Jerome Jean-Gilles

Copy number and gene expression differences between African American and Caucasian American prostate cancer

BackgroundThe goal of our study was to investigate the molecular underpinnings associated with the relatively aggressive clinical behavior of prostate cancer (PCa) in African American (AA) compared to Caucasian American (CA) patients using a genome-wide approach.MethodsAA and CA patients treated with radical prostatectomy (RP) were frequency matched for age at RP, Gleason grade, and tumor stage. Array-CGH (BAC SpectralChip2600) was used to identify genomic regions with significantly different DNA copy number between the groups. Gene expression profiling of the same set of tumors was also evaluated using Affymetrix HG-U133 Plus 2.0 arrays. Concordance between copy number alteration and gene expression was examined. A second aCGH analysis was performed in a larger validation cohort using an oligo-based platform (Agilent 244K).ResultsBAC-based array identified 27 chromosomal regions with significantly different copy number changes between the AA and CA tumors in the first cohort (Fishers exact test, P < 0.05). Copy number alterations in these 27 regions were also significantly associated with gene expression changes. aCGH performed in a larger, independent cohort of AA and CA tumors validated 4 of the 27 (15%) most significantly altered regions from the initial analysis (3q26, 5p15-p14, 14q32, and 16p11). Functional annotation of overlapping genes within the 4 validated regions of AA/CA DNA copy number changes revealed significant enrichment of genes related to immune response.ConclusionsOur data reveal molecular alterations at the level of gene expression and DNA copy number that are specific to African American and Caucasian prostate cancer and may be related to underlying differences in immune response.

Clinical and pathologic features and clinical impact of false negative thyroid fine‐needle aspirations

Although thyroid fine‐needle aspiration (TFNA) is an excellent test in evaluating thyroid nodules, there are occasionally false negatives (FN). The clinical impact and pathologic features of FN TFNA is understudied in the peer‐reviewed literature.

A Case Series of Transformation of Teratoma to Primitive Neuroectodermal Tumor: Evolving Management of a Rare Malignancy

Primitive neuroectodermal tumor (PNET) is a pathologic diagnosis that encompasses several different tumor types, including central nervous system tumors and Ewing’s sarcomas. Teratoma, a common element of germ cell tumor (GCT), has the ability to transform to malignant PNET in a small number of patients. Making a definitive diagnosis of PNET is difficult given its deviation from elements of GCT and its non-specific pathologic findings. Establishing the diagnosis is crucial as PNETs respond poorly to standard platinum-based chemotherapy used for treatment of GCT. Primary treatment for PNET is surgical, though this is often not feasible in many patients due to extensive disease at diagnosis. As an alternative, chemotherapy regimens traditionally used for Ewing’s sarcoma, such as vincristine, doxorubicin and cyclophosphamide alternating with ifosfamide and etoposide, have shown limited efficacy in the neoadjuvant, adjuvant, and palliative settings. Future research should delineate the genetic underpinnings of PNET and develop therapeutic options accordingly.

Cautery artifact understages urothelial cancer at initial transurethral resection of large bladder tumours

INTRODUCTION We sought to determine how frequently cautery (thermal) artifact precludes an accurate determination of stage at initial transurethral resection of bladder tumour (TURBT) of large bladder tumours. METHODS We queried our institutions billing data to identify patients who underwent TURBT for large bladder tumours >5cm (CPT 52240) by two urologists at an academic centre from January 2009 through April 2013. Only patients who underwent initial-staging TURBT for urothelial cancer were included. Pathological reports were reviewed for stage, number of separate pathological specimens per TURBT, and presence of cautery artifact. Operative reports were reviewed for whether additional cold cup biopsies were taken of other suspicious areas of the bladder, resident involvement, and type of electrocautery. RESULTS We identified 119 patients who underwent initial staging TURBT for large tumours. Cautery artifact interfered with accurate staging in 7/119 (6%) of cases. Of these, six patients underwent restaging TURBT, with 50% percent experiencing upstaging to T2 disease. Tumour size, tumour grade, whether additional cold cup biopsies were taken, number of separate pathological specimens sent, and resident involvement were not associated with cautery artifact (all p>0.05). Bipolar resection had a higher rate of cautery artifact 5/42 (12%), compared to monopolar resection 2/77 (2.6%) approaching significance (p=0.095). CONCLUSIONS Cautery artifact may delay accurate staging at initial TURBT for large tumours by understaging up to 6% of patients.

