TissuPath research update ~ April 2012

TissuPath research

TissuPath is committed to medical and scientific research, with a special focus on prostate cancer.  Our prostate cancer research is focused on using  information obtained from pathology review and additional analysis, in an attempt to identify “good” or “bad” prostate cancers, with the aim of improving the ability of surgeons and other clinicians in managing patients with prostate cancer. TissuPath staff are also currently involved in projects researching bladder cancer, kidney cancer and melanoma, along with projects involving broader clinical research, technical and scientific processes.

Here’s a brief synopsis of a few of our active projects;

A new Australian ‘active surveillance’ nomogram for prostate cancer

In our last update we informed you of the collaboration between TissuPath doctors, Dr Andrew Ryan and Professor John Mills’ and Western Australia pathologist Professor Ronnie Cohen to create a new ‘active surveillance in prostate cancer’ nomogram. Constructed using data from more than 2500 Australian men, the new nomogram provides more appropriate decision making information for Australian urologists and their patients. The nomogram and associated article have been recently published in The Journal of Urology.

  • O’Brien BA, Cohen RJ, Ryan A, Sengupta S, Mills J. A new preoperative nomogram to predict minimal prostate cancer: accuracy and error rates compared to other tools to select patients for active surveillance. J Urol. 2011 Nov;186(5):1811-7.

Assessing the significance of positive margins in prostate cancer.

A/Prof John Pedersen, working with scientists and urologic surgeons in Australia and Canada, has been investigating the significance of ‘positive margins’ in patients who have had a radical prostatectomy for cancer. A ‘positive margins’ is reported by a pathologist when cancer cells are identified, usually microscopically, at the inked surface of the specimen. Conventional thinking has been that this finding has a bad prognosis in all patients, however his recently published study indicates that it is only a bad prognostic factor in patients with ‘intermediate’ risk disease (intermediate risk: PSA 10-20 ng/dL, pT2 stage and/or Gleason score 7).  In patients with low or high-risk disease, the outcomes are directed by tumor biology, not whether positive margins are present. The paper reporting these results is in press in the British Journal of Urology International (BJU Int).

  • Corcoran NM, Hovens CM, Metcalfe C, Hong MK, Pedersen J, Casey RG, Peters J, Harewood L, Goldenberg SL, Costello AJ, Gleave ME. Positive surgical margins are a risk factor for significant biochemical recurrence only in intermediate-risk disease. BJU Int. 2012 Jan 18. doi: 10.1111/j.1464-410X.2011.10868.x. [Epub ahead of print]
Assessing accuracy of Gleason scoring in small prostate cancers.

A/Prof John Pedersen has collaborated with scientists and urologists at the Australian Prostate Cancer Research unit at Epworth Hospital and from Canada to assess the accuracy of Gleason scoring of small (low volume) prostate cancers. The Gleason score of a tumour is determined by adding the two commonest Gleason patterns of a cancer, and is recognised as an important prognostic factor (whether a prostate cancer is “good” or “bad”).  Their data shows clearly that Gleason grading of small/low volume cancers is often inaccurate due to sampling error.  The paper was published last month in the British Journal of Urology 2012; 109:660-4

  • Corcoran NM, Hovens CM, Hong MK, Pedersen J, Casey RG, Connolly S, Peters J, Harewood L, Gleave ME, Goldenberg SL, Costello AJ. Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours. BJU Int. 2012 Mar;109(5):660-4.
PSA and upgrading of Gleason score from TRUS to radical prostectomy.
  • Corcoran NM, Casey RG, Hong MK, Pedersen J, Connolly S, Peters J, Harewood L, Gleave ME, Costello AJ, Hovens CM, Goldenberg SL. The ability of prostate-specific antigen (PSA) density to predict an upgrade in Gleason score between initial prostate biopsy and prostatectomy diminishes with increasing tumour grade due to reduced PSA secretion per unit tumour volume. BJU Int. 2011 Nov 15. doi: 10.1111/j.1464-410X.2011.10681.x. [Epub ahead of print]
Prognostic markers in prostate cancer

Professor John Mills and Alice Oliver, in collaboration with many of our client urologists (Mark Frydenberg, Justin S. Peters, Anthony Costello, Laurence Harewood, Christopher Love and Nicholas Redgrave) have investigated two proteins, RhoC and ZAG, as prognostic markers in patients with prostate cancer.  Their study has shown that expression of both proteins, singly or in combination, predicts a better outcome after surgery.  The paper reporting these results will be published shortly in the journal Pathology.

Prof John Mills and A/Prof John Pedersen are collaborating with scientists at the Victorian Cancer Council to assess whether a group of prognostic markers can improve our ability to separate ‘good’ prostate cancers (those unlikely to cause illness or death in the foreseeable future) from ‘ bad’ cancers, those more likely to spread outside the prostate or to metastasise.  The prognostic markers are being assessed by immunohistochemistry and preliminary data suggests that using data incorporating a panel of these prognostic markers can provide vital information about the cancer – beyond that provided by conventional pathology studies (e.g. Gleason scores).  This data is currently being prepared for publication.

Dr Sam Norden and  A/Prof John Pedersen are working with clinicians at Australian Prostate Cancer Research unit at Epworth Hospital, Royal Melbourne Hospital and Biotech company Avipep to assess tumour specific antigen TAG-72 expression in prostate cancer. This report has been finalised and is currently being reviewed for publication.

Prostate cancer tissue banking techniques

With Dr Michael Kerger from the Australian Prostate Cancer Research unit at Epworth Hospital, the pathologists at TissuPath have worked to refine the method by which fresh cancer tissue is obtained from surgically removed prostate glands, with the aim of improving the accuracy and yield of malignant  tissue being ’tissue banked’ for current and future research.

  • Kerger M, Hong MK, Pedersen J, Nottle T, Ryan A, Mills J, Peters JS, Moon D, Crowe H, Costello AJ, Corcoran NM, Hovens CM. Microscopic assessment of fresh prostate tumour specimens yields significantly increased rates of correctly annotated samples for downstream analysis. Pathology. 2012 Apr;44(3):204-8
Mammalian Scribble polarity protein

Dr Andrew Ryan has been collaborating with a team from Peter MacCallum’s Cell Cycle and Cancer Genetics Laboratory on the mammalian Scribble polarity protein and the possible role it might play in prostate cancer.  The paper reporting these results was recently published in the prestigious Journal of Clinical Investigation

  • Pearson HB, Perez-Mancera PA, Dow LE, Ryan A, Tennstedt P, Bogani D, Elsum I, Greenfield A, Tuveson DA, Simon R, Humbert PO. SCRIB expression is deregulated in human prostate cancer, and its deficiency in mice promotes prostate neoplasia. J Clin Invest. 2011 Nov;121(11):4257-67.
An improvement in research technique
  • Toivanen R, Berman DM, Wang H, Pedersen J, Frydenberg M, Meeker AK, Ellem SJ, Risbridger GP, Taylor RA. Brief report: a bioassay to identify primary human prostate cancer repopulating cells. Stem Cells. 2011 Aug;29(8):1310-4.

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