Prognostic factors in prolactin pituitary tumors: clinical, histological, and molecular data from a series of 94 patients with a long postoperative follow-up.

CONTEXT AND OBJECTIVE Predicting pituitary tumor behavior remains a challenge. This multiparameter investigation aimed to identify markers for recurrence and progression in prolactin tumors. DESIGN From a cohort of patients treated for prolactin tumors by surgery, we retrospectively studied clinical data, tumor characteristics, clinical outcome, and the expression of nine genes by quantitative RT-PCR. RESULTS This study included 94 patients (62 females and 32 men), with long postoperative follow-up periods (mean, 138 +/- 46 months); 54.3% of patients had a macro or giant adenoma. Tumors were classified into three pathological groups based on their radiological and histological characteristics (noninvasive, 61; invasive, 22; and aggressive-invasive, 11). Immediately after surgery, 60 patients (63.8%) went into remission (prolactin level normalization). Persistently elevated prolactin levels (36.2%) were associated with increasing age, male sex, high preoperative prolactin levels, large tumor size on univariate analysis, and invasion and pathological classification on univariate and multivariate (P = 8 x 10(-10) and 3 x 10(-8)) analysis. During follow-up, 19 patients (20%) had tumors that recurred or progressed under dopamine agonist treatment. Invasion and pathological classification were associated with recurrence or progression on univariate analysis. Seven genes (ADAMTS6, CRMP1, PTTG, ASK, CCNB1, AURKB, and CENPE) were associated with tumor recurrence or progression and five of these (ADAMTS6, CRMP1, ASK, CCNB1, and CENPE) were associated with the pathological classification. CONCLUSION This study identifies both the clinical and histological factors that relate to prolactin tumor recurrence or progression. Molecular markers give additional information for prognosis of such tumors. Altogether, our results could influence the management of patients with pituitary tumors.

[1]  Gordon B Mills,et al.  Integrative Analysis of Cyclin Protein Levels Identifies Cyclin B1 as a Classifier and Predictor of Outcomes in Breast Cancer , 2009, Clinical Cancer Research.

[2]  P. Cappabianca,et al.  HMGA proteins up-regulate CCNB2 gene in mouse and human pituitary adenomas. , 2009, Cancer research.

[3]  J. Hegemann,et al.  Transcriptional regulation of ASK/Dbf4 in cutaneous melanoma is dependent on E2F1 , 2008, Experimental dermatology.

[4]  J. Lachuer,et al.  A diagnostic marker set for invasion, proliferation, and aggressiveness of prolactin pituitary tumors. , 2007, Endocrine-related cancer.

[5]  N. Karavitaki,et al.  What are the markers of aggressiveness in prolactinomas? Changes in cell biology, extracellular matrix components, angiogenesis and genetics. , 2007, European journal of endocrinology.

[6]  C. Croce,et al.  HMGA2 induces pituitary tumorigenesis by enhancing E2F1 activity. , 2006, Cancer cell.

[7]  A. Colao,et al.  Advances in the treatment of prolactinomas. , 2006, Endocrine reviews.

[8]  Gavin D. Grant,et al.  Common markers of proliferation , 2006, Nature Reviews Cancer.

[9]  M. Buchfelder,et al.  Diagnosis and Management of Pituitary Carcinomas , 2005 .

[10]  B. Schaller.  Gender-related differences in prolactinomas. A clinicopathological study. , 2005, Neuro endocrinology letters.

[11]  G. Sassolas,et al.  Clinical and histological correlations in prolactinomas, with special reference to bromocriptine resistance , 2005, Acta Neurochirurgica.

[12]  A. Almasan,et al.  Opposing roles of E2Fs in cell proliferation and death , 2004, Cancer biology & therapy.

[13]  Viv Bewick,et al.  Statistics review 10: Further nonparametric methods , 2004, Critical care.

[14]  J. Shih,et al.  Connective tissue growth factor and its role in lung adenocarcinoma invasion and metastasis. , 2004, Journal of the National Cancer Institute.

