The genetic landscape of metaplastic breast cancers and uterine carcinosarcomas.

Metaplastic breast carcinoma (MBC) and uterine carcinosarcoma (UCS) are rare aggressive cancers, characterized by an admixture of adenocarcinoma and areas displaying mesenchymal/sarcomatoid differentiation. We sought to define whether MBCs and UCSs harbor similar patterns of genetic alterations, and whether the different histologic components of MBCs and UCSs are clonally related. Whole-exome sequencing (WES) data from MBCs (n = 35) and UCSs (n = 57, The Cancer Genome Atlas) were reanalyzed to define somatic genetic alterations, altered signaling pathways, mutational signatures, and genomic features of homologous recombination DNA repair deficiency (HRD). In addition, the carcinomatous and sarcomatous components of an additional cohort of MBCs (n = 11) and UCSs (n = 6) were microdissected separately and subjected to WES, and their clonal relatedness was assessed. MBCs and UCSs harbored recurrent genetic alterations affecting TP53, PIK3CA, and PTEN, similar patterns of gene copy number alterations, and an enrichment in alterations affecting the epithelial-to-mesenchymal transition (EMT)-related Wnt and Notch signaling pathways. Differences were observed, however, including a significantly higher prevalence of FAT3 and FAT1 somatic mutations in MBCs compared to UCSs, and conversely, UCSs significantly more frequently harbored somatic mutations affecting FBXW7 and PPP2R1A as well as HER2 amplification than MBCs. Genomic features of HRD and biallelic alterations affecting bona fide HRD-related genes were found to be more prevalent in MBCs than in UCSs. The distinct histologic components of MBCs and UCSs were clonally related in all cases, with the sarcoma component likely stemming from a minor subclone of the carcinoma component in the samples with interpretable chronology of clonal evolution. Despite the similar histologic features and pathways affected by genetic alterations, UCSs differ from MBCs on the basis of FBXW7 and PPP2R1A mutations, HER2 amplification, and lack of HRD, supporting the notion that these entities are more than mere phenocopies of the same tumor type in different anatomical sites

Comparing Single-Site and Multiport Robotic Hysterectomy with Sentinel Lymph Node Mapping for Endometrial Cancer: Surgical Outcomes and Cost Analysis

To compare operative times, surgical outcomes, and costs of robotic laparoendoscopic single-site (R-LESS) vs multiport robotic (MPR) total laparoscopic hysterectomy (TLH) with sentinel lymph node (SLN) mapping for low-risk endometrial cancer. Retrospective cohort study (Canadian Task Force classification II-2). Academic university hospital. Patients with a biopsy-proven diagnosis of complex atypical hyperplasia (CAH) or low-grade (1 or 2) endometrial cancer with body mass index <30 kg/m2 and undergoing robotic TLH and SLN mapping between 2012 and 2016 were included. Surgical outcomes and cost data were collected retrospectively and analyzed based on the surgical approach with R-LESS vs MPR assistance. Twenty-seven patients who met the inclusion criteria were identified, including 14 patients who underwent R-LESS TLH with SLN mapping and 13 patients who underwent MPR TLH with SLN mapping. Median uterine weight was comparable in the 2 cohorts (111.3 g vs 83.8 g; p = .33). Operative and console times were equivalent with the R-LESS and MPR approaches (median, 175 minutes vs 184 minutes, p = .61 and 136 vs 140 minutes, p = .12, respectively). Median estimated blood loss was 50 mL in both cohorts. Successful bilateral SLN mapping occurred in 85.7% of the R-LESS procedures and 76.9% of MPR procedures. No intraoperative or 30-day complications were encountered, and all patients were discharged within 23 hours of surgery. MPR was associated with additional disposable instrument and drape costs of $460 to$660 compared with R-LESS, depending on the surgeon's instrument selection. Average total hospital charges were lower for R-LESS procedures ($13,410 vs$15,952; p < .05). In highly selected patients with CAH or low-grade endometrial cancer undergoing TLH and SLN mapping, R-LESS appears to result in equivalent perioperative outcomes as a MPR approach while offering a more cost-effective option. Further research is needed to determine the benefits of R-LESS procedures in the gynecologic oncology setting

Flow diversion versus traditional aneurysm embolization strategies: analysis of fluoroscopy and procedure times

Background and objective Flow diverters are increasingly used for treatment of complex intracranial aneurysms. The purpose of this study was to compare the pipeline embolization device (PED) and traditional embolization strategies in terms of fluoroscopy and procedure time. Material and methods Fluoroscopy and procedure times (in minutes) were retrospectively analyzed and compared between 127 patients treated with the PED, 86 patients treated with single stage stent assisted coiling (SAC), and 16 patients treated with Onyx HD 500 at our institution. A multivariate logistic regression analysis was performed to determine independent predictors of fluoroscopy and procedure time. Results The three groups were comparable with respect to patient age, gender, and ruptured/unruptured aneurysm status. Aneurysms treated with the PED were significantly larger than stent coiled aneurysms, and aneurysm location distribution differed significantly between the three groups. Mean fluoroscopy time was significantly increased in the SAC (55±31 min, p<0.001) and Onyx HD 500 (91±36 min, p<0.001) groups relative to the PED group (34±23 min). Likewise, mean procedure time was significantly longer in SAC (155±50 min, p<0.001) and Onyx HD 500 (176±65 min, p<0.001) patients compared with PED patients (131±36 min). In multivariate analysis, SAC/Onyx HD 500 versus PED independently predicted longer procedure and fluoroscopy times. Conclusions PED treatment requires significantly shorter fluoroscopy and procedure times compared with SAC and Onyx HD 500. The results of this study may be used by advocates of flow diverters as an additional argument for using this treatment modality to treat intracranial aneurysms

Molecular subclasses of clear cell ovarian carcinoma and their impact on disease behavior and outcomes

PURPOSE: To identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes. EXPERIMENTAL DESIGN: We profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival. RESULTS: We detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy. CONCLUSIONS: Our study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness. See related commentary by Lheureux, p. 483

Molecular subclasses of clear cell ovarian carcinoma and their impact on disease behavior and outcomes

PurposeTo identify molecular subclasses of clear cell ovarian carcinoma (CCOC) and assess their impact on clinical presentation and outcomes.Experimental designWe profiled 421 primary CCOCs that passed quality control using a targeted deep sequencing panel of 163 putative CCOC driver genes and whole transcriptome sequencing of 211 of these tumors. Molecularly defined subgroups were identified and tested for association with clinical characteristics and overall survival.ResultsWe detected a putative somatic driver mutation in at least one candidate gene in 95% (401/421) of CCOC tumors including ARID1A (in 49% of tumors), PIK3CA (49%), TERT (20%), and TP53 (16%). Clustering of cancer driver mutations and RNA expression converged upon two distinct subclasses of CCOC. The first was dominated by ARID1A-mutated tumors with enriched expression of canonical CCOC genes and markers of platinum resistance; the second was largely comprised of tumors with TP53 mutations and enriched for the expression of genes involved in extracellular matrix organization and mesenchymal differentiation. Compared with the ARID1A-mutated group, women with TP53-mutated tumors were more likely to have advanced-stage disease, no antecedent history of endometriosis, and poorer survival, driven by their advanced stage at presentation. In women with ARID1A-mutated tumors, there was a trend toward a lower rate of response to first-line platinum-based therapy.ConclusionsOur study suggests that CCOC consists of two distinct molecular subclasses with distinct clinical presentation and outcomes, with potential relevance to both traditional and experimental therapy responsiveness. See related commentary by Lheureux, p. 4838