Identification of GENEtic Markers of Aggressiveness and Malignancy by Array Comparative Genomic Hybrization Analysis (CGH) (PITUIGENE)

January 20, 2017 updated by: Hospices Civils de Lyon

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.

Study Overview

Status

Completed

Conditions

Study Type

Observational

Enrollment (Actual)

213

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Lyon, France, 69003
        • Hospices Civils de Lyon - Groupement Hospitalier Est

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

Description

Inclusion Criteria:

  • Only patient with complete clinical, radiological and hormonal data available during yearly follow-up will be included.
  • Preoperative MRI will be used to classify the tumour as invasive, and postoperative MRI will be collected to confirm recurrence or progression of the tumour.
  • Presence of tumour fragments fixed in Holland-Bouin's fluid or Neutral Buffered Formalin fixative available for aCGH analysis.

Exclusion Criteria:

  • Patient who underwent systematic post-operative radiotherapy.
  • Patient presenting Multiple Endocrine Neoplasia type 1 (MEN1) or aryl hydrocarbon receptor interacting protein (AIP) mutation since mechanism of tumorigenesis are different to sporadic pituitary tumours.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
"Control" Group
Patients cured with no evidence of disease up to 5 years will be the controls.
"Case" Group
Patients, in recurrence or progression before 5 years will be the cases

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
DNA alterations associated with the prognosis of pituitary tumours.
Time Frame: At least 5 years of follow-up
To identify and quantify the genomic DNA alterations associated with the prognosis of pituitary tumours.
At least 5 years of follow-up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hospices Civils de Lyon

Investigators

  • Principal Investigator: Gérald RAVEROT, PhD - MD, Hospices Civils de Lyon

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2013

Primary Completion (Actual)

January 1, 2017

Study Completion (Actual)

January 1, 2017

Study Registration Dates

First Submitted

July 17, 2013

First Submitted That Met QC Criteria

July 17, 2013

First Posted (Estimate)

July 19, 2013

Study Record Updates

Last Update Posted (Estimate)

January 23, 2017

Last Update Submitted That Met QC Criteria

January 20, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • D50834

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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