PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer. EXPERIMENTAL DESIGN: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated. RESULTS: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers. CONCLUSIONS: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.
PURPOSE: Germline mutations in the BRCA1 and BRCA2 genes confer increased susceptibility to ovarian cancer. There is evidence that tumors in carriers may exhibit a distinct distribution of pathological features, but previous studies on the pathology of such tumors have been small. Our aim was to evaluate the morphologies and immunophenotypes in a large cohort of patients with familial ovarian cancer. EXPERIMENTAL DESIGN: We performed a systematic review of ovarian tumors from 178 BRCA1 mutation carriers, 29 BRCA2 mutation carriers, and 235 controls with a similar age distribution. Tumors were evaluated by four pathologists blinded to mutation status. Both morphological features and immunochemical staining for p53 and HER2 were evaluated. RESULTS: Tumors in BRCA1 mutation carriers were more likely than tumors in age-matched controls to be invasive serous adenocarcinomas (odds ratio, 1.84; 95% confidence interval, 1.21-2.79) and unlikely to be borderline or mucinous tumors. Tumors in BRCA1 carriers were of higher grade (P < 0.0001), had a higher percentage solid component (P = 0.001), and were more likely to stain strongly for p53 (P = 0.018). The distribution of pathological features in BRCA2 carriers was similar to that in BRCA1 carriers. CONCLUSIONS: Use of pathological features can substantially improve the targeting of predictive genetic testing. Results also suggest that BRCA1 and BRCA2 tumors are relatively aggressive and may be expected to have poor prognosis, although this may be treatment dependent.
Authors: Nasim Mavaddat; Daniel Barrowdale; Irene L Andrulis; Susan M Domchek; Diana Eccles; Heli Nevanlinna; Susan J Ramus; Amanda Spurdle; Mark Robson; Mark Sherman; Anna Marie Mulligan; Fergus J Couch; Christoph Engel; Lesley McGuffog; Sue Healey; Olga M Sinilnikova; Melissa C Southey; Mary Beth Terry; David Goldgar; Frances O'Malley; Esther M John; Ramunas Janavicius; Laima Tihomirova; Thomas V O Hansen; Finn C Nielsen; Ana Osorio; Alexandra Stavropoulou; Javier Benítez; Siranoush Manoukian; Bernard Peissel; Monica Barile; Sara Volorio; Barbara Pasini; Riccardo Dolcetti; Anna Laura Putignano; Laura Ottini; Paolo Radice; Ute Hamann; Muhammad U Rashid; Frans B Hogervorst; Mieke Kriege; Rob B van der Luijt; Susan Peock; Debra Frost; D Gareth Evans; Carole Brewer; Lisa Walker; Mark T Rogers; Lucy E Side; Catherine Houghton; JoEllen Weaver; Andrew K Godwin; Rita K Schmutzler; Barbara Wappenschmidt; Alfons Meindl; Karin Kast; Norbert Arnold; Dieter Niederacher; Christian Sutter; Helmut Deissler; Doroteha Gadzicki; Sabine Preisler-Adams; Raymonda Varon-Mateeva; Ines Schönbuchner; Heidrun Gevensleben; Dominique Stoppa-Lyonnet; Muriel Belotti; Laure Barjhoux; Claudine Isaacs; Beth N Peshkin; Trinidad Caldes; Miguel de la Hoya; Carmen Cañadas; Tuomas Heikkinen; Päivi Heikkilä; Kristiina