Artificial Intelligence-Based PTEN Loss Assessment as an Early Predictor of Prostate Cancer Metastasis After Surgery: A Multicenter Retrospective Study.

Phosphatase and tensin homolog (PTEN) loss is associated with adverse outcomes in prostate cancer and can be measured via immunohistochemistry. The purpose of the study was to establish the clinical application of an in-house developed artificial intelligence (AI) image analysis workflow for automated detection of PTEN loss on digital images for identifying patients at risk of early recurrence and metastasis. Postsurgical tissue microarray sections from the Canary Foundation (n = 1264) stained with anti-PTEN antibody were evaluated independently by pathologist conventional visual scoring (cPTEN) and an automated AI-based image analysis pipeline (AI-PTEN).

Analysis of MRE11 and Mortality Among Adults With Muscle-Invasive Bladder Cancer Managed With Trimodality Therapy.

Importance: Bladder-preserving trimodality therapy can be an effective alternative to radical cystectomy for treatment of muscle-invasive bladder cancer (MIBC), but biomarkers are needed to guide optimal patient selection. The DNA repair protein MRE11 is a candidate response biomarker that has not been validated in prospective cohorts using standardized measurement approaches.

Objective: To evaluate MRE11 expression as a prognostic biomarker in MIBC patients receiving trimodality therapy using automated quantitative image analysis.

Development and validation of a quantitative reactive stroma biomarker (qRS) for prostate cancer prognosis.

To develop and validate a new tissue-based biomarker that improves prediction of outcomes in localized prostate cancer by quantifying the host response to tumor. We use digital image analysis and machine learning to develop a biomarker of the prostate stroma called quantitative reactive stroma (qRS). qRS is a measure of percentage tumor area with a distinct, reactive stromal architecture.

Uncommon malignant renal tumors and atypical presentation of common ones: a guide for radiologists.

Objective: While the typical imaging features of the more common RCC subtypes have previously been described, they can at times have unusual, but distinguishing features. Rarer renal tumors span a broad range of imaging features, but they may also have characteristic presentations. We review the key imaging features of atypical presentations of malignant renal tumors and uncommon malignant renal tumors.

Correlation of High-Risk Soft Tissue Sarcoma Biomarker Expression Patterns with Outcome following Neoadjuvant Chemoradiation.

Background: Sarcoma mortality remains high despite adjuvant chemotherapy. Biomarker predictors of treatment response and outcome could improve treatment selection.

Methods: Tissue microarrays (TMAs) were created using pre- and posttreatment tumor from two prospective trials (MGH pilot and RTOG 9514) of neoadjuvant/adjuvant MAID chemotherapy and preoperative radiation.

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

Background: The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters.

Histologic Grading of Prostatic Adenocarcinoma Can Be Further Optimized: Analysis of the Relative Prognostic Strength of Individual Architectural Patterns in 1275 Patients From the Canary Retrospective Cohort.

Histologic grading remains the gold standard for prognosis in prostate cancer, and assessment of Gleason score plays a critical role in active surveillance management. We sought to optimize the prognostic stratification of grading and developed a method of recording and studying individual architectural patterns by light microscopic evaluation that is independent of standard Gleason grade. Some of the evaluated patterns are not assessed by current Gleason grading (eg, reactive stromal response).

Loss of Expression of AZGP1 Is Associated With Worse Clinical Outcomes in a Multi-Institutional Radical Prostatectomy Cohort.

Background: Given the uncertainties inherent in clinical measures of prostate cancer aggressiveness, clinically validated tissue biomarkers are needed. We tested whether Alpha-2-Glycoprotein 1, Zinc-Binding (AZGP1) protein levels, measured by immunohistochemistry, and RNA expression, by RNA in situ hybridization (RISH), predict recurrence after radical prostatectomy independent of clinical and pathological parameters.

Methods: AZGP1 IHC and RISH were performed on a large multi-institutional tissue microarray resource including 1,275 men with 5 year median follow-up.

A Molecular Model for Predicting Overall Survival in Patients with Metastatic Clear Cell Renal Carcinoma: Results from CALGB 90206 (Alliance).

Background: Prognosis associated with metastatic renal cell carcinoma (mRCC) can vary widely.

Methods: This study used pretreatment nephrectomy specimens from a randomized phase III trial. Expression levels of candidate genes were determined from archival tumors using the OpenArray® platform for TaqMan® RT-qPCR.

DGCR8 is essential for tumor progression following PTEN loss in the prostate.

In human prostate cancer, the microRNA biogenesis machinery increases with prostate cancer progression. Here, we show that deletion of the Dgcr8 gene, a critical component of this complex, inhibits tumor progression in a Pten-knockout mouse model of prostate cancer. Early stages of tumor development were unaffected, but progression to advanced prostatic intraepithelial neoplasia was severely inhibited.

