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p53 and MIB-1 Immunohistochemistry as Predictors of the Clinical Behavior of Nonfunctioning Pituitary Adenomas

Published online by Cambridge University Press:  02 December 2014

Stephen J. Hentschel ,
Ian E. McCutcheon ,
Wayne Moore  and
Felix A. Durity
Stephen J. Hentschel
Affiliation:
Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada Department of Neurosurgery, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
Ian E. McCutcheon
Affiliation:
Department of Neurosurgery, University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA
Wayne Moore
Affiliation:
Division of Neuropathology, Department of Pathology and Laboratory Medicine, Vancouver Hospital and Health Sciences Centre, University of British Columbia, Vancouver, BC, Canada
Felix A. Durity
Affiliation:
Division of Neurosurgery, Department of Surgery, University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, BC, Canada
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Abstract:

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Background:

P53 expression and increased MIB-1 proliferation index have been shown to correlate with invasive behavior in pituitary adenomas. The purpose of this study was to determine whether these indices could be used to predict a higher likelihood of recurrence in clinically nonfunctional pituitary adenomas and thus guide adjuvant therapy.

Methods:

Fifty-one clinically nonfunctional pituitary adenomas were selected from the database at the Vancouver Hospital and Health Sciences Center between the years 1990-1998. Included were 32 nonrecurrent and 19 recurrent adenomas.

Results:

The mean initial labelling index for p53 in nonrecurrent tumours was 0.38% (0-1.58%), while it was 0.46% (0-3.65%) for recurrent adenomas. The mean initial MIB-1 index for nonrecurrent tumours was 1.63% (0.08-9.36%), while for recurrent tumours it was 1.92% (0-7.76%). The percentage of p53 positive adenomas was 66% for nonrecurrent tumours and 68% for recurrent tumours. None of the differences in the labelling indices between the recurrent and nonrecurrent groups was statistically significant. As 12 patients (38%) in the nonrecurrent group had undergone radiotherapy as initial adjuvant therapy after surgery and none of the recurrent group had done so, patients who did not receive radiotherapy in the nonrecurrent group were analyzed separately. Again, none of the differences in the labelling indices between the recurrent and nonrecurrent groups was statistically significant when the effect of radiotherapy was removed from the analysis.

Conclusions:

The results demonstrate no statistical difference in the p53 or MIB-1 labelling indices between recurrent and nonrecurrent nonfunctional pituitary adenomas. Concern should be raised in attaching too much clinical significance to these labelling indices, especially with respect to p53 as a predictor of the clinical behavior of nonfunctional pituitary adenomas.

Résumé:

RÉSUMÉ:Introduction:

Dans les adénomes hypophysaires, il existe une corrélation entre un comportement envahissant de la tumeur et l’expression de la p53 et une augmentation de l’index de prolifération MIB-1. Le but de cette étude était de déterminer si ces indices pouvaient être utilisés pour prédire le risque de récidive des adénomes hypophysaires cliniquement non fonctionnels et ainsi guider le traitement adjuvant.

Méthodes:

Cinquante et un adénomes hypophysaires cliniquement non fonctionnels, dont 32 étaient non récurrents et 19 récurrents, ont été sélectionnés dans la base de données du Vancouver Hospital et du Health Sciences Center entre 1990 et 1998.

Résultats:

L’index de marquage initial moyen pour la p53 était de 0,38% pour les tumeurs non récurrentes (0-1,58%) et de 0,46% (0-3,65%) pour les adénomes récurrents. L’index MIB-1 initial moyen pour les tumeurs non récurrentes était de 1,63% (0,08-9,36%) et de 1,92% (0-7,76%) pour les tumeurs récurrentes. Soixante-six pour cent des adénomes non récurrents et 68% des adénomes récurrents étaient positifs pour la p53. Aucune des différences entre les indices de marquage entre les deux groupes n’atteignait le seuil de significativité. Étant donné que 12 patients (38%) du groupe ayant un adénome non récurrent avaient subi de la radiothérapie comme traitement adjuvant initial après la chirurgie et qu’aucun n’en avait reçu dans le groupe ayant un adénome récurrent, les données des patients qui n’ont par reçu de radiothérapie dans le groupe ayant un adénome non récurrent ont été analysées séparément. Aucune des différences entre les deux groupes dans les indices de marquage n’atteignait le seuil de significativité quand l’effet de la radiothérapie était retiré de l’analyse.

Conclusions:

Ces résultats ne démontrent aucune différence statistique dans les indices de marquage par l’anticorps de la p53 et de MIB-1 entre les adénomes hypophysaires non fonctionnels récurrents et non récurrents. On doit se garder d’attribuer une trop grande signification clinique à ces indices de marquage, surtout quant à la p53, pour prédire l’évolution clinique des adénomes hypophysaires non fonctionnels.

