Tissue collection

All patients who are approached by their treating urologist and agree to donate specimens are asked to give written informed consent for the tissue banking protocol. A comprehensive patient information sheet covers all aspects relevant to the study, ie purpose of collection, how the tissues and data are collected, risks involved, confidentiality, patient rights, use of the tissue, and contact persons. The consent form gives permission for collection of blood and prostate tissue, and gathering of patient demographics, collection of clinically relevant information, and tracking of patient progression after treatment, for inclusion in the BioResource database. Consent is also obtained where appropriate for application of patient questionnaires.

A blood sample is usually collected on the day of consenting, or immediately before surgery. Following radical surgery, prostate tissue is sampled according to the procedure developed by the participating site in consultation with the urologists and pathologists concerned. This method provides the highest quality of surgical pathology for the patient, while allowing sufficient cancer and non malignant tissue to be banked for future research. Only after all diagnostic pathology requirements are met will the tissue be released for research purposes. Tissue samples are collected prior to tissue fixation of the prostate. Usually between two to six 5mm or two 8mm punch biopsy cores, or two scalpel-removed samples are taken depending on the pathology service and the size of the prostate. Tissue bank personnel ensure that the donated specimens are frozen in the shortest possible time after removal of the prostate from the patient, and this time (preferably within 30 minutes) is recorded for tissue bank quality control purposes. Long delays in sampling permit degradation of RNA and cellular membrane proteins due to the high level of enzyme activity within the prostate.

During 2005/2006, da Vinci robot-assisted radical prostatectomy was introduced into several centres in Australia, and the proportion of radical surgery procedures utilizing this advanced technology is expected to progressively increase over the next 5-10 years. Although robotic surgery is of benefit to the patient in terms of reduced blood loss and shorter stay in hospital, the procedure results in an increased delay between the severing of the prostate blood supply and removal of the organ from the patient. This period of warm ischaemia (lack of oxygen) at body temperature can lead to changes in cell morphology visible under the microscope, but there is apparently little adverse effect on mRNA quality at the molecular level. A study to compare the immunostaining profile of tumour biomarkers between prostate tissues derived from conventional and robot-assisted radical prostatectomy is being conducted by the BioResource. 

The tissue collection being progressively acquired by the BioResource nodes comprises prospectively collected fresh frozen prostate tissue, blood plasma and serum, and white blood (buffy coat) cells. Samples of ejaculate and post ejaculatory urines for biomarker studies and isolation of metastatic cells are being collected by researchers in Brisbane and would be available on a collaborative research basis, to be arranged via the Project Manager. Tissue Micro-Arrays are being progressively constructed from paraffin-embedded prostate cancer blocks extracted from existing pathology archives, where the tissue blocks may be associated with up to 5-7 year data on clinical follow up of patient disease outcome.

Phase I Resources Available 

Each node has a collection of frozen and paraffin-blocked tissues that predates the formation of the BioResource. These collections have Institutional ethics approval for use in collaborative research with the team of investigators at the node concerned. Researchers may contact the National Project Manager with an outline of an ethically approved project and their tissue requirements. The Project Manager will then attempt to facilitate collaboration by contacting each node to determine whether they have the necessary tissue and data resources available.

Phase II Resources - Tissue Micro-Array Availability

As indicated in the outline of phase II operations of the BioResource (see About Us section), some TMA sets are complete and ready for release. TMA sets currently available are:

·          A human early stage prostate cancer progression array with Gleason score 4-9, and matching non-malignant tissue cores (n = 150 patients)

·          A pilot array with matching malignant and non-malignant cores from 10 men with early stage prostate cancer for initial testing for prostatic expression and optimisation of probe staining

·          An array for development of hormone resistance in a transgenic mouse model of prostate cancer (TRAMP)

·          A murine pilot array for preliminary testing of prostatic expression and optimisation of probe staining

TMAs of human prostate cancer cell line cultures are at the planning stage. All TMAs produced by the BioResource use 1mm tissue cores, usually in triplicate, with cancer and control non-malignant tissues from approximately 25-30 patients per block. Access to these resources is granted under the conditions outlined in the Tissue Access Policy document (see below). Partial cost recovery fees are payable (see below).

Phase III Resources – Frozen Tissue Availability 

As indicated in the outline of phase III operations of the BioResource provided in the About Us section, the prospective collection of tissues was initiated at all four nodes between October-December 2005. Also as indicated in the About Us section, release of the stored tissues from any single patient will be staged, with half being released immediately, and half after accumulation of 5 year clinical follow up data.

A Priority Access Policy for a reserve collection is in place for tissue contributory groups and other members assisting BioResource operations, for information please consult the Project Manager.

At the end of October 2006 (12 month accrual point for some nodes), the BioResource prospective collection contained the following for early stage prostate cancer treated by radical surgery:

Number of patients: 413

Number of patients providing frozen prostate samples: 325

Number of patients providing derived blood products: 304

Cost Recovery and Priority Access Policy

A partial cost recovery program is in place for late 2006-end 2007, in the first instance. Fees will be reviewed annually and any changes announced via this web page.

The full fee structure is payable by researchers not associated with the BioResource tissue collection or management for both frozen prospectively-collected tissues and for paraffin-embedded micro-arrayed tissues, but a discount applies for members of the BioResource. For further information please contact the Project Manager.

Current fees until December 2007 are:

Prospectively collected tissues:

• Frozen prostate tissue (20 microns supplied as 5 or 10 micron sections): A$185 per patient sample

• Blood products (Guthrie blots, frozen serum (0.5ml), plasma (0.5ml), buffy coat cells (0.2ml): A$30 per patient sample

Tissue microarrays:

• Human pilot array: 5 sections provided off a single block for testing of prostatic expression and reagent optimization: A$100

• Human test arrays: 1 section off a single block in an array (containing 25-30 patients): A$100 [eg a set of sections, one off each block in a 5-block array (containing a total of 125-150 patients) would cost A$500].

Additional sections or sets of sections may be purchased as required, with approval of the Tissue Access Committee.

Mouse (TRAMP) pilot and test arrays, and prostate cancer cell line arrays, fees to be determined, please consult the Project Manager.

Freight for frozen tissues (on dry ice) and microarrays (on wet ice) will be at the current commercial rate from the Institute holding the materials. There may be several freight bills for frozen tissues depending on the institutes from which they are derived.

Ethics Proforma  

The Ethics Sub-Committee of the BioResource has reviewed a number of patient information sheets and consent forms approved by local Institutional Ethics Committees (IEC) and in use by the contributing nodes. A proforma for both patient information sheet and consent form can be provided by the  Project Manager as a guide for investigators wishing to access materials, and who may need to demonstrate to their IEC the consent under which research tissues have been procured by the BioResource.

Recommended Standardised Guidelines for Collection & Storage Procedures - For Prospective Collections

These guidelines will be available from the Project Manager in due course 

Tissue Access Policy 

The BioResource has developed a tissue access policy using the guidelines provided by the NMHRC for tissue banks funded via the Enabling Grant initiative. 

Researchers can access copies of the following documents either via the link provided below, or by email from the Project Manager  

      Tissue Access Policy

      Letter of Intent

      Application Form

      Material Transfer Agreement - currently unavailable by website