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Published in: Acta Neurochirurgica 12/2014

01-12-2014 | Clinical Article - Brain Tumors

An analysis of granulation patterns, MIB-1 proliferation indices and p53 expression in 101 patients with acromegaly

Authors: Sauradeep Sarkar, Ari George Chacko, Geeta Chacko

Published in: Acta Neurochirurgica | Issue 12/2014

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Abstract

Background

Despite the wide spectrum of adenoma behavior in patients with acromegaly, the ability of most pathological markers to predict clinical and radiological behavior remains controversial. The authors sought to comprehensively examine clinical and radiological correlates of growth hormone (GH)-secreting pituitary adenomas with regard to several commonly used immunocytochemical techniques in patients undergoing transsphenoidal surgery for acromegaly.

Method

We performed a retrospective review of histopathological findings in 101 surgically resected GH adenomas. Tumors were assessed radiologically for different patterns of extension. Each tumor specimen was subject to immunocytochemical analysis, including assessments of granulation patterns, MIB-1 labeling indices, prolactin cosecretion, p53 expression and mitotic activity. Endocrinological outcome was assessed in 93 patients, with remission defined by the 2010 consensus criteria.

Results

Most tumors were macroadenomas and almost half were invasive. When compared to densely granulated tumors, sparsely granulated adenomas were associated with a younger age at presentation, higher preoperative IGF-1 levels, elevated MIB-1 index and pure GH immunostaining, but did not differ significantly in terms of extrasellar invasion or outcome. Increased mitotic activity and p53 expression were also associated with higher proliferation indices and a younger age at presentation. Mixed GH/prolactin tumors demonstrated significantly higher remission rates, independent of variations in extrasellar growth. MIB-1 indices did not correlate with the preoperative GH/IGF-1 levels, adenoma size or Knosp grade.

