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Robert soslow

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https://www.readbyqxmd.com/read/28417598/genetic-analysis-of-a-morphologically-heterogeneous-ovarian-endometrioid-carcinoma
#1
Felipe C Geyer, Fresia Pareja, Kathleen A Burke, Anne M Schultheis, Yaser R Hussein, Jiqing Ye, Maria R De Filippo, Caterina Marchio, Gabriel S Macedo, Salvatore Piscuoglio, Raymond S Lim, Eugene Toy, Rajmohan Murali, Achim A Jungbluth, Jorge S Reis-Filho, Robert A Soslow, Britta Weigelt
AIMS: Low-grade ovarian endometrioid carcinomas may be associated with high-grade components. Whether the latter are clonally-related to and originate from the low-grade endometrioid carcinoma remains unclear. Here we employed massively parallel sequencing to characterize the genomic landscape and clonal relatedness of an ovarian endometrioid carcinoma containing low- and high-grade components. METHODS AND RESULTS: DNA samples extracted from each tumor component (low-grade endometrioid, high-grade anaplastic, high-grade squamous) and matched normal tissue were subjected to targeted massively parallel sequencing using the 410 gene Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay...
April 18, 2017: Histopathology
https://www.readbyqxmd.com/read/28375931/a-comparison-of-the-detection-of-sentinel-lymph-nodes-using-indocyanine-green-and-near-infrared-fluorescence-imaging-versus-blue-dye-during-robotic-surgery-in-uterine-cancer
#2
Ane Gerda Eriksson, Anna Beavis, Robert A Soslow, Qin Zhou, Nadeem R Abu-Rustum, Ginger J Gardner, Oliver Zivanovic, Kara Long Roche, Yukio Sonoda, Mario M Leitao, Elizabeth L Jewell
OBJECTIVES: The objective of this study was to assess and compare the sentinel lymph node (SLN) detection rate with indocyanine green (ICG) and near-infrared fluorescence imaging versus blue dye using the robotic platform in patients with uterine cancer. METHODS: We identified all patients with uterine cancer undergoing SLN mapping using ICG or blue dye on the robotic platform from January 2011 to December 2013. Our institutional SLN algorithm and pathologic processing protocol were adhered to uniformly...
May 2017: International Journal of Gynecological Cancer
https://www.readbyqxmd.com/read/28292439/integrated-molecular-characterization-of-uterine-carcinosarcoma
#3
Andrew D Cherniack, Hui Shen, Vonn Walter, Chip Stewart, Bradley A Murray, Reanne Bowlby, Xin Hu, Shiyun Ling, Robert A Soslow, Russell R Broaddus, Rosemary E Zuna, Gordon Robertson, Peter W Laird, Raju Kucherlapati, Gordon B Mills, John N Weinstein, Jiashan Zhang, Rehan Akbani, Douglas A Levine
We performed genomic, epigenomic, transcriptomic, and proteomic characterizations of uterine carcinosarcomas (UCSs). Cohort samples had extensive copy-number alterations and highly recurrent somatic mutations. Frequent mutations were found in TP53, PTEN, PIK3CA, PPP2R1A, FBXW7, and KRAS, similar to endometrioid and serous uterine carcinomas. Transcriptome sequencing identified a strong epithelial-to-mesenchymal transition (EMT) gene signature in a subset of cases that was attributable to epigenetic alterations at microRNA promoters...
March 13, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28289945/a-novel-representation-of-inter-site-tumour-heterogeneity-from-pre-treatment-computed-tomography-textures-classifies-ovarian-cancers-by-clinical-outcome
#4
Hebert Alberto Vargas, Harini Veeraraghavan, Maura Micco, Stephanie Nougaret, Yulia Lakhman, Andreas A Meier, Ramon Sosa, Robert A Soslow, Douglas A Levine, Britta Weigelt, Carol Aghajanian, Hedvig Hricak, Joseph Deasy, Alexandra Snyder, Evis Sala
PURPOSE: To evaluate the associations between clinical outcomes and radiomics-derived inter-site spatial heterogeneity metrics across multiple metastatic lesions on CT in patients with high-grade serous ovarian cancer (HGSOC). METHODS: IRB-approved retrospective study of 38 HGSOC patients. All sites of suspected HGSOC involvement on preoperative CT were manually segmented. Gray-level correlation matrix-based textures were computed from each tumour site, and grouped into five clusters using a Gaussian Mixture Model...