Type
Research Article
Information
Canadian Journal of Neurological Sciences , Volume 30 , Issue 3 , August 2003 , pp. 215 - 219
Copyright
Copyright © The Canadian Journal of Neurological 2003

References

1. Hollstein, M, Sidransky, D, Vogelstein, B, Harris, C. p53 mutations inhuman cancer. Science 1991;256:49–53.CrossRefGoogle Scholar
2. Pietilainen, T, Lipponen, P, Aaltomaa, S, et al. Expression of p53protein has no independent prognostic value in breast cancer. J Pathol 1995;177:225–232.CrossRefGoogle Scholar
3. Baas, I, Mulder, J, Offerhaus, G, et al. An evaluation of six antibodiesfor immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 1994;172:5–12.CrossRefGoogle Scholar
4. Xerri, L, Bouabdallah, R, Camerlo, J, Hassoun, J. Expression of thep53 gene in Hodgkin–s disease: dissociation between immunohistochemistry and clinicopathological data.Hum Pathol 1994;25:449–454.Google Scholar
5. Kennedy, S, MacGeogh, C, Jaffe, R, Spurr, N. Overexpression of theoncoprotein p53 in primary hepatic tumors of childhood does not correlate with gene mutations. Hum Pathol 1994;25:438–442.CrossRefGoogle Scholar
6. Cho, H, Ha, S, Park, S, et al. Role of p53 gene mutation in tumoraggressiveness of intracranial meningiomas. J Korean Med Sci 1999;14:199–205.CrossRefGoogle Scholar
7. Kyritsis, A, Bondy, M, Hess, K, et al. Prognostic significance of p53immunoreactivity in patients with glioma. Clin Cancer Res 1995;1:1617–1622.Google Scholar
8. Chozick, B, Pezzullo, J, Epstein, M, Finch, P. Prognostic implicationsof p53 overexpresion in supratentorial astrocytic tumors. Neurosurgery 1994;35:831–838.CrossRefGoogle Scholar
9. Montine, T, Bruner, J, Vandersteenhoven, J, et al. Prognosticsignificance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms. Diagn Mol Pathol 1994;3:240–245.Google Scholar
10. Buckley, N, Bates, A, Broome, J, et al. p53 protein accumulates inCushing’s adenomas and invasive nonfunctional adenomas. [corrected and republished article originally printed in J Clin Endocrinol Metab 1994;79(5):1513-1516] J Clin EndocrinolMetab 1995;80:4 pages following 692.Google Scholar
11. Buchfelder, M, Fahlbusch, R, Adams, E, et al. Proliferationparameters for pituitary adenomas. Acta Neurochir (Wien) 1996;65(Suppl):18–21.Google Scholar
12. Thapar, K, Scheithauer, B, Kovacs, K, et al. p53 expression inpituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 1996;38:765–771.CrossRefGoogle ScholarPubMed
13. Blevins, L, Verity, D, Allen, G. Aggressive pituitary tumours. Oncology 1998;12:1307–1315.Google Scholar
14. Pernicone, P, Scheithauer, B, Sebo, T, et al. Pituitary carcinoma. Cancer 1997;79:804–812.3.0.CO;2-3>CrossRefGoogle ScholarPubMed
15. Herman, V, Drazin, N, Gonsky, R, Melmed, S. Molecular screening ofpituitary adenomas for gene mutations and rearrangements. J ClinEndocrinol Metab 1993;77:50–55.Google Scholar
16. Perrett, C, Clayton, R, Pistorello, M, et al. GSTM1 and CYP2D6genotype frequencies in patients with pituitary tumours: effects on p53, ras and gsp. Carcinogenesis 1995;16:1643–1645.Google Scholar
17. Green, V, White, M, Hipkin, L, et al. Apoptosis and p53 suppressorgene protein expression in human anterior pituitary adenomas. Eur J Endocrinol 1997;136:382–387.Google Scholar
18. Levy, A, Hall, L, Yeudall, W, Lightman, S. p53 gene mutations inpituitary adenomas: rare events. Clin Endocrinol (Oxf) 1994;41:809–814.CrossRefGoogle ScholarPubMed
19. Gandour-Edwards, R, Kapadia, S, Janecka, I, et al. Biologic markersof invasive pituitary adenomas involving the sphenoid sinus. Mod Pathol 1995;8:160–164.Google Scholar
20. Litofsky, N, Recht, L. The impact of p53 tumor suppresor gene onglioma biology. Neurosurg Focus. 1997;3:Article 4.Google Scholar