Conclusion

The pathobiology of acromegaly is complex, and the clinicoradiological significance of subtyping on the basis of the markers employed in this study is debatable. Further investigation of newer molecular markers is warranted.
Literature
1.
go back to reference Albarel F, Castinetti F, Morange I, Conte‐Devolx B, Gaudart J, Dufour H, Brue T (2013) Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients. Clin Endocrinol (Oxf) 78:263–270CrossRef Albarel F, Castinetti F, Morange I, Conte‐Devolx B, Gaudart J, Dufour H, Brue T (2013) Outcome of multimodal therapy in operated acromegalic patients, a study in 115 patients. Clin Endocrinol (Oxf) 78:263–270CrossRef
2.
go back to reference Bakhtiar Y, Hirano H, Arita K, Yunoue S, Fujio S, Tominaga A, Sakoguchi T, Sugiyama K, Kurisu K, Yasufuku-Takano J (2010) Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae. Eur J Endocrinol 163:531–539PubMedCrossRef Bakhtiar Y, Hirano H, Arita K, Yunoue S, Fujio S, Tominaga A, Sakoguchi T, Sugiyama K, Kurisu K, Yasufuku-Takano J (2010) Relationship between cytokeratin staining patterns and clinico-pathological features in somatotropinomae. Eur J Endocrinol 163:531–539PubMedCrossRef
3.
go back to reference Bando H, Sano T, Ohshima T, Zhang C, Yamasaki R, Matsumoto K, Saito S (1992) Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma. Endocrinol Jpn 39:355–363PubMedCrossRef Bando H, Sano T, Ohshima T, Zhang C, Yamasaki R, Matsumoto K, Saito S (1992) Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma. Endocrinol Jpn 39:355–363PubMedCrossRef
4.
go back to reference Barkan AL, Stred SE, Reno K, Markovs M, Hopwood NJ, Kelch RP, Beitins IZ (1989) Increased growth hormone pulse frequency in acromegaly. J Clin Endocrinol Metab 69:1225–1233PubMedCrossRef Barkan AL, Stred SE, Reno K, Markovs M, Hopwood NJ, Kelch RP, Beitins IZ (1989) Increased growth hormone pulse frequency in acromegaly. J Clin Endocrinol Metab 69:1225–1233PubMedCrossRef
5.
go back to reference Bianchi A, Giustina A, Cimino V, Pola R, Angelini F, Pontecorvi A, De Marinis L (2009) Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab 94:2015–2022PubMedCrossRef Bianchi A, Giustina A, Cimino V, Pola R, Angelini F, Pontecorvi A, De Marinis L (2009) Influence of growth hormone receptor d3 and full-length isoforms on biochemical treatment outcomes in acromegaly. J Clin Endocrinol Metab 94:2015–2022PubMedCrossRef
6.
go back to reference Botelho CHA, Magalhães AV, Mello PA, Schmitt FC, Casulari LA (2006) Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin-secreting pituitary adenomas. Arq Neuropsiquiatr 64:60–66PubMedCrossRef Botelho CHA, Magalhães AV, Mello PA, Schmitt FC, Casulari LA (2006) Expression of p53, Ki-67 and c-erb B2 in growth hormone-and/or prolactin-secreting pituitary adenomas. Arq Neuropsiquiatr 64:60–66PubMedCrossRef
7.
go back to reference Chacko G, Chacko AG, Kovacs K, Scheithauer BW, Mani S, Muliyil J, Seshadri M (2010) The clinical significance of MIB-1 labeling index in pituitary adenomas. Pituitary 13:337–344PubMedCrossRef Chacko G, Chacko AG, Kovacs K, Scheithauer BW, Mani S, Muliyil J, Seshadri M (2010) The clinical significance of MIB-1 labeling index in pituitary adenomas. Pituitary 13:337–344PubMedCrossRef
8.
go back to reference Cottier JP, Destrieux C, Brunereau L, Bertrand P, Moreau L, Jan M, Herbreteau D (2000) Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology 215:463–469PubMedCrossRef Cottier JP, Destrieux C, Brunereau L, Bertrand P, Moreau L, Jan M, Herbreteau D (2000) Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology 215:463–469PubMedCrossRef
9.
go back to reference DeLellis R, Lloyd RV, Heitz P, Eng C (2004) World Health Organization classification of tumours: tumours of endocrine organs. IARC Press, Lyon DeLellis R, Lloyd RV, Heitz P, Eng C (2004) World Health Organization classification of tumours: tumours of endocrine organs. IARC Press, Lyon
10.
