Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH)
Condition: Pituitary Tumors
MeSH terms: Pituitary Neoplasms; Pituitary Diseases; Aggression
Study type: Observational

Summary: 
      Recent studies estimate that the prevalence of pituitary adenomas is approximately 1/1500
      persons. Pituitary tumours are usually considered as benign. However, local invasion is
      reported in 35-40% of pituitary adenomas; resistance to medical treatment or recurrence
      leading to multimodal therapy is reported in about 15% of cases. These tumours are considered
      as aggressive pituitary tumours and present a distinct biological and clinical entity with
      continued growth despite multimodal therapy, including surgery and radiotherapy (McCormack et
      al., 2011). Whilst these tumours have malignant potential, the term of pituitary carcinoma is
      strictly reserved for those rare tumours (0.2%) with demonstrated craniospinal or systemic
      metastases (Heaney, 2011).

      Pituitary aggressive and malignant tumours are very difficult to control and ultimately prove
      to be lethal. It was suggested that early aggressive treatments (chemotherapy, radiotherapy)
      may control progression and occurrence of metastases. However, these therapeutic options are
      associated with important side effects limiting their use and the prediction of pituitary
      tumor behaviour remains a challenge. At the diagnosis, clinical signs are not specific and
      the results concerning proliferative factors (Ki-67 and P53), putative oncogenes (PTTG)
      conflict from one series to another.

      In a case-control retrospective study of a cohort of 410 patients (HYPOPRONOS), we validated
      a prognostic pathological classification based on histological and radiological data (J.
      Trouillas 2012 in preparation). Tumours were classified into 3 grades: grade 1= non-invasive
      tumour, grade 2= invasive tumour and grade 3 = aggressive-invasive tumor with the combination
      of radiological signs of invasion and 2 of 3 signs of increased proliferation (Ki-67
      index>3%, number of mitoses>2 per 10 fields at 400X, P53 nuclear detection).

      It is now widely accepted that cancer is a clonal disease, which arises from a single normal
      cell and progresses thanks to the accumulation of DNA alterations (Sanson et al., 2011). To
      identify the role of these DNA alterations, we conducted array CGH analysis limited to 13
      prolactin pituitary tumours, from frozen fragments, and identified allelic loss of chromosome
      11 associated with aggressiveness and malignancy (Wierinckx et al., 2011).

      To confirm these encouraging results we propose to conduct a study on a large series of
      tumours, fixed and embed, and to be correlated the results to clinical data.
    


Observational model: Case-Control
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        Patients presenting a pituitary tumour, including PRL, GH, ACTH and LH/FSH, operated on by
        transsphenoidal route between 1990 and 2008 with at least 5 years of follow-up
      
Biospecimen description: 
      Pituitary tumour DNA may be extracted from frozen or paraffin-embedded tumours.
    
Keywords: Pituitary; CGH array; Tumor