive in situ hybridization. J Histochem Cytochem 42:1349–1354, 1994

    • Search Google Scholar
    • Export Citation
  • 32.

    Maira G, , Pallini R, & Anile C, et al: Surgical treatment of clival chordomas: the transsphenoidal approach revisited. J Neurosurg 85:784792, 1996 Maira G, Pallini R, Anile C, et al: Surgical treatment of clival chordomas: the transsphenoidal approach revisited. J Neurosurg 85:784–792, 1996

    • Search Google Scholar
    • Export Citation
  • 33.

    Matsuno A, , Sasaki T, & Nagashima T, et al: Immunohistochemical examination of proliferative potentials and the expression of cell cycle-related proteins of intracranial chordomas. Hum Pathol 28:714719, 1997 Matsuno A, Sasaki T, Nagashima T, et al: Immunohistochemical examination of proliferative potentials and the expression of cell cycle-related proteins of intracranial chordomas. Hum Pathol 28:714–719, 1997

    • Search Google Scholar
    • Export Citation
  • 34.

    Menezes AH, & Traynelis VC: Tumors of the craniovertebral junction, in Youmans JR (ed): Neurological Surgery: A Comprehensive Reference Guide to the Diagnosis and Management of Neurosurgical Problems, ed 4. Philadelphia: WB Saunders, 1996, Vol 4, pp 30413072 Menezes AH, Traynelis VC: Tumors of the craniovertebral junction, in Youmans JR (ed): Neurological Surgery: A Comprehensive Reference Guide to the Diagnosis and Management of Neurosurgical Problems, ed 4. Philadelphia: WB Saunders, 1996, Vol 4, pp 3041–3072

    • Search Google Scholar
    • Export Citation
  • 35.

    Mitchell A, , Scheithauer BW, & Unni K, et al: Chordoma and chondroid tumors of the spheno-occiput: immunohistochemical study of 41 cases. Am J Clin Pathol 98:345, 1992 (Abstract) Mitchell A, Scheithauer BW, Unni K, et al: Chordoma and chondroid tumors of the spheno-occiput: immunohistochemical study of 41 cases. Am J Clin Pathol 98:345, 1992 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 36.

    Mitchell A, , Scheithauer BW, & Unni KK, et al: Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases whit prognostic and nosologic implications. Cancer 72:29432949, 1993 Mitchell A, Scheithauer BW, Unni KK, et al: Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases whit prognostic and nosologic implications. Cancer 72:2943–2949, 1993

    • Search Google Scholar
    • Export Citation
  • 37.

    Naka T, , Fukuda T, & Chuman H, et al: Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia. Hum Pathol 27:381387, 1996 Naka T, Fukuda T, Chuman H, et al: Proliferative activities in conventional chordoma: a clinicopathologic, DNA flow cytometric, and immunohistochemical analysis of 17 specimens with special reference to anaplastic chordoma showing a diffuse proliferation and nuclear atypia. Hum Pathol 27:381–387, 1996

    • Search Google Scholar
    • Export Citation
  • 38.

    O'Connel JX, , Renard LG, & Liebsch NJ, et al: Base of skull chordomas. A correlative study of histologic and clinical features of 62 cases. Cancer 74:22612267, 1994 O'Connel JX, Renard LG, Liebsch NJ, et al: Base of skull chordomas. A correlative study of histologic and clinical features of 62 cases. Cancer 74:2261–2267, 1994

    • Search Google Scholar
    • Export Citation
  • 39.

    Pallini R, , Pierconti F, & Falchetti ML, et al: Evidence for telomerase involvement in the angiogenesis of astrocytic tumors: expression of human telomerase reverse transcriptase messenger RNA by vascular endothelial cells. J Neurosurg 94:961971, 2001 Pallini R, Pierconti F, Falchetti ML, et al: Evidence for telomerase involvement in the angiogenesis of astrocytic tumors: expression of human telomerase reverse transcriptase messenger RNA by vascular endothelial cells. J Neurosurg 94:961–971, 2001

    • Search Google Scholar
    • Export Citation
  • 40.

    Pallini R, , Tancredi A, & Casalbore P, et al: Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by concurrent adjacent meningioma: possible role of growth factors. Case report. J Neurosurg 89:149154, 1998 Pallini R, Tancredi A, Casalbore P, et al: Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by concurrent adjacent meningioma: possible role of growth factors. Case report. J Neurosurg 89:149–154 , 1998

    • Search Google Scholar
    • Export Citation
  • 41.

    Peltomaki P, & de la Chapelle A: Mutation predisposing to hereditary nonpolyposis colorectal cancer. Adv Cancer Res 71:93119, 1997 Peltomaki P, de la Chapelle A: Mutation predisposing to hereditary nonpolyposis colorectal cancer. Adv Cancer Res 71:93–119, 1997

    • Search Google Scholar
    • Export Citation
  • 42.

