PURPOSE: Parathyroid hormone-related protein (PTHRP) is in part responsible for the clinical syndrome of hypercalcaemia of malignancy and has been implicated as an important factor in the development of bone metastases. The aim of this study was to determine the coexpression of PTHRP and its receptor in early breast cancer (EBC) and bone metastases (BM), and correlate these findings to clinical outcome. EXPERIMENTAL DESIGN: Samples of surgically excised EBC (n = 176) and BM (n = 43) were collected and stored in liquid nitrogen. PTHRP protein was determined using immunohistochemistry and receptor mRNA using in situ hybridization (n = 107) or semiquantitative reverse transcription-PCR (n = 69). RESULTS: PTHRP protein was expressed in 115 of 170 (68%) EBC compared with 100% of BM (P < 0.001), whereas its receptor mRNA was expressed in 88 of 176 (50%) EBC compared with 35 of 43 (81%) BM (P < 0.001). Coexpression of both PTHRP and its receptor was present in 62 EBC samples (37%) and in 35 BM samples (81%; P < 0.001). The PTHRP receptor correlated well with increasing patient age, but not with tumor size, grade, estrogen receptor, progesterone receptor, or lymph node status. Individually PTHRP and PTHRP receptor both correlated well with a reduced disease-free survival (P < 0.004) and receptor alone with reduced overall survival (P < 0.003). Coexpression of both PTHRP and receptor predicted the worst clinical outcome at 5 years, with a mortality rate of 20 of 62 (32%) compared with the ligand and receptor-negative group with 2 of 32 (6%; P < 0.004). CONCLUSIONS: Overall these results show that the PTHRP receptor is expressed more frequently in BM than EBC, and is associated with poor clinical outcome and survival.
PURPOSE:Parathyroid hormone-related protein (PTHRP) is in part responsible for the clinical syndrome of hypercalcaemia of malignancy and has been implicated as an important factor in the development of bone metastases. The aim of this study was to determine the coexpression of PTHRP and its receptor in early breast cancer (EBC) and bone metastases (BM), and correlate these findings to clinical outcome. EXPERIMENTAL DESIGN: Samples of surgically excised EBC (n = 176) and BM (n = 43) were collected and stored in liquid nitrogen. PTHRP protein was determined using immunohistochemistry and receptor mRNA using in situ hybridization (n = 107) or semiquantitative reverse transcription-PCR (n = 69). RESULTS:PTHRP protein was expressed in 115 of 170 (68%) EBC compared with 100% of BM (P < 0.001), whereas its receptor mRNA was expressed in 88 of 176 (50%) EBC compared with 35 of 43 (81%) BM (P < 0.001). Coexpression of both PTHRP and its receptor was present in 62 EBC samples (37%) and in 35 BM samples (81%; P < 0.001). The PTHRP receptor correlated well with increasing patient age, but not with tumor size, grade, estrogen receptor, progesterone receptor, or lymph node status. Individually PTHRP and PTHRP receptor both correlated well with a reduced disease-free survival (P < 0.004) and receptor alone with reduced overall survival (P < 0.003). Coexpression of both PTHRP and receptor predicted the worst clinical outcome at 5 years, with a mortality rate of 20 of 62 (32%) compared with the ligand and receptor-negative group with 2 of 32 (6%; P < 0.004). CONCLUSIONS: Overall these results show that the PTHRP receptor is expressed more frequently in BM than EBC, and is associated with poor clinical outcome and survival.
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Authors: Maya Ghoussaini; Olivia Fletcher; Kyriaki Michailidou; Clare Turnbull; Marjanka K Schmidt; Ed Dicks; Joe Dennis; Qin Wang; Manjeet K Humphreys; Craig Luccarini; Caroline Baynes; Don Conroy; Melanie Maranian; Shahana Ahmed; Kristy Driver; Nichola Johnson; Nicholas Orr; Isabel dos Santos Silva; Quinten Waisfisz; Hanne Meijers-Heijboer; Andre G Uitterlinden; Fernando Rivadeneira; Per Hall; Kamila Czene; Astrid Irwanto; Jianjun Liu; Heli Nevanlinna; Kristiina Aittomäki; Carl Blomqvist; Alfons Meindl; Rita K Schmutzler; Bertram Müller-Myhsok; Peter Lichtner; Jenny Chang-Claude; Rebecca Hein; Stefan Nickels; Dieter Flesch-Janys; Helen Tsimiklis; Enes Makalic; Daniel Schmidt; Minh Bui; John L Hopper; Carmel Apicella; Daniel J Park; Melissa Southey; David J Hunter; Stephen J Chanock; Annegien Broeks; Senno Verhoef; Frans B L Hogervorst; Peter A Fasching; Michael