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    How to interpret Gleason score in contemporary biopsy

    Simple estimates can be used to account for the dramatic Gleason score shift over past decade


    Dr. Albertsen
    Urologists counseling men with newly diagnosed prostate cancer often assess the risk posed by the disease in order to recommend an appropriate treatment strategy. During the past decade, clinicians have recognized that men with elevated PSA levels have a significant chance of harboring extracapsular disease. Another indicator of potentially advanced disease is the number of biopsy cores that are positive for disease and the percentage of each core that contains disease.

    Pathologists have long known that tissue histology carries significant prognostic information. A.C. Broders, MD (Minn Med 1925; 8:726-30) was one of the first pathologists to classify neoplasia according to histology criteria. As pathologists became more familiar with prostate cancer, several classification schemes, many unique to the treating institution, were developed. The Johns Hopkins Hospital and the Mayo Clinic, for example, used systems developed by their own institution for grading prostate cancer.

    Gleason classification scheme

    Gerald L. Andriole, MD
    When the Veterans Administration Cooperative Urologic Oncology Group (VACURG) was organized, researchers faced a dilemma concerning how best to classify prostate cancer specimens of patients included in the study trials. They turned to Donald Gleason, MD, a pathologist at the Minneapolis VA Hospital, to act as a tissue referee.

    Figure1 : Distribution of Gleason scores: Original and contemporary readings
    Dr. Gleason had developed a classification scheme that relied on low-power observation of glandular architecture. He identified nine patterns of glandular growth that appeared to carry prognostic significance. Working with the Armed Forces Institute of Pathology, Dr. Gleason refined his scheme and developed the classic diagram now widely used of pathologists to grade prostate cancer specimens.

    Figure2 : Cause-specific survival curves based on Gleason scores from contemporary and original readings
    Prostate cancer diagnosis has changed dramatically since the 1960s. When Dr. Gleason participated in the VACURG studies, he frequently was handed large specimens to secure a diagnosis. Tissue usually came from transurethral resections, simple open prostatectomies, and either open or transperineal biopsies using large Vim-Silverman needles. After reviewing many glands throughout the specimen, Dr. Gleason was able to identify the dominant cancer pattern and the next most common cancer pattern. The grades assigned to these patterns were subsequently combined to arrive at a Gleason score.

    Current challenges

    Contemporary prostate biopsies offer a much greater challenge. Pathologists have minimal quantities of tissue to evaluate and frequently must make a diagnosis of prostate cancer based on a single cluster of glandular tissue. Not infrequently, the entire specimen consists of a single, small focus of prostate cancer, which the pathologist reluctantly calls either 3+3 disease or 4+4 disease. The two numbers do not reflect an assessment of different areas within the specimen, but are simply an artifact of the classification system.

    Urologists rarely see Gleason patterns 2 through 5 in contemporary urology practice. Have these cancers vanished, or have pathologists changed their reference standards?

    To address this problem, our group located pathology biopsy slides on 1,858 men living in Connecticut who were diagnosed with prostate cancer during the period 1990 to 1992. We asked an experienced pathologist who had worked extensively with Dr. Gleason to re-read these specimens in 2004 and 2005. We then compared the historical readings with the contemporary readings.