Aittomäki; Ignacio Blanco; Conxi Lazaro; Joan Brunet; Bjarni A Agnarsson; Adalgeir Arason; Rosa B Barkardottir; Martine Dumont; Jacques Simard; Marco Montagna; Simona Agata; Emma D'Andrea; Max Yan; Stephen Fox; Timothy R Rebbeck; Wendy Rubinstein; Nadine Tung; Judy E Garber; Xianshu Wang; Zachary Fredericksen; Vernon S Pankratz; Noralane M Lindor; Csilla Szabo; Kenneth Offit; Rita Sakr; Mia M Gaudet; Christian F Singer; Muy-Kheng Tea; Christine Rappaport; Phuong L Mai; Mark H Greene; Anna Sokolenko; Evgeny Imyanitov; Amanda Ewart Toland; Leigha Senter; Kevin Sweet; Mads Thomassen; Anne-Marie Gerdes; Torben Kruse; Maria Caligo; Paolo Aretini; Johanna Rantala; Anna von Wachenfeld; Karin Henriksson; Linda Steele; Susan L Neuhausen; Robert Nussbaum; Mary Beattie; Kunle Odunsi; Lara Sucheston; Simon A Gayther; Kate Nathanson; Jenny Gross; Christine Walsh; Beth Karlan; Georgia Chenevix-Trench; Douglas F Easton; Antonis C Antoniou Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-12-05 Impact factor: 4.254
Authors: Kelly L Bolton; Georgia Chenevix-Trench; Cindy Goh; Siegal Sadetzki; Susan J Ramus; Beth Y Karlan; Diether Lambrechts; Evelyn Despierre; Daniel Barrowdale; Lesley McGuffog; Sue Healey; Douglas F Easton; Olga Sinilnikova; Javier Benítez; María J García; Susan Neuhausen; Mitchell H Gail; Patricia Hartge; Susan Peock; Debra Frost; D Gareth Evans; Rosalind Eeles; Andrew K Godwin; Mary B Daly; Ava Kwong; Edmond S K Ma; Conxi Lázaro; Ignacio Blanco; Marco Montagna; Emma D'Andrea; Maria Ornella Nicoletto; Sharon E Johnatty; Susanne Krüger Kjær; Allan Jensen; Estrid Høgdall; Ellen L Goode; Brooke L Fridley; Jennifer T Loud; Mark H Greene; Phuong L Mai; Angela Chetrit; Flora Lubin; Galit Hirsh-Yechezkel; Gord Glendon; Irene L Andrulis; Amanda E Toland; Leigha Senter; Martin E Gore; Charlie Gourley; Caroline O Michie; Honglin Song; Jonathan Tyrer; Alice S Whittemore; Valerie McGuire; Weiva Sieh; Ulf Kristoffersson; Håkan Olsson; Åke Borg; Douglas A Levine; Linda Steele; Mary S Beattie; Salina Chan; Robert L Nussbaum; Kirsten B Moysich; Jenny Gross; Ilana Cass; Christine Walsh; Andrew J Li; Ronald Leuchter; Ora Gordon; Montserrat Garcia-Closas; Simon A Gayther; Stephen J Chanock; Antonis C Antoniou; Paul D P Pharoah Journal: JAMA Date: 2012-01-25 Impact factor: 56.272
Authors: Barbara M Norquist; Kathryn P Pennington; Kathy J Agnew; Maria I Harrell; Christopher C Pennil; Ming K Lee; Silvia Casadei; Anne M Thornton; Rochelle L Garcia; Tom Walsh; Elizabeth M Swisher Journal: Gynecol Oncol Date: 2012-12-19 Impact factor: 5.482
Authors: Mika Fujiwara; Valerie A McGuire; Anna Felberg; Weiva Sieh; Alice S Whittemore; Teri A Longacre Journal: Am J Surg Pathol Date: 2012-08 Impact factor: 6.394
Authors: L Quaye; H Song; S J Ramus; A Gentry-Maharaj; E Høgdall; R A DiCioccio; V McGuire; A H Wu; D J Van Den Berg; M C Pike; E Wozniak; J A Doherty; M A Rossing; R B Ness; K B Moysich; C Høgdall; J Blaakaer; D F Easton; B A J Ponder; I J Jacobs; U Menon; A S Whittemore; S Krüger-Kjaer; C L Pearce; P D P Pharoah; S A Gayther Journal: Br J Cancer Date: 2009-02-24 Impact factor: 7.640