Evaluation of ERG and SPINK1 by Immunohistochemical Staining and Clinicopathological Outcomes in a Multi-Institutional Radical Prostatectomy Cohort of 1067 Patients.

Distinguishing between patients with early stage, screen detected prostate cancer who must be treated from those that can be safely watched has become a major issue in prostate cancer care. Identification of molecular subtypes of prostate cancer has opened the opportunity for testing whether biomarkers that characterize these subtypes can be used as biomarkers of prognosis. Two established molecular subtypes are identified by high expression of the ERG oncoprotein, due to structural DNA alterations that encode for fusion transcripts in approximately ½ of prostate cancers, and over-expression of SPINK1, which is purportedly found only in ERG-negative tumors.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer.

Background: Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making.

Somatostatin imaging of neuroendocrine-differentiated prostate cancer.

After prolonged androgen deprivation therapy, a subset of castrate-resistant prostate cancer patients will develop neuroendocrine prostate cancer (NEPC) associated with resistance to further hormonal therapy and frequent visceral metastases. Imaging the presence of somatostatin receptors on the cancer cell surface may provide a readily available, noninvasive means to distinguish adenocarcinoma from NEPC. This distinction is important for therapeutic decision making and may open the door for developing novel radionuclide targets for the treatment of this aggressive subtype of prostate cancer.

Epigenomic characterization of locally advanced anal cancer: a radiation therapy oncology group 98-11 specimen study.

Background: The Radiation Therapy Oncology Group 98-11 clinical trial demonstrated the superiority of standard 5-fluorouracil/mitomycin-C over 5-fluorouracil/cisplatin in combination with radiation in the treatment of anal squamous cell cancer. Tumor size (>5 cm) and lymph node metastases are associated with disease progression. There may be key molecular differences (eg, DNA methylation changes) in tumors at high risk for progression.

Physical activity and prostate gene expression in men with low-risk prostate cancer.

Purpose: Vigorous physical activity after diagnosis of localized prostate cancer may reduce the risk of disease progression and prostate cancer-specific mortality. The molecular mechanisms by which physical activity may exert protective effects in the prostate remain unknown.

Methods: We examined the associations between self-reported physical activity and gene expression patterns in morphologically normal prostate tissue of 71 men with low-risk prostate cancer on active surveillance.

Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning.

Lung cancer in never smokers, which has been partially attributed to household solid fuel use (i.e., coal), is etiologically and clinically different from lung cancer attributed to tobacco smoking.

A model for the design and construction of a resource for the validation of prognostic prostate cancer biomarkers: the Canary Prostate Cancer Tissue Microarray.

Tissue microarrays (TMAs) provide unique resources for rapid evaluation and validation of tissue biomarkers. The Canary Foundation Retrospective Prostate Tissue Microarray Resource used a rigorous statistical design, quota sampling, a variation of the case-cohort study, to select patients for inclusion in a multicenter, retrospective prostate cancer TMA cohort. The study is designed to definitively validate tissue biomarkers of prostate cancer recurrence after radical prostatectomy.

Regional cell proliferation in microdissected human prostate specimens after heavy water labeling in vivo: correlation with prostate epithelial cells isolated from seminal fluid.

Purpose: Prostate cancer is detected with increasing frequency but has a highly variable natural history and prognosis and active surveillance of men with low-risk prostate cancer would benefit greatly from minimally invasive methods to identify progression. We describe here two novel in vivo metrics of cell proliferation in men with prostate neoplasia.

Experimental Design: Three groups of men drank heavy water, a nonradioactive, stable isotopic tracer for 14 to 28 days: (i) healthy men, (ii) men scheduled for transrectal core needle biopsy, and (iii) men scheduled for radical prostatectomy.

Isolation and genomic analysis of circulating tumor cells from castration resistant metastatic prostate cancer.

Background: The number of circulating tumor cells (CTCs) in metastatic prostate cancer patients provides prognostic and predictive information. However, it is the molecular characterization of CTCs that offers insight into the biology of these tumor cells in the context of personalized treatment.

Methods: We developed a novel approach to isolate CTCs away from hematopoietic cells with high purity, enabling genomic analysis of these cells.

Gene expression and biological pathways in tissue of men with prostate cancer in a randomized clinical trial of lycopene and fish oil supplementation.

Background: Studies suggest that micronutrients may modify the risk or delay progression of prostate cancer; however, the molecular mechanisms involved are poorly understood. We examined the effects of lycopene and fish oil on prostate gene expression in a double-blind placebo-controlled randomized clinical trial.

Methods: Eighty-four men with low risk prostate cancer were stratified based on self-reported dietary consumption of fish and tomatoes and then randomly assigned to a 3-month intervention of lycopene (n = 29) or fish oil (n = 27) supplementation or placebo (n = 28).