go back to reference Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797PubMed Esteller M, Hamilton SR, Burger PC, Baylin SB, Herman JG (1999) Inactivation of the DNA repair gene O6-methylguanine-DNA methyltransferase by promoter hypermethylation is a common event in primary human neoplasia. Cancer Res 59:793–797PubMed
11.
go back to reference Fougner SL, Casar‐Borota O, Heck A, Berg JP, Bollerslev J (2012) Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol (Oxf) 76:96–102CrossRef Fougner SL, Casar‐Borota O, Heck A, Berg JP, Bollerslev J (2012) Adenoma granulation pattern correlates with clinical variables and effect of somatostatin analogue treatment in a large series of patients with acromegaly. Clin Endocrinol (Oxf) 76:96–102CrossRef
12.
go back to reference Fusco A, Zatelli M, Bianchi A, Cimino V, Tilaro L, Veltri F, Angelini F, Lauriola L, Vellone V, Doglietto F (2008) Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab 93:2746–2750PubMedCrossRef Fusco A, Zatelli M, Bianchi A, Cimino V, Tilaro L, Veltri F, Angelini F, Lauriola L, Vellone V, Doglietto F (2008) Prognostic significance of the Ki-67 labeling index in growth hormone-secreting pituitary adenomas. J Clin Endocrinol Metab 93:2746–2750PubMedCrossRef
13.
go back to reference Hartman ML, Veldhuis JD, Vance ML, Faria AC, Furlanetto W, Thorner MO (1990) Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy. J Clin Endocrinol Metab 70:1375–1384PubMedCrossRef Hartman ML, Veldhuis JD, Vance ML, Faria AC, Furlanetto W, Thorner MO (1990) Somatotropin pulse frequency and basal concentrations are increased in acromegaly and are reduced by successful therapy. J Clin Endocrinol Metab 70:1375–1384PubMedCrossRef
14.
go back to reference Hazer DB, Işık S, Berker D, Güler S, Gürlek A, Yücel T, Berker M (2013) Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria: Clinical article. J Neurosurg 119:1467–1477PubMedCrossRef Hazer DB, Işık S, Berker D, Güler S, Gürlek A, Yücel T, Berker M (2013) Treatment of acromegaly by endoscopic transsphenoidal surgery: surgical experience in 214 cases and cure rates according to current consensus criteria: Clinical article. J Neurosurg 119:1467–1477PubMedCrossRef
15.
go back to reference Hentschel SJ, McCutcheon IE, Moore W, Durity FA (2003) P53 and MIB-1 immunohistochemistry as predictors of the clinical behavior of nonfunctioning pituitary adenomas. Can J Neurol Sci 30:215–219PubMed Hentschel SJ, McCutcheon IE, Moore W, Durity FA (2003) P53 and MIB-1 immunohistochemistry as predictors of the clinical behavior of nonfunctioning pituitary adenomas. Can J Neurol Sci 30:215–219PubMed
16.
go back to reference Hofstetter CP, Mannaa RH, Mubita L, Anand VK, Kennedy JW, Dehdashti AR, Schwartz TH (2010) Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus 29:E6PubMedCrossRef Hofstetter CP, Mannaa RH, Mubita L, Anand VK, Kennedy JW, Dehdashti AR, Schwartz TH (2010) Endoscopic endonasal transsphenoidal surgery for growth hormone-secreting pituitary adenomas. Neurosurg Focus 29:E6PubMedCrossRef
17.
go back to reference Jaffrain-Rea M, Di Stefano D, Minniti G, Esposito V, Bultrini A, Ferretti E, Santoro A, Scucchi LF, Gulino A, Cantore G (2002) A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer 9:103–113PubMedCrossRef Jaffrain-Rea M, Di Stefano D, Minniti G, Esposito V, Bultrini A, Ferretti E, Santoro A, Scucchi LF, Gulino A, Cantore G (2002) A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. Endocr Relat Cancer 9:103–113PubMedCrossRef
18.
go back to reference Kawamoto H, Uozumi T, Kawamoto K, Arita K, Yano T, Hirohata T (1995) Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas. Acta Neurochir (Wien) 136:37–43CrossRef Kawamoto H, Uozumi T, Kawamoto K, Arita K, Yano T, Hirohata T (1995) Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas. Acta Neurochir (Wien) 136:37–43CrossRef
19.
