Evaluation of a genomic classifier in radical prostatectomy patients with lymph node metastasis.

OBJECTIVE: To evaluate the performance of the Decipher test in predicting lymph node invasion (LNI) on radical prostatectomy (RP) specimens. METHODS: We identified 1,987 consecutive patients with RP who received the Decipher test between February and August 2015 (contemporary cohort). In the contemporary cohort, only the Decipher score from RP specimens was available for analysis. In addition, we identified a consecutive cohort of patients treated with RP between 2006 and 2012 at the University of California, San Diego, with LNI upon pathologic examination (retrospective cohort). The retrospective cohort yielded seven, 22, and 18 tissue specimens from prostate biopsy, RP, and lymph nodes (LNs) for individual patients, respectively. Univariable and multivariable logistic regression analyses were used to evaluate the performance of Decipher in the contemporary cohort with LNI as the endpoint. In the retrospective cohort, concordance of risk groups was assessed using validated cut-points for low (0.60) Decipher scores. RESULTS: In the contemporary cohort, 51 (2.6%) patients had LNI. Decipher had an odds ratio of 1.73 (95% confidence interval, 1.46-2.05) and 1.42 (95% confidence interval, 1.19-1.7) per 10% increase in score on univariable and multivariable (adjusting for pathologic Gleason score, extraprostatic extension, and seminal vesicle invasion), respectively. No significant difference in the clinical and pathologic characteristics between the LN positive patients of contemporary and retrospective cohorts was observed (all P\u3e0.05). Accordingly, among LN-positive patients in the contemporary cohort and retrospective cohort, 80% and 77% had Decipher high risk scores (P=1). In the retrospective cohort, prostate biopsy cores with the highest Gleason grade and percentage of tumor involvement had 86% Decipher risk concordance with both RP and LN specimens. CONCLUSION: Decipher scores were highly concordant between pre- and post-surgical specimens. Further, Decipher scores from RP tissue were predictive of LNI at RP. If validated in a larger cohort of prostate biopsy specimens for prediction of adverse pathology at RP, Decipher may be useful for improved pre-operative staging

Evaluation of a genomic classifier in radical prostatectomy patients with lymph node metastasis

OBJECTIVE: To evaluate the performance of the Decipher test in predicting lymph node invasion (LNI) on radical prostatectomy (RP) specimens. METHODS: We identified 1,987 consecutive patients with RP who received the Decipher test between February and August 2015 (contemporary cohort). In the contemporary cohort, only the Decipher score from RP specimens was available for analysis. In addition, we identified a consecutive cohort of patients treated with RP between 2006 and 2012 at the University of California, San Diego, with LNI upon pathologic examination (retrospective cohort). The retrospective cohort yielded seven, 22, and 18 tissue specimens from prostate biopsy, RP, and lymph nodes (LNs) for individual patients, respectively. Univariable and multivariable logistic regression analyses were used to evaluate the performance of Decipher in the contemporary cohort with LNI as the endpoint. In the retrospective cohort, concordance of risk groups was assessed using validated cut-points for low (<0.45), intermediate (0.45–0.60), and high (>0.60) Decipher scores. RESULTS: In the contemporary cohort, 51 (2.6%) patients had LNI. Decipher had an odds ratio of 1.73 (95% confidence interval, 1.46–2.05) and 1.42 (95% confidence interval, 1.19–1.7) per 10% increase in score on univariable and multivariable (adjusting for pathologic Gleason score, extraprostatic extension, and seminal vesicle invasion), respectively. No significant difference in the clinical and pathologic characteristics between the LN positive patients of contemporary and retrospective cohorts was observed (all P>0.05). Accordingly, among LN-positive patients in the contemporary cohort and retrospective cohort, 80% and 77% had Decipher high risk scores (P=1). In the retrospective cohort, prostate biopsy cores with the highest Gleason grade and percentage of tumor involvement had 86% Decipher risk concordance with both RP and LN specimens. CONCLUSION: Decipher scores were highly concordant between pre- and post-surgical specimens. Further, Decipher scores from RP tissue were predictive of LNI at RP. If validated in a larger cohort of prostate biopsy specimens for prediction of adverse pathology at RP, Decipher may be useful for improved pre-operative staging