21. Louis, D. The p53 gene and protein in human brain tumors. JNeuropathol Exp Neurol 1994;53:11–21.Google Scholar
22. Levine, A, Momand, J, Finlay, C. The p53 tumor suppressor gene. Nature 1991;351:453–456.Google Scholar
23. Harris, C, Hollstein, M. Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 1993;329:1318–1327.Google Scholar
24. Gerdes, J, Lemke, H, Baisch, H, et al. Cell cycle analysis of a cellproliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 1984;133:1710–1715.Google Scholar
25. Jaros, E, Perry, R, Adam, L, et al. Prognostic implications of p53protein, epidermal growth factor receptor, and Ki-67 labelling in brain tumours. Br J Cancer 1992;66:373–385.Google Scholar
26. Miyagami, M, Nakamura, S. Significance of p53 protein expressionand proliferative potential with MIB-1 on tumor recurrence of pituitary adenomas. No To Shinkei 1998;50:27–32.Google Scholar
27. Muller, W, Saeger, W, Wellhausen, L, et al. Markers of function andproliferation in noninvasive and invasive bi- and plurihormonal adenomas of patients with acromegaly: an immunohistochemicalstudy. Pathol Res Pract 1999;195:595–603.Google Scholar
28. Thapar, K, Kovacs, K, Scheithauer, B, et al. Proliferative activity andinvasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 1996;38:99–107.Google Scholar
29. Losa, M, Frankin, A, Mangili, F, et al. Proliferation index ofnonfunctioning pituitary adenomas: correlations with clinical characteristics and long-term follow-up results. Neurosurgery 2000;47:1313–1319.Google Scholar
30. Asa, S, Kovacs, K. Clinically nonfunctioning human pituitaryadenomas. Can J Neurol Sci 1992;19:228–235.Google Scholar
31. Samejima, N, Yamada, S, Takada, K, et al. Serum α-subunit levels inpatients with pituitary adenomas. Clin Endocrinol (Oxf) 2001;54:479–484.CrossRefGoogle Scholar
32. Ciric, I, Mikhael, M, Stafford, T, et al. Transsphenoidal microsurgeryof pituitary macroadenomas with long-term follow-up results. J Neurosurg 1983;59:395–401.CrossRefGoogle Scholar
33. Gee, J, Douglas-Jones, A, Hepburn, P, et al. A cautionary noteregarding the application of Ki-67 antibodies to paraffin-embedded breast cancers. J Pathol 1995;177:285–293.Google Scholar
34. Pegolo, G, Buckwalter, J, Weiss, M. Pituitary adenomas: correlationof the cytologic appearance with biologic behavior. Acta Cytol 1995;39:887–892.Google Scholar
35. Knosp, E, Kitz, K, Perneczky, A. Proliferation activity in pituitaryadenomas:measurement by monoclonal antibody Ki-67. Neurosurgery 1989;25:927–930.Google Scholar
36. Ebersold, M, Quast, L, ER Laws, J, et al. Long-term results intranssphenoidal removal of nonfunctioning pituitary adenomas. J Neurosurg 1986;64:713–719.Google Scholar
37. Scheithauer, B, Kovacs, K, ER Laws, J, Randall, R. Pathology ofinvasive pituitary tumors with special reference to functional classification. J Neurosurg 1986;65:733–744.CrossRefGoogle Scholar
38. Selman, W, ER Laws, J, Scheithauer, B, Carpenter, S. The occurenceof duralinvasioninpituitaryadenomas. J Neurosurg 1986;64:402–407.Google Scholar
39. Sautner, D, Saeger, W. Invasiveness of pituitary adenomas. PatholRes Pract 1991;187:632–636.CrossRefGoogle ScholarPubMed
40. Mindermann, T, Wilson, C. Thyrotropin-producing pituitaryadenomas. J Neurosurg 1993;79:521–527.Google Scholar
41. Fahlbusch, R, Honneger, J, Buchfelder, M. Surgical management ofacromegaly. Endocrinol Metab Clin North Am 1992;21:66–692.Google Scholar
42. Yonezawa, K, Tamaki, N, Kokunai, T. Clinical features and growthfractions of pituitary adenomas. Surg Neurol 1997;48:494–500.Google Scholar
43. Battifora, H. p53 immunohistochemistry: a word of caution.HumPathol 1994;25:435–436.Google Scholar
44. Clayton, R, Boggild, M, Bates, A, et al. Tumour suppressor genes inthe pathogenesis of human pituitary tumours. Horm Res 1997;47:185–193.Google Scholar