Papillary Cystadenoma of the Epididymis: A Case Report and Review of the Literature

P apillary cystadenoma of the epididymis (PCE) is a rare epithelial tumor that occurs sporadically or in association with Von Hippel–Lindau disease (VHLD).[1] It is the second most common benign neoplasm of the epididymis after the adenomatoid tumor.[2] PCE was first described in 1956, and since then has been recorded in approximately 70 reports that have been published as of 2014.[2,3] Bilateral PCE is pathognomonic of VHLD. In unilateral PCE, a review of 59 cases by Odrzywolski and Mukhopadhyay found that the association to VHL disease is about 29.3%, compared to the two-thirds of patients found to be positive for VHL disease with bilateral PCE.[2] Unilateral PCE is a rare but benign manifestation of VHLD, and once the lesion has been properly identified by imaging, the patients generally have a good prognosis after complete excision.[3] In this case, the patient presented with a unilateral PCE with an established diagnosis of VHLD and previous history of renal cell carcinoma (RCC). In this case report, we present the sonographic features of the PCE in the setting of a patient with VHLD.

Testicular Microlithiasis in the Setting of Primary Extragonadal Germ Cell Tumor: A Case Series.

The clinical significance of testicular microlithiasis (TM) in patients with primary extragonadal germ cell tumor (EGCT) is not well understood. When EGCT is suspected, sonographic and physical examination of the testicles should be performed to evaluate for testicular lesion or atrophy; negative testicular ultrasound with current technology virtually excludes the possibility of occult primary lesion. Although EGCTs are known to be associated with elevated level of serum tumor markers, the utility of tumor markers in the presence of TM is not well understood. Current guidelines for TM follow-up and management do not include any potential correlation between TM and primary EGCT, an association that should be addressed on future updates.

Validation of GEMCaP as a DNA Based Biomarker to Predict Prostate Cancer Recurrence after Radical Prostatectomy

Purpose We aimed to validate GEMCaP (Genomic Evaluators of Metastatic Cancer of the Prostate) as a novel copy number signature predictive of prostate cancer recurrence. Materials and Methods We randomly selected patients who underwent radical prostatectomy at Cleveland Clinic or University of Rochester from 2000 to 2005. DNA isolated from the cancer region was extracted and subjected to high resolution array comparative genomic hybridization. A high GEMCaP score was defined as 20% or greater of genomic loci showing copy number gain or loss in a given tumor. Cox regression was used to evaluate associations between the GEMCaP score and the risk of biochemical recurrence. Results We report results in 140 patients. Overall 38% of patients experienced recurrence with a median time to recurrence of 45 months. Based on the CAPRA‐S (Cancer of the Prostate Risk Assessment Post‐Surgical) score 39% of the patients were at low risk, 42% were at intermediate risk and 19% were at high risk. The GEMCaP score was high (20% or greater) in 31% of the cohort. A high GEMCaP score was associated with a higher risk of biochemical recurrence (HR 2.69, 95% CI 1.51–4.77) and it remained associated after adjusting for CAPRA‐S score and age (HR 1.94, 95% CI 1.06–3.56). The C‐index of GEMCaP alone was 0.64, which improved when combined with the CAPRA‐S score and patient age (C‐index = 0.75). Conclusions A high GEMCaP score was associated with biochemical recurrence in 2 external cohorts. This remained true after adjusting for clinical and pathological factors. The GEMCaP biomarker could be an efficient and effective clinical risk assessment tool to identify patients with prostate cancer for early adjuvant therapy.