go back to reference Kiseljak-Vassiliades K, Shafi S, Kerr JM, Phang TL, Kleinschmidt-DeMasters B, Wierman ME (2012) Clinical implications of growth hormone–secreting tumor subtypes. Endocrine 42:18–28PubMedCrossRef Kiseljak-Vassiliades K, Shafi S, Kerr JM, Phang TL, Kleinschmidt-DeMasters B, Wierman ME (2012) Clinical implications of growth hormone–secreting tumor subtypes. Endocrine 42:18–28PubMedCrossRef
20.
go back to reference Kontogeorgos G, Sambaziotis D, Piaditis G, Karameris A (1997) Apoptosis in human pituitary adenomas: a morphologic and in situ end-labeling study. Mod Pathol 10:921–926PubMed Kontogeorgos G, Sambaziotis D, Piaditis G, Karameris A (1997) Apoptosis in human pituitary adenomas: a morphologic and in situ end-labeling study. Mod Pathol 10:921–926PubMed
21.
go back to reference Kovacs K, Scheithauer BW, Lombardero M, McLendon RE, Syro LV, Uribe H, Ortiz LD, Penagos LC (2008) MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy. Acta Neuropathol 115:261–262PubMedCrossRef Kovacs K, Scheithauer BW, Lombardero M, McLendon RE, Syro LV, Uribe H, Ortiz LD, Penagos LC (2008) MGMT immunoexpression predicts responsiveness of pituitary tumors to temozolomide therapy. Acta Neuropathol 115:261–262PubMedCrossRef
22.
go back to reference Kreutzer J, Vance M, Lopes M, Laws E (2001) Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 86:4072–4077PubMedCrossRef Kreutzer J, Vance M, Lopes M, Laws E (2001) Surgical management of GH-secreting pituitary adenomas: an outcome study using modern remission criteria. J Clin Endocrinol Metab 86:4072–4077PubMedCrossRef
23.
go back to reference Leontiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, Chahal HS, Igreja SC, Jordan S, Rowe J (2008) The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab 93:2390–2401PubMedCrossRef Leontiou CA, Gueorguiev M, van der Spuy J, Quinton R, Lolli F, Hassan S, Chahal HS, Igreja SC, Jordan S, Rowe J (2008) The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. J Clin Endocrinol Metab 93:2390–2401PubMedCrossRef
24.
go back to reference Lopes MBS (2010) Growth hormone-secreting adenomas: pathology and cell biology. Neurosurg Focus 29:E2PubMedCrossRef Lopes MBS (2010) Growth hormone-secreting adenomas: pathology and cell biology. Neurosurg Focus 29:E2PubMedCrossRef
25.
go back to reference Losa M, Barzaghi RL, Mortini P, Franzin A, Mangili F, Terreni MR, Giovanelli M (2000) Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors: comparison between micro-and macroadenomas. Am J Pathol 156:245–251PubMedCentralPubMedCrossRef Losa M, Barzaghi RL, Mortini P, Franzin A, Mangili F, Terreni MR, Giovanelli M (2000) Determination of the proliferation and apoptotic index in adrenocorticotropin-secreting pituitary tumors: comparison between micro-and macroadenomas. Am J Pathol 156:245–251PubMedCentralPubMedCrossRef
26.
go back to reference Mantovani G, Lania A, Spada A (2010) GNAS imprinting and pituitary tumors. Mol Cell Endocrinol 326:15–18PubMedCrossRef Mantovani G, Lania A, Spada A (2010) GNAS imprinting and pituitary tumors. Mol Cell Endocrinol 326:15–18PubMedCrossRef
27.
go back to reference Mastronardi L, Guiducci A, Spera C, Puzzilli F, Liberati F, Maira G (1999) Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody. J Clin Pathol 52:107–111PubMedCentralPubMedCrossRef Mastronardi L, Guiducci A, Spera C, Puzzilli F, Liberati F, Maira G (1999) Ki-67 labelling index and invasiveness among anterior pituitary adenomas: analysis of 103 cases using the MIB-1 monoclonal antibody. J Clin Pathol 52:107–111PubMedCentralPubMedCrossRef
28.
go back to reference Mayr B, Buslei R, Theodoropoulou M, Stalla GK, Buchfelder M, Schöfl C (2013) Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas. Eur J Endocrinol 169:391–400PubMedCrossRef Mayr B, Buslei R, Theodoropoulou M, Stalla GK, Buchfelder M, Schöfl C (2013) Molecular and functional properties of densely and sparsely granulated GH-producing pituitary adenomas. Eur J Endocrinol 169:391–400PubMedCrossRef
29.