    Raffel C, , Wright DC, & Gutin PH, et al: Cranial chordomas: clinical presentation and result of operative and radiation therapy in twenty-six patients. Neurosurgery 17:703710, 1985 Raffel C, Wright DC, Gutin PH, et al: Cranial chordomas: clinical presentation and result of operative and radiation therapy in twenty-six patients. Neurosurgery 17:703–710, 1985

    • Search Google Scholar
    • Export Citation
  • 43.

    Rich TA, , Schiller A, & Suit HD, et al: Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182187, 1985 Rich TA, Schiller A, Suit HD, et al: Clinical and pathologic review of 48 cases of chordoma. Cancer 56:182–187, 1985

    • Search Google Scholar
    • Export Citation
  • 44.

    Schoedel K, , Martinez AJ, & Mahoney TM, et al: Chordomas: pathological features, ploidy and silver nucleolar organizing region analysis. A study of 36 cases. Acta Neuropathol 89:139143, 1995 Schoedel K, Martinez AJ, Mahoney TM, et al: Chordomas: pathological features, ploidy and silver nucleolar organizing region analysis. A study of 36 cases. Acta Neuropathol 89:139–143, 1995

    • Search Google Scholar
    • Export Citation
  • 45.

    Sekhar LN, , Gay E, & Wright DC: Chordomas and chondrosarcomas of the cranial base, in Wilkins RH, & Rengachary SS (eds): Neurosurgery, ed 2. New York: McGraw-Hill, 1996, Vol 2, pp 15291543 Sekhar LN, Gay E, Wright DC: Chordomas and chondrosarcomas of the cranial base, in Wilkins RH, Rengachary SS (eds): Neurosurgery, ed 2. New York: McGraw-Hill, 1996, Vol 2, pp 1529–1543

    • Search Google Scholar
    • Export Citation
  • 46.

    Sen CN, , Sekhar LN, & Schramm VL, et al: Chordoma and chondrosarcoma of the cranial base: an 8-year experience. Neurosurgery 25:931941, 1989 Sen CN, Sekhar LN, Schramm VL, et al: Chordoma and chondrosarcoma of the cranial base: an 8-year experience. Neurosurgery 25:931–941, 1989

    • Search Google Scholar
    • Export Citation
  • 47.

    Shay JW, & Bacchetti S: A survey of telomerase activity in human cancer. Eur J Cancer 33:787791, 1997 Shay JW, Bacchetti S: A survey of telomerase activity in human cancer. Eur J Cancer 33:787–791, 1997

    • Search Google Scholar
    • Export Citation
  • 48.

    Thibodeau SN, , Bren G, & Shaid D: Microsatellite instability in cancer of the proximal colon. Science 260:816819, 1993 Thibodeau SN, Bren G, Shaid D: Microsatellite instability in cancer of the proximal colon. Science 260:816–819, 1993

    • Search Google Scholar
    • Export Citation
  • 49.

    Tomlinson FH, , Scheithauer BW, & Forsythe PA, et al: Sarcomatous transformation in cranial chordoma. Neurosurgery 31:1318, 1992 Tomlinson FH, Scheithauer BW, Forsythe PA, et al: Sarcomatous transformation in cranial chordoma. Neurosurgery 31:13–18, 1992

    • Search Google Scholar
    • Export Citation
  • 50.

    Vojtesek B, , Bartek J, & Midgley CA, et al: An immunochemical analysis of the human nuclear phosphoprotein p53: new monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151:237244, 1992 Vojtesek B, Bartek J, Midgley CA, et al: An immunochemical analysis of the human nuclear phosphoprotein p53: new monoclonal antibodies and epitope mapping using recombinant p53. J Immunol Methods 151:237–244, 1992

    • Search Google Scholar
    • Export Citation
  • 51.

    Watkins L, , Khudados ES, & Kaleoglu M, et al: Skull base chordomas: a review of 38 patients, 1958–88. Br J Neurosurg 7:241248, 1993 Watkins L, Khudados ES, Kaleoglu M, et al: Skull base chordomas: a review of 38 patients, 1958–88. Br J Neurosurg 7:241–248, 1993

    • Search Google Scholar
    • Export Citation
  • 52.

    Wold LE, & Laws ER Jr: Cranial chordomas in children and young adults. J Neurosurg 59:10431047, 1983 Wold LE, Laws ER Jr: Cranial chordomas in children and young adults. J Neurosurg 59:1043–1047, 1983

    • Search Google Scholar
    • Export Citation
  • 53.

    Zambetti GP, & Levine AJ: A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855865, 1993 Zambetti GP, Levine AJ: A comparison of the biological activities of wild-type and mutant p53. FASEB J 7:855–865, 1993

    • Search Google Scholar
    • Export Citation

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