Tumor infiltrating B-cells are increased in prostate cancer tissue

BACKGROUND: The presence of increased B-cell tumor infiltrating lymphocytes (TILs) was seen in mouse prostate cancer (PCa) but has not been fully documented in human PCa. We, therefore, investigated the density of infiltrating B cells within human PCa utilizing a quantitative computational method. METHODS: Archived radical prostatectomy specimens from 53 patients with known clinical outcome and D’Amico risk category were obtained and immunohistochemically (IHC) stained for the B cell marker, CD20. Slides were reviewed by a genitourinary pathologist who manually delineated the tumoral regions of PCa. Slides were digitally scanned and a computer algorithm quantified the area of CD20 stained B-cells as a measure of B cell density within the outlined regions of prostate cancer (intra-tumoral region), versus extra-tumoral prostate tissue. Correlations were analyzed between B-cell density and demographic and clinical variables, including D’Amico risk groups and disease recurrence. RESULTS: For the entire cohort, the mean intra-tumoral B cell density was higher (3.22 SE = 0.29) than in the extra-tumoral region of each prostatectomy section (2.24, SE = 0.19) (paired t test; P < 0.001). When analyzed according to D’Amico risk group, the intra-tumoral B cell infiltration in low risk (0.0377 vs. 0.0246; p = 0.151) and intermediate risk (0.0260 vs. 0.0214; p = 0.579) patient prostatectomy specimens did not show significantly more B-cells within the PCa tumor. However, patient specimens from the high-risk group (0.0301 vs. 0.0197; p < 0.001) and from those who eventually had PCa recurrence or progression (0.0343 vs. 0.0246; p = 0.019) did show significantly more intra-tumoral CD20+ B-cell staining. Extent of B-cell infiltration in the prostatectomy specimens did not correlate with any other clinical parameters. CONCLUSIONS: Our study shows that higher B-cell infiltration was present within the intra-tumoral PCa regions compared to the extra-tumoral benign prostate tissue regions in prostatectomy sections. For this study we developed a new method to measure B-cells using computer-assisted digitized image analysis. Accurate, consistent quantitation of B-cells in prostatectomy specimens is essential for future clinical trials evaluating the effect of B cell ablating antibodies. The interaction of B-cells and PCa may serve as the basis for new therapeutic targets

Unclassified mucinous renal cell carcinoma: a rare histopathological entity.

Renal cell carcinoma (RCC) with mucin production is extremely rare. We present the case of a previously healthy 76-year-old woman who underwent a robotic-assisted laparoscopic right nephrectomy for a 5-cm heterogeneously enhancing right renal mass. Pathology revealed mucin-producing epithelial RCC. We discuss the presentation and pathological features of this case and comment on its definitive treatment

BRAF mutation as a novel driver of eosinophilic cystitis.

Eosinophilic cystitis is a rare manifestation of hypereosinophilia and a cause of morbidity, including dysuria and hematuria. Although some cases can be attributed to infection or allergy, most cases are assessed to be idiopathic and treated with corticosteroids. However, hypereosinophilia can also be due to actionable clonal molecular alterations in the haematopoietic cells, similar to other myeloproliferative neoplasms. Common mutations associated with eosonophilic syndromes are of platelet-derived growth factor receptor α or β or c-kit, though other pathogenic mutations have been found by next generation sequencing. Determination of a specific mutation may therefore identify clonality and refine treatment of some cases. Here we review the molecular features of eosinophilic disorders. We also describe the use of a liquid biopsy of circulating cell-free DNA in the workup of a case of eosinophilic cystitis in which next generation sequencing of cell-free DNA showed a BRAF I463T mutation. In silico modeling supports the functional impact and potential clinical relevance of BRAF I463T

BRAF mutation as a novel driver of eosinophilic cystitis.

Eosinophilic cystitis is a rare manifestation of hypereosinophilia and a cause of morbidity, including dysuria and hematuria. Although some cases can be attributed to infection or allergy, most cases are assessed to be idiopathic and treated with corticosteroids. However, hypereosinophilia can also be due to actionable clonal molecular alterations in the haematopoietic cells, similar to other myeloproliferative neoplasms. Common mutations associated with eosonophilic syndromes are of platelet-derived growth factor receptor α or β or c-kit, though other pathogenic mutations have been found by next generation sequencing. Determination of a specific mutation may therefore identify clonality and refine treatment of some cases. Here we review the molecular features of eosinophilic disorders. We also describe the use of a liquid biopsy of circulating cell-free DNA in the workup of a case of eosinophilic cystitis in which next generation sequencing of cell-free DNA showed a BRAF I463T mutation. In silico modeling supports the functional impact and potential clinical relevance of BRAF I463T