go back to reference Mazal P, Czech T, Sedivy R, Aichholzer M, Wanschitz J, Klupp N, Budka H (2001) Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients. Clin Neuropathol 20:163–171PubMed Mazal P, Czech T, Sedivy R, Aichholzer M, Wanschitz J, Klupp N, Budka H (2001) Prognostic relevance of intracytoplasmic cytokeratin pattern, hormone expression profile, and cell proliferation in pituitary adenomas of akromegalic patients. Clin Neuropathol 20:163–171PubMed
30.
go back to reference McCormack AI, McDonald KL, Gill AJ, Clark SJ, Burt MG, Campbell KA, Braund WJ, Little NS, Cook RJ, Grossman AB (2009) Low O6‐methylguanine‐DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours. Clin Endocrinol (Oxf) 71:226–233CrossRef McCormack AI, McDonald KL, Gill AJ, Clark SJ, Burt MG, Campbell KA, Braund WJ, Little NS, Cook RJ, Grossman AB (2009) Low O6‐methylguanine‐DNA methyltransferase (MGMT) expression and response to temozolomide in aggressive pituitary tumours. Clin Endocrinol (Oxf) 71:226–233CrossRef
31.
go back to reference Mete O, Ezzat S, Asa SL (2012) Biomarkers of aggressive pituitary adenomas. J Mol Endocrinol 49:R69–R78PubMedCrossRef Mete O, Ezzat S, Asa SL (2012) Biomarkers of aggressive pituitary adenomas. J Mol Endocrinol 49:R69–R78PubMedCrossRef
32.
go back to reference Nehru GA, Pai R, Samuel P, Chacko AG, Chacko G (2012) Status of O 6-methylguanine-DNA methyltransferase [MGMT] gene promoter methylation among patients with glioblastomas from India. Neurol India 60:481–486PubMedCrossRef Nehru GA, Pai R, Samuel P, Chacko AG, Chacko G (2012) Status of O 6-methylguanine-DNA methyltransferase [MGMT] gene promoter methylation among patients with glioblastomas from India. Neurol India 60:481–486PubMedCrossRef
33.
go back to reference Nyquist P, Laws ER Jr, Elliott E (1994) Novel features of tumors that secrete both growth hormone and prolactin in acromegaly. Neurosurgery 35:179–184PubMedCrossRef Nyquist P, Laws ER Jr, Elliott E (1994) Novel features of tumors that secrete both growth hormone and prolactin in acromegaly. Neurosurgery 35:179–184PubMedCrossRef
34.
go back to reference Obari A, Sano T, Ohyama K, Kudo E, Qian ZR, Yoneda A, Rayhan N, Rahman MM, Yamada S (2008) Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol 19:82–91PubMedCrossRef Obari A, Sano T, Ohyama K, Kudo E, Qian ZR, Yoneda A, Rayhan N, Rahman MM, Yamada S (2008) Clinicopathological features of growth hormone-producing pituitary adenomas: difference among various types defined by cytokeratin distribution pattern including a transitional form. Endocr Pathol 19:82–91PubMedCrossRef
35.
go back to reference Osamura RY, Watanabe K (1987) Immunohistochemical colocalization of growth hormone (GH) and alpha subunit in human GH secreting pituitary adenomas. Virchows Arch A Pathol Anat Histopathol 411:323–30PubMedCrossRef Osamura RY, Watanabe K (1987) Immunohistochemical colocalization of growth hormone (GH) and alpha subunit in human GH secreting pituitary adenomas. Virchows Arch A Pathol Anat Histopathol 411:323–30PubMedCrossRef
36.
go back to reference Pan LX, Chen ZP, Liu YS, Zhao JH (2005) Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space. J Neurooncol 74:71–76PubMedCrossRef Pan LX, Chen ZP, Liu YS, Zhao JH (2005) Magnetic resonance imaging and biological markers in pituitary adenomas with invasion of the cavernous sinus space. J Neurooncol 74:71–76PubMedCrossRef
37.
go back to reference Sambaziotis D, Kapranos N, Kontogeorgos G (2003) Correlation of bcl-2 and bax with apoptosis in human pituitary adenomas. Pituitary 6:127–133PubMedCrossRef Sambaziotis D, Kapranos N, Kontogeorgos G (2003) Correlation of bcl-2 and bax with apoptosis in human pituitary adenomas. Pituitary 6:127–133PubMedCrossRef
38.
go back to reference Sano T, Ohshima T, Yamada S (1991) Expression of glycoprotein hormones and intracytoplasmic distribution of cytokeratin in growth hormone-producing pituitary adenomas. Pathol Res Pract 187:530–533PubMedCrossRef Sano T, Ohshima T, Yamada S (1991) Expression of glycoprotein hormones and intracytoplasmic distribution of cytokeratin in growth hormone-producing pituitary adenomas. Pathol Res Pract 187:530–533PubMedCrossRef