[15]  A. Klibanski,et al.  Transsphenoidal surgery for pituitary tumors in the United States, 1996-2000: mortality, morbidity, and the effects of hospital and surgeon volume. , 2003, The Journal of clinical endocrinology and metabolism.

[16]  A. Tabarin,et al.  Polysialylated neural cell adhesion molecules expressed in human pituitary tumors and related to extrasellar invasion. , 2003, Journal of neurosurgery.

[17]  M. Losa,et al.  Surgical treatment of prolactin-secreting pituitary adenomas: early results and long-term outcome. , 2002, The Journal of clinical endocrinology and metabolism.

[18]  V. Esposito,et al.  A critical reappraisal of MIB-1 labelling index significance in a large series of pituitary tumours: secreting versus non-secreting adenomas. , 2002, Endocrine-related cancer.

[19]  E. Laws,et al.  The long-term significance of microscopic dural invasion in 354 patients with pituitary adenomas treated with transsphenoidal surgery. , 2002, Journal of neurosurgery.

[20]  G. Teasdale,et al.  Relapse of Hyperprolactinemia after Transsphenoidal Surgery for Microprolactinoma: Lessons from Long-term Follow-up , 2002, Neurosurgery.

[21]  Y. Benjamini,et al.  Controlling the false discovery rate in behavior genetics research , 2001, Behavioural Brain Research.

[22]  L. Brunereau,et al.  Cavernous sinus invasion by pituitary adenoma: MR imaging. , 2000, Radiology.

[23]  J. Honnorat,et al.  Ulip/CRMP proteins are recognized by autoantibodies in paraneoplastic neurological syndromes , 1999, The European journal of neuroscience.

[24]  S. Melmed,et al.  Early involvement of estrogen-induced pituitary tumor transforming gene and fibroblast growth factor expression in prolactinoma pathogenesis , 1999, Nature Medicine.

[25]  S. Melmed,et al.  Pituitary tumor transforming gene (PTTG) expression in pituitary adenomas. , 1999, The Journal of clinical endocrinology and metabolism.

[26]  K. Lamborn,et al.  Transsphenoidal microsurgical therapy of prolactinomas: initial outcomes and long-term results. , 1999, Neurosurgery.

[27]  J. Donckier,et al.  Sex-related difference in the growth of prolactinomas: a clinical and proliferation marker study. , 1997, The Journal of clinical endocrinology and metabolism.

[28]  S. Lightman,et al.  p53 gene mutations in pituitary adenomas: rare events , 1994, Clinical endocrinology.

[29]  E. Hedley‐Whyte,et al.  Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. , 1993, Journal of neurosurgery.

[30]  E. Knosp,et al.  Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. , 1989, Neurosurgery.

[31]  P. Cappabianca,et al.  HMGA Proteins Upregulate CCNB 2 Gene in Mouse and Human Pituitary Adenomas , 2009 .

[32]  C. Nimsky,et al.  Operative treatment of prolactinomas: indications and results in a current consecutive series of 212 patients. , 2008, European journal of endocrinology.

[33]  D. Figarella-Branger,et al.  The new WHO classification of human pituitary tumors: comments , 2005, Acta Neuropathologica.

[34]  A. Grossman.  The 2004 World health organization classification of pituitary tumors: is it clinically helpful? , 2005, Acta Neuropathologica.

[35]  M. Buchfelder,et al.  Clinical review: Diagnosis and management of pituitary carcinomas. , 2005, The Journal of clinical endocrinology and metabolism.

[36]  R. DeLellis.  Pathology and genetics of tumours of endocrine organs , 2004 .

[37]  E. Lander,et al.  A molecular signature of metastasis in primary solid tumors , 2003, Nature Genetics.

[38]  Cdm Fletcher,et al.  World Health Organization Classification of Tumours , 2002 .

[39]  B. Tang,et al.  ADAMTS: a novel family of extracellular matrix proteases. , 2001, The international journal of biochemistry & cell biology.

[40]  D. Figarella-Branger,et al.  Polysialylated-neural cell adhesion molecule expression in rat pituitary transplantable tumors (spontaneous mammotropic transplantable tumor in Wistar-Furth rats) is related to growth rate and malignancy. , 2000, Cancer research.