Application of Hereditary Renal Cell Carcinoma Risk Criteria to a Large Prospective Database.

AIMS: To evaluate the clinical impact of the Canadian criteria for identifying patients and families at risk for hereditary renal cell carcinoma (RCC). MATERIALS AND METHODS: The Canadian hereditary RCC risk criteria were applied to patients from 16 centres in the Canadian Kidney Cancer information system (CKCis) prospective database. The primary end point was the proportion of patients who met at least one criterion. RESULTS: Between January 2011 and May 2017, 8388 patients were entered in the database; 291 had inadequate risk data; 2827 (35%) met at least one criterion for genetic testing (at-risk population). Most (83%) met just one criterion. The criterion of non-clear cell histology contributed the largest proportion of at-risk patients (59%), followed by age ≤ 45 years (28%). Sixty-one patients had documentation of genetic testing, with 56 being classified at-risk (2% of at-risk). Twenty patients (35%) of the patients at risk and tested for hereditary RCC were found to harbour a germline mutation. CONCLUSIONS: Application of the Canadian hereditary RCC risk criteria to a large prospective database resulted in 35% of patients being identified at risk for hereditary RCC who could qualify for genetic testing. However, the true incidence of hereditary RCC in this population is unknown as most patients did not have documented genetic testing carried out and, thus, the sensitivity and specificity of the criteria cannot be determined. The low proportion of at-risk patients who underwent genetic testing is disappointing and highlights that there may be gaps in reporting, knowledge and/or barriers in access to genetic testing.

NF-kappa B nuclear localization and its prognostic significance in prostate cancer.

OBJECTIVE: To detect the subcellular localization of NF-kappa B (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappa B localization alone, or combined with the histological grade, can be used to predict patient outcome. PATIENTS AND METHODS: Prostate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappa B was visualized by immunohistochemistry using an anti-p65 antibody. RESULTS: The NF-kappa B subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappa B was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappa B was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappa B nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappa B subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappa B) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappa B; P = 0.004). CONCLUSION: NF-kappa B is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappa B as a prognostic factor.

Gleason score on biopsy: is it reliable for predicting the final grade on pathology?

OBJECTIVE: To assess the correlation of the Gleason score on biopsy and the final pathology after radical prostatectomy (RP) for prostate adenocarcinoma. PATIENTS AND METHODS: In a retrospective analysis within a tertiary-care centre, the charts of 537 patients who had undergone radical prostatectomy from April 1989 to November 2000 were reviewed. The RPs were undertaken in one institution; 167 biopsies were taken and interpreted in the referring centres, and 355 were taken and interpreted in the authors' institution by up to 15 pathologists. All the final pathology specimens were interpreted by the same group of pathologists. The main outcome measures were: the pathological report of the biopsy including the primary and secondary Gleason grade; the final pathological grade (primary and secondary); the margin status; and the identification of the pathologist for the biopsy and final pathology. RESULTS: In all, 390 patients had inclusion criteria (the Gleason grade before and after RP) available. For the individual scores 38.2% of tumours were undergraded, 32.6% overgraded and only 29.2% had identical grading in preoperative biopsies and final specimens. When grouped into more meaningful categories (Gleason 2-4, 5-6, 7 and 8-10) the correlation improved, with 48.5% of patients remaining in the same group after RP. For 39 patients the same pathologist assessed the biopsy and final specimen; in these cases individual scores were identical in 49% and group scores were identical in 64%. CONCLUSION: Gleason grading of the prostate biopsy remains a poor predictor of pathological outcome. Assessment by the same pathologist reduces the discrepancy but over half the patients are under- or overgraded on final pathology. Clinicians should be aware of these limitations when using the biopsy Gleason grade in decision making.