39.
go back to reference Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapcer Ö, Young WF Jr, Meyer FB, Kuroki T (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59:341–353PubMedCrossRef Scheithauer BW, Gaffey TA, Lloyd RV, Sebo TJ, Kovacs KT, Horvath E, Yapcer Ö, Young WF Jr, Meyer FB, Kuroki T (2006) Pathobiology of pituitary adenomas and carcinomas. Neurosurgery 59:341–353PubMedCrossRef
40.
go back to reference Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang Y-F, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA (2012) Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary 16:435–444CrossRef Shin SS, Tormenti MJ, Paluzzi A, Rothfus WE, Chang Y-F, Zainah H, Fernandez-Miranda JC, Snyderman CH, Challinor SM, Gardner PA (2012) Endoscopic endonasal approach for growth hormone secreting pituitary adenomas: outcomes in 53 patients using 2010 consensus criteria for remission. Pituitary 16:435–444CrossRef
41.
go back to reference Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M, Faglia G (1990) Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71:1421–1426PubMedCrossRef Spada A, Arosio M, Bochicchio D, Bazzoni N, Vallar L, Bassetti M, Faglia G (1990) Clinical, biochemical, and morphological correlates in patients bearing growth hormone-secreting pituitary tumors with or without constitutively active adenylyl cyclase. J Clin Endocrinol Metab 71:1421–1426PubMedCrossRef
42.
go back to reference Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA (2013) Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:3190–3198PubMedCrossRef Starke RM, Raper DM, Payne SC, Vance ML, Oldfield EH, Jane JA (2013) Endoscopic versus microsurgical transsphenoidal surgery for acromegaly: outcomes in a concurrent series of patients using modern criteria for remission. J Clin Endocrinol Metab 98:3190–3198PubMedCrossRef
43.
go back to reference Suliman M, Royds J, Cullen D, Timperley W, Powell T, Battersby R, Jones TH (2001) Mdm2 and the p53 pathway in human pituitary adenomas. Clin Endocrinol (Oxf) 54:317–325CrossRef Suliman M, Royds J, Cullen D, Timperley W, Powell T, Battersby R, Jones TH (2001) Mdm2 and the p53 pathway in human pituitary adenomas. Clin Endocrinol (Oxf) 54:317–325CrossRef
44.
go back to reference Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–107PubMedCrossRef Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER Jr (1996) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–107PubMedCrossRef
45.
go back to reference Yamada S, Aiba T, Sano T, Kovacs K, Shishiba Y, Sawano S, Takada K (1993) Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery 33:20–27PubMedCrossRef Yamada S, Aiba T, Sano T, Kovacs K, Shishiba Y, Sawano S, Takada K (1993) Growth hormone-producing pituitary adenomas: correlations between clinical characteristics and morphology. Neurosurgery 33:20–27PubMedCrossRef
46.
go back to reference Yonezawa MDK, Tamaki MDN, Kokunai MDT (1997) Clinical features and growth fractions of pituitary adenomas. Surg Neurol 48:494–500PubMedCrossRef Yonezawa MDK, Tamaki MDN, Kokunai MDT (1997) Clinical features and growth fractions of pituitary adenomas. Surg Neurol 48:494–500PubMedCrossRef
47.
go back to reference Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications: Clinical article. J Neurosurg 114:336–344PubMedCrossRef Zada G, Woodmansee WW, Ramkissoon S, Amadio J, Nose V, Laws ER Jr (2011) Atypical pituitary adenomas: incidence, clinical characteristics, and implications: Clinical article. J Neurosurg 114:336–344PubMedCrossRef
Metadata
Title
An analysis of granulation patterns, MIB-1 proliferation indices and p53 expression in 101 patients with acromegaly
Authors
Sauradeep Sarkar
Ari George Chacko
Geeta Chacko
Publication date
01-12-2014
Publisher
Springer Vienna
Published in
Acta Neurochirurgica / Issue 12/2014
Print ISSN: 0001-6268
Electronic ISSN: 0942-0940
DOI
https://doi.org/10.1007/s00701-014-2230-6

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