Low molecular weight serum cell-free DNA concentration is associated with clinicopathologic indices of poor prognosis in women with uterine cancer.

BACKGROUND: Serum cell-free DNA (cfDNA) holds promise as a non-invasive cancer biomarker. The objective of this study was to evaluate the association of cfDNA concentration with clinicopathologic variables of poor prognosis and overall survival among women with uterine cancer compared to benign cancer-free controls. METHODS: cfDNA was extracted from the serum of 91 women with multiple uterine cancer histologies and 22 post-menopausal controls without cancer. Low molecular weight (LMW) cfDNA was separated from contaminating genomic high molecular weight cfDNA using paramagnetic bead purification and its concentration was measured using fluorometric quantification. Clinicopathologic data was abstracted from the electronic medical record. The association between serum cfDNA concentration, clinicopathologic variables, and overall survival was assessed using linear regression modelling, Cox proportional hazards modelling, and the Kaplan-Meier method. RESULTS: Median total serum cfDNA concentration for the cohort was 69.2 ng/mL (IQR 37.4, 132.3) and median LMW cfDNA concentration was 23.8 ng/mL (IQR 14.9, 44.4). There were no significant differences in total serum cfDNA concentration with any clinicopathologic variables. However, LMW cfDNA concentration was significantly higher in serum of women with cancer (25.8 ng/mL IQR 16.0, 49.6) compared to benign controls (15.5 ng/mL IQR 9.3, 25.8 ng/mL) (p < 0.01). It is also significantly higher among women with early stage cancer than benign controls (p < 0.01). There were also significant associations between LMW cfDNA concentration and stage of cancer (p = 0.01) and histology (p = 0.02). Patients with leiomyosarcoma and carcinosarcoma had higher cfDNA concentrations than those with endometrioid cancer. Over a median follow-up of 51.9 months, 75th percentile for overall survival for women with cancer was 24.0 months. Higher LMW cfDNA concentrations is associated with lower survival among women with cancer (p < 0.01). CONCLUSIONS: Serum LMW cfDNA concentration is associated with overall survival in women with uterine cancer, and it is higher among women with uterine cancer compared to those of controls.

Comparative Use of Napsin A and Glypican 3 to Distinguish Endometrial Clear Cell from Serous and Endometrioid Carcinomas.

OBJECTIVE: Diagnosis of endometrial clear cell carcinomas is difficult owing to the low reproducibility of histological cell type in high-grade endometrial cancers. Recently, immunoreactivity for napsin A and glypican 3 has been reported in clear cell cancers. We sought to evaluate the use of napsin A and glypican 3 staining to distinguish clear cell carcinoma from other high-grade endometrial cancers. METHODS/MATERIALS: Twenty cases of pure and mixed endometrial clear cell carcinoma were extracted from the 2000-2014 archival material in the Departments of Obstetrics & Gynecology and Pathology at Montefiore Medical Center and compared to serous and grade 3 endometrioid controls. Representative sections were stained with monoclonal antibodies to napsin A and glypican 3. Immunostains were independently reviewed by 2 pathologists to assess frequency and pattern of staining. Charts were reviewed for clinicopathologic and treatment data. RESULTS: Granular cytoplasmic positivity for napsin A was observed in 70% of endometrial clear cell carcinomas; only 25% showed cytoplasmic or membranous glypican 3 positivity. No serous or high-grade endometrioid tumors stained for either marker. No cases of clear cell carcinoma that stained negative for napsin A stained positive for glypican 3. No difference in the immunohistochemical profile was found between pure and mixed clear cell carcinomas and between early- and advanced-stage clear cell carcinomas. CONCLUSIONS: Napsin A is a more sensitive marker for endometrial clear cell carcinoma than glypican 3. In histologically ambiguous cases, napsin A and glypican 3 may help distinguish clear cell carcinoma from other high-grade histologies. Further investigation of endometrial clear cell carcinoma is needed to identify additional diagnostic tools for this rare histology. Correlation of a unique immunohistochemical profile and clinical outcomes is necessary.

Educational Case: Ductal Carcinoma In Situ (DCIS).

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Triple-negative breast carcinoma: current and emerging concepts.

OBJECTIVES: Triple-negative breast cancer is regarded as an aggressive disease that affects a young patient population and for which effective targeted therapy is not yet available. METHODS: Intense efforts have been made to gain a better understanding of this heterogeneous group of tumors from the histologic to the genomic and molecular levels. RESULTS: Progress has been made, including the ability to subtype these tumors and the discovery of biomarkers toward which current therapeutic efforts are focused. Many novel targets under exploration have the potential to affect the clinical course of this disease. CONCLUSIONS: This article reviews the current concepts regarding the clinicopathologic features of triple-negative breast carcinoma, its histologic subtypes, molecular classification, the prognostic and therapeutic potential of biomarkers, and emerging targeted therapies.

Pediatric solid malignant neoplasms: a comparative analysis.

BACKGROUND: Pediatric solid malignant neoplasms (PSMNs) are a significant cause of death among children. Our aim was to evaluate the pattern and frequency of PSMNs at our hospital in the United States and compare the results to data from other regions of the world. MATERIALS AND METHODS: This is a retrospective review of 127 PSMNs in the Pathology database at Stony Brook University Medical Center (SBUMC) from 2000 to 2008. We compared our cases to a cohort of 101 cases from an academic hospital in India (1975-1982) (Christian Medical College and Hospital) and to reports from other parts of the world. RESULTS: We report a male to female ratio of 1.16 : 1 and a mean age of 4.8 years for cases at SBUMC. Lymphomas and central nervous system (CNS) neoplasms were more common in the 5-12-year-old group while other major diagnostic groups were more common in the 0-4-year-old group. The top five most frequent tumor categories included CNS, sympathetic nervous system (SNS), soft tissue, lymphoid and renal tumors. Lymphomas were more common than soft tissue and SNS tumors in the United States' registries but all three occurred with equal frequency in our study. Tumors of the soft tissue and SNS were more frequent at SBUMC compared to registries around the world. At the academic hospital in India, the male to female ratio was 4 : 1 and the five most frequent tumor categories included lymphoid, SNS, CNS, renal and bone tumors. Lymphoid tumors made up a greater percentage and CNS tumors made up a lesser percentage of tumors at the hospital in India compared with SBUMC. The differences between CNS tumors, lymphomas and retinoblastomas between the two hospitals were statistically significant (P value <0.05 by Fisher's Exact test). CONCLUSIONS: Geographic differences in the incidence and histologic types of PSMNs exist. Despite advancements in diagnosis and treatment, PSMNs continue to be tragically lethal.