Differential gene expression by 1,25(OH)2D3 in an endometriosis stromal cell line.

Endometriosis is a common female reproductive disease characterized by invasion of endometrial cells into other organs, frequently causing pelvic pain and infertility. Alterations of the vitamin D system have been linked to endometriosis incidence and severity. To shed light on the potential mechanism for these associations, we examined the effects of 1,25(OH)2D3 on gene expression in endometriosis cells. Stromal cell lines derived from endometriosis tissue were treated with 1,25(OH)2D3, and RNA-seq was used to identify genes differentially expressed between treated and untreated cells. Gene ontology and pathway analyses were carried out using Partek Flow and Ingenuity software suites, respectively. We identified 1627 genes that were differentially expressed (886 down-regulated and 741 up-regulated) by 1,25(OH)2D3. Only one gene, CYP24A1, was strongly up-regulated (369-fold). Many genes were strongly down-regulated. 1,25(OH)2D3 treatment down-regulated several genetic pathways related to neuroangiogenesis, cellular motility, and invasion, including pathways for axonal guidance, Rho GDP signaling, and matrix metalloprotease inhibition. These findings support a role for vitamin D in the pathophysiology of endometriosis, and provide new targets for investigation into possible causes and treatments.

Breast pathology second review identifies clinically significant discrepancies in over 10% of patients.

BACKGROUND: Patients seeking a second opinion or continuation of care at our hospital will routinely have their pathology reviewed prior to initiating treatment. To assess the relevance of this review in patients with breast cancer, we compared original pathology reports submitted during the referral with second-review reports issued at our institution. We also assessed compliance with College of American Pathologists (CAP) requirements regarding inclusion of scientifically validated data elements (SVDE) in these pathology reports. METHODS: We retrospectively studied all 1,970 breast pathology referral cases reviewed during one calendar year. The variables studied were histologic classification; tumor grade, necrosis, size, margin status, lymphatic/vascular invasion, dermal involvement, and biomarker profile (ER, PR, and Her-2). Each variable was rated as "agree," "disagree," "missing information," or "not applicable." RESULTS: A significant discrepancy, defined as a disagreement that affected patient care, was found in 226 cases (11.47%). Additionally, in 418 resection cases (31.6%), some CAP-checklist specific required information was missing. The most common areas of significant discrepancy were histologic category (66 cases; 33%) and biomarker reporting (50 cases; 25%). The most problematic diagnostic categories were intraductal lesions, lobular carcinoma, metaplastic carcinomas, and phyllodes tumors. Most disagreements in the biomarker-profile category were interpretive, but in 20% of discrepant cases, findings were supported by repeat immunohistochemical analysis. CONCLUSIONS: Our results confirm the value and utility of obtaining a second opinion to optimize patient care. Changes in diagnoses obtained after second review should be interpreted and reported in a collaborative fashion, noting the benefit of a review from second pair of experienced eyes. Our results support the use of second review to ensure inclusion of CAP-required data elements in pathology reports.