P Lux; Matthias W Beckmann; Arif B Ekici; Elinor Sawyer; Ian Tomlinson; Michael Kerin; Frederik Marme; Andreas Schneeweiss; Christof Sohn; Barbara Burwinkel; Pascal Guénel; Thérèse Truong; Emilie Cordina-Duverger; Florence Menegaux; Stig E Bojesen; Børge G Nordestgaard; Sune F Nielsen; Henrik Flyger; Roger L Milne; M Rosario Alonso; Anna González-Neira; Javier Benítez; Hoda Anton-Culver; Argyrios Ziogas; Leslie Bernstein; Christina Clarke Dur; Hermann Brenner; Heiko Müller; Volker Arndt; Christa Stegmaier; Christina Justenhoven; Hiltrud Brauch; Thomas Brüning; Shan Wang-Gohrke; Ursula Eilber; Thilo Dörk; Peter Schürmann; Michael Bremer; Peter Hillemanns; Natalia V Bogdanova; Natalia N Antonenkova; Yuri I Rogov; Johann H Karstens; Marina Bermisheva; Darya Prokofieva; Elza Khusnutdinova; Annika Lindblom; Sara Margolin; Arto Mannermaa; Vesa Kataja; Veli-Matti Kosma; Jaana M Hartikainen; Diether Lambrechts; Betul T Yesilyurt; Giuseppe Floris; Karin Leunen; Siranoush Manoukian; Bernardo Bonanni; Stefano Fortuzzi; Paolo Peterlongo; Fergus J Couch; Xianshu Wang; Kristen Stevens; Adam Lee; Graham G Giles; Laura Baglietto; Gianluca Severi; Catriona McLean; Grethe Grenaker Alnaes; Vessela Kristensen; Anne-Lise Børrensen-Dale; Esther M John; Alexander Miron; Robert Winqvist; Katri Pylkäs; Arja Jukkola-Vuorinen; Saila Kauppila; Irene L Andrulis; Gord Glendon; Anna Marie Mulligan; Peter Devilee; Christie J van Asperen; Rob A E M Tollenaar; Caroline Seynaeve; Jonine D Figueroa; Montserrat Garcia-Closas; Louise Brinton; Jolanta Lissowska; Maartje J Hooning; Antoinette Hollestelle; Rogier A Oldenburg; Ans M W van den Ouweland; Angela Cox; Malcolm W R Reed; Mitul Shah; Ania Jakubowska; Jan Lubinski; Katarzyna Jaworska; Katarzyna Durda; Michael Jones; Minouk Schoemaker; Alan Ashworth; Anthony Swerdlow; Jonathan Beesley; Xiaoqing Chen; Kenneth R Muir; Artitaya Lophatananon; Suthee Rattanamongkongul; Arkom Chaiwerawattana; Daehee Kang; Keun-Young Yoo; Dong-Young Noh; Chen-Yang Shen; Jyh-Cherng Yu; Pei-Ei Wu; Chia-Ni Hsiung; Annie Perkins; Ruth Swann; Louiza Velentzis; Diana M Eccles; Will J Tapper; Susan M Gerty; Nikki J Graham; Bruce A J Ponder; Georgia Chenevix-Trench; Paul D P Pharoah; Mark Lathrop; Alison M Dunning; Nazneen Rahman; Julian Peto; Douglas F Easton Journal: Nat Genet Date: 2012-01-22 Impact factor: 38.330
Authors: Antonis C Antoniou; Karoline B Kuchenbaecker; Penny Soucy; Jonathan Beesley; Xiaoqing Chen; Lesley McGuffog; Andrew Lee; Daniel Barrowdale; Sue Healey; Olga M Sinilnikova; Maria A Caligo; Niklas Loman; Katja Harbst; Annika Lindblom; Brita Arver; Richard Rosenquist; Per Karlsson; Kate Nathanson; Susan Domchek; Tim Rebbeck; Anna Jakubowska; Jan Lubinski; Katarzyna Jaworska; Katarzyna Durda; Elżbieta Złowowcka-Perłowska; Ana Osorio; Mercedes Durán; Raquel Andrés; Javier Benítez; Ute Hamann; Frans B Hogervorst; Theo A van Os; Senno Verhoef; Hanne E J Meijers-Heijboer; Juul Wijnen; Encarna B Gómez Garcia; Marjolijn J Ligtenberg; Mieke Kriege; J Margriet Collée; Margreet G E M Ausems; Jan C Oosterwijk; Susan Peock; Debra Frost; Steve D Ellis; Radka Platte; Elena Fineberg; D Gareth Evans; Fiona Lalloo; Chris Jacobs; Ros Eeles; Julian Adlard; Rosemarie Davidson; Trevor Cole; Jackie Cook; Joan Paterson; Fiona Douglas; Carole Brewer; Shirley Hodgson; Patrick J Morrison; Lisa Walker; Mark T Rogers; Alan Donaldson; Huw Dorkins; Andrew K Godwin; Betsy Bove; Dominique Stoppa-Lyonnet; Claude Houdayer; Bruno Buecher; Antoine de Pauw; Sylvie Mazoyer; Alain Calender; Mélanie Léoné; Brigitte Bressac-de Paillerets; Olivier Caron; Hagay Sobol; Marc Frenay; Fabienne Prieur; Sandra U Ferrer; Isabelle Mortemousque; Saundra Buys; Mary Daly; Alexander Miron; Mary U Terry; John L Hopper; Esther M John; Melissa Southey; David Goldgar; Christian F Singer; Anneliese Fink-Retter; Muy-Kheng Tea; Daphne U Kaulich; Thomas V Hansen; Finn C Nielsen; Rosa B Barkardottir; Mia Gaudet; Tomas Kirchhoff; Vijai Joseph; Ana Dutra-Clarke; Kenneth Offit; Marion Piedmonte; Judy Kirk; David Cohn; Jean Hurteau; John Byron; James Fiorica; Amanda E Toland; Marco Montagna; Cristina Oliani; Evgeny Imyanitov; Claudine Isaacs; Laima Tihomirova; Ignacio Blanco; Conxi Lazaro; Alex Teulé; J Del Valle; Simon A Gayther; Kunle Odunsi; Jenny Gross; Beth Y Karlan; Edith Olah; Soo-Hwang Teo; Patricia A Ganz; Mary S Beattie; Cecelia M Dorfling; Elizabeth U van Rensburg