March 13, 2017: European Radiology
https://www.readbyqxmd.com/read/28267263/genetic-analysis-of-uterine-adenosarcomas-and-phyllodes-tumors-of-the-breast
#5
Felipe C Geyer, Kathleen A Burke, Salvatore Piscuoglio, Charlotte K Y Ng, Anastasios D Papanastasiou, Caterina Marchiò, Pier Selenica, Marcia Edelweiss, Melissa P Murray, Edi Brogi, Robert A Soslow, Brian P Rubin, Larry Norton, Jorge S Reis-Filho, Britta Weigelt
Uterine adenosarcomas and breast phyllodes tumors (PTs) are morphologically similar, being composed of stromal projections in a leaf-like fashion lined by epithelial cells. Here we investigated whether their histologic similarities would be mirrored at the genetic level. The previously reported repertoires of somatic genetic alterations found in 19 adenosarcomas and 22 PTs (six benign, six borderline and 10 malignant) were compared. Phyllodes tumors significantly more frequently displayed mutations affecting MED12, the TERT gene promoter and bona fide cancer genes; whereas adenosarcomas harbored a higher rate of MDM2/CDK4 and TERT gene amplifications...
March 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28258415/survival-of-patients-with-serous-uterine-carcinoma-undergoing-sentinel-lymph-node-mapping
#6
Maria B Schiavone, Chiara Scelzo, Celeste Straight, Qin Zhou, Kaled M Alektiar, Vicky Makker, Robert A Soslow, Alexia Iasonos, Mario M Leitao, Nadeem R Abu-Rustum
OBJECTIVE: The aim of this study was to determine progression-free survival (PFS) in patients with serous uterine carcinoma undergoing sentinel lymph node (SLN) mapping compared with patients undergoing standard lymphadenectomy. METHODS: We retrospectively reviewed all uterine cancer patients treated at our institution from 2005 to 2015. Patients were separated into two cohorts: those who underwent SLN mapping at the time of staging (SLN) and those who underwent routine lymphadenectomy (the non-SLN group)...
March 3, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28221217/interobserver-reproducibility-among-gynecologic-pathologists-in-diagnosing-heterologous-osteosarcomatous-component-in-gynecologic-tract-carcinosarcomas
#7
Ankur R Sangoi, Malti Kshirsagar, Andres A Roma, Andrew E Horvai, Mamatha Chivukula, Lora H Ellenson, Oluwole Fadare, Ann K Folkins, Karuna Garg, Krisztina Hanley, Teri A Longacre, Jacqueline Haas, W Glenn McCluggage, Jesse K McKenney, Marisa R Nucci, Esther Oliva, Kay J Park, Vinita Parkash, Charles M Quick, Joseph T Rabban, Joanne K L Rutgers, Robert Soslow, Russell Vang, Anna Yemelyanova, Charles Zaloudek, Andrew H Beck
Distinguishing hyalinized stroma from osteoid production by a heterologous osteosarcomatous component can be challenging in gynecologic tract carcinosarcomas. As heterologous components in a carcinosarcoma may have prognostic and therapeutic implications, it is important that these are recognized. This study examines interobserver reproducibility among gynecologic pathologists in the diagnosis of osteosarcomatous components, and its correlation with expression of the novel antibody SATB2 (marker of osteoblastic differentiation) in these osteosarcomatous foci...
February 17, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28114191/frequent-mismatch-repair-protein-deficiency-in-mixed-endometrioid-and-clear-cell-carcinoma-of-the-endometrium
#8
Martin Köbel, Basile Tessier-Cloutier, Joyce Leo, Lien N Hoang, C Blake Gilks, Robert A Soslow, Deborah Delair, Colin J R Stewart, Cheng-Han Lee
Mixed endometrioid and clear cell carcinoma of the endometrium refers to a scenario in which the tumor exhibits histologic features of both endometrioid and clear cell carcinoma. We observed a tendency for these tumors to occur in a mismatch repair (MMR) protein-deficient molecular background in a prior study that examined a small cohort of mixed-type endometrial carcinomas. The aim of this study was to determine the rate of MMR protein deficiency in a larger series of endometrial mixed endometrioid and clear cell carcinomas, through a retrospective survey of MLH1, PMS2, MSH2, and MSH6 expression in such tumors at 5 tertiary centers...
January 20, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/28097235/a-patient-derived-xenograft-platform-to-study-brca-deficient-ovarian-cancers
#9
Erin George, Hyoung Kim, Clemens Krepler, Brandon Wenz, Mehran Makvandi, Janos L Tanyi, Eric Brown, Rugang Zhang, Patricia Brafford, Stephanie Jean, Robert H Mach, Yiling Lu, Gordon B Mills, Meenhard Herlyn, Mark Morgan, Xiaochen Zhang, Robert Soslow, Ronny Drapkin, Neil Johnson, Ying Zheng, George Cotsarelis, Katherine L Nathanson, Fiona Simpkins
Approximately 50% of high-grade serous ovarian cancers (HGSOCs) have defects in genes involved in homologous recombination (HR) (i.e., BRCA1/2). Preclinical models to optimize therapeutic strategies for HR-deficient (HRD) HGSOC are lacking. We developed a preclinical platform for HRD HGSOCs that includes primary tumor cultures, patient-derived xenografts (PDXs), and molecular imaging. Models were characterized by immunohistochemistry, targeted sequencing, and reverse-phase protein array analysis. We also tested PDX tumor response to PARP, CHK1, and ATR inhibitors...
January 12, 2017: JCI Insight
https://www.readbyqxmd.com/read/28079598/interobserver-agreement-in-endometrial-carcinoma-histotype-diagnosis-varies-depending-on-the-cancer-genome-atlas-tcga-based-molecular-subgroup
#10
Lien N Hoang, Mary A Kinloch, Joyce M Leo, Katherine Grondin, Cheng-Han Lee, Carol Ewanowich, Martin Köbel, Angela Cheng, Aline Talhouk, Melissa McConechy, David G Huntsman, Jessica N McAlpine, Robert A Soslow, C Blake Gilks
The Cancer Genome Atlas recently identified a genomic-based molecular classification of endometrial carcinomas, with 4 molecular categories: (1) ultramutated (polymerase epsilon [POLE] mutated), (2) hypermutated (microsatellite instability), (3) copy number abnormalities-low, and (4) copy number abnormalities-high. Two studies have since proposed models to classify endometrial carcinomas into 4 molecular subgroups, modeled after The Cancer Genome Atlas, using simplified and more clinically applicable surrogate methodologies...
February 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28004137/abdominal-wall-endometriosis-differentiation-from-other-masses-using-ct-features
#11
Gail Yarmish, Evis Sala, Debra A Goldman, Yulia Lakhman, Robert A Soslow, Hedvig Hricak, Ginger J Gardner, H Alberto Vargas
PURPOSE: To assess the utility of morphologic and quantitative CT features in differentiating abdominal wall endometriosis (AWE) from other masses of the abdominal wall. METHODS: Retrospective IRB-approved study of 105 consecutive women from two institutions who underwent CT and biopsy/resection of abdominal wall masses. CTs were independently reviewed by two radiologists blinded to final histopathologic diagnoses. Associations between CT features and pathology were tested using Fisher's Exact Test...
December 21, 2016: Abdominal Radiology
https://www.readbyqxmd.com/read/27921159/differentiation-of-uterine-leiomyosarcoma-from-atypical-leiomyoma-diagnostic-accuracy-of-qualitative-mr-imaging-features-and-feasibility-of-texture-analysis
#12
Yulia Lakhman, Harini Veeraraghavan, Joshua Chaim, Diana Feier, Debra A Goldman, Chaya S Moskowitz, Stephanie Nougaret, Ramon E Sosa, Hebert Alberto Vargas, Robert A Soslow, Nadeem R Abu-Rustum, Hedvig Hricak, Evis Sala
PURPOSE: To investigate whether qualitative magnetic resonance (MR) features can distinguish leiomyosarcoma (LMS) from atypical leiomyoma (ALM) and assess the feasibility of texture analysis (TA). METHODS: This retrospective study included 41 women (ALM = 22, LMS = 19) imaged with MRI prior to surgery. Two readers (R1, R2) evaluated each lesion for qualitative MR features. Associations between MR features and LMS were evaluated with Fisher's exact test. Accuracy measures were calculated for the four most significant features...
December 5, 2016: European Radiology
https://www.readbyqxmd.com/read/27895324/molecular-genetic-heterogeneity-in-undifferentiated-endometrial-carcinomas
#13
Juan M Rosa-Rosa, Susanna Leskelä, Eva Cristóbal-Lana, Almudena Santón, Ma Ángeles López-García, Gloria Muñoz, Belen Pérez-Mies, Michele Biscuola, Jaime Prat, Oliva E Esther, Robert A Soslow, Xavier Matias-Guiu, Jose Palacios
No abstract text is available yet for this article.
December 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27636886/mature-and-immature-solid-teratomas-involving-uterine-corpus-cervix-and-ovary
#14
Simona Stolnicu, Emoke Szekely, Calin Molnar, Claudiu V Molnar, Iulia Barsan, Valeria D'Alfonso, Cosmin Moldovan, Gang Zheng, Brigitte M Ronnett, Robert A Soslow
Extragonadal teratomas are rare, and localization in the endometrium and cervix is exceptional, with fewer than 10 case reports documented so far in the English literature. We report here the case of a 46-year-old patient who presented with simultaneous immature teratoma in the endometrium and mature teratomas in the ovary in association with gliomatosis peritonei but with no evidence of gestational origin; she subsequently developed multiple solid mature teratomas in the cervix and parauterine tissue. No other similar cases have been previously reported to our knowledge...
September 15, 2016: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/27631520/novel-high-grade-endometrial-stromal-sarcoma-a-morphologic-mimicker-of-myxoid-leiomyosarcoma
#15
Lien N Hoang, Amandeep Aneja, Niamh Conlon, Deborah F Delair, Sumit Middha, Ryma Benayed, Martee L Hensley, Kay J Park, Travis J Hollmann, Meera R Hameed, Cristina R Antonescu, Robert A Soslow, Sarah Chiang
Endometrial stromal sarcomas (ESS) are often underpinned by recurrent chromosomal translocations resulting in the fusion of genes involved in epigenetic regulation. To date, only YWHAE-NUTM2 rearrangements are associated with distinctive high-grade morphology and aggressive clinical behavior. We identified 3 ESS morphologically mimicking myxoid leiomyosarcoma of the uterus and sought to describe their unique histopathologic features and identify genetic alterations using next-generation sequencing. All cases displayed predominantly spindled cells associated with abundant myxoid stroma and brisk mitotic activity...
January 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27562491/concurrent-arid1a-and-arid1b-inactivation-in-endometrial-and-ovarian-dedifferentiated-carcinomas
#16
Mackenzie Coatham, Xiaodong Li, Anthony N Karnezis, Lien N Hoang, Basile Tessier-Cloutier, Bo Meng, Robert A Soslow, C Blake Gilks, David G Huntsman, Colin J R Stewart, Lynne M Postovit, Martin Köbel, Cheng-Han Lee
Dedifferentiated carcinoma of the endometrium or the ovary is an aggressive epithelial malignancy that comprises an endometrioid carcinoma together with an undifferentiated carcinoma. We recently reported that inactivation of BRG1 or INI1, core subunits of the switch/sucrose non-fermenting (SWI/SNF) complex, was the likely molecular event underlying dedifferentiation in about half of dedifferentiated carcinomas. In this study, we performed a genomic screen that included other members of the SWI/SNF complex to better delineate the molecular basis in the remainder of these tumours...
August 26, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27526294/the-2015-fred-waldorf-stewart-award-recipient-robert-h-young-md
#17
Robert A Soslow, Edi Brogi
No abstract text is available yet for this article.
August 11, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27491810/molecular-genetic-heterogeneity-in-undifferentiated-endometrial-carcinomas
#18
Juan M Rosa-Rosa, Susanna Leskelä, Eva Cristóbal-Lana, Almudena Santón, Ma Ángeles López-García, Gloria Muñoz, Belen Pérez-Mies, Michele Biscuola, Jaime Prat, Oliva E Esther, Robert A Soslow, Xavier Matias-Guiu, Jose Palacios
Undifferentiated and dedifferentiated endometrial carcinomas are rare and highly aggressive subtypes of uterine cancer, not well characterized at a molecular level. To investigate whether dedifferentiated carcinomas carry molecular genetic alterations similar to those of pure undifferentiated carcinomas, and to gain insight into the pathogenesis of these tumors, we selected a cohort of 18 undifferentiated endometrial carcinomas, 8 of them with a well-differentiated endometrioid carcinoma component (dedifferentiated endometrioid carcinomas), and studied them by immunohistochemistry and massive parallel and Sanger sequencing...
August 5, 2016: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/27421752/molecular-classification-of-endometrial-carcinoma-on-diagnostic-specimens-is-highly-concordant-with-final-hysterectomy-earlier-prognostic-information-to-guide-treatment
#19
Aline Talhouk, Lien N Hoang, Melissa K McConechy, Quentin Nakonechny, Joyce Leo, Angela Cheng, Samuel Leung, Winnie Yang, Amy Lum, Martin Köbel, Cheng-Han Lee, Robert A Soslow, David G Huntsman, C Blake Gilks, Jessica N McAlpine
OBJECTIVE: Categorization and risk stratification of endometrial carcinomas is inadequate; histomorphologic assessment shows considerable interobserver variability, and risk of metastases and recurrence can only be derived after surgical staging. We have developed a Proactive Molecular Risk classification tool for Endometrial cancers (ProMisE) that identifies four distinct prognostic subgroups. Our objective was to assess whether molecular classification could be performed on diagnostic endometrial specimens obtained prior to surgical staging and its concordance with molecular classification performed on the subsequent hysterectomy specimen...
October 2016: Gynecologic Oncology
https://www.readbyqxmd.com/read/27367496/uterine-cancer-after-risk-reducing-salpingo-oophorectomy-without-hysterectomy-in-women-with-brca-mutations
#20
MULTICENTER STUDY
Catherine A Shu, Malcolm C Pike, Anjali R Jotwani, Tara M Friebel, Robert A Soslow, Douglas A Levine, Katherine L Nathanson, Jason A Konner, Angela G Arnold, Faina Bogomolniy, Fanny Dao, Narciso Olvera, Elizabeth K Bancroft, Deborah J Goldfrank, Zsofia K Stadler, Mark E Robson, Carol L Brown, Mario M Leitao, Nadeem R Abu-Rustum, Carol A Aghajanian, Joanne L Blum, Susan L Neuhausen, Judy E Garber, Mary B Daly, Claudine Isaacs, Rosalind A Eeles, Patricia A Ganz, Richard R Barakat, Kenneth Offit, Susan M Domchek, Timothy R Rebbeck, Noah D Kauff
Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial. Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy. Design, Setting, and Participants: This multicenter prospective cohort study included 1083 women with a deleterious BRCA1 or BRCA2 mutation identified from January 1, 1995, to December 31, 2011, at 9 academic medical centers in the United States and the United Kingdom who underwent RRSO without a prior or concomitant hysterectomy...
November 1, 2016: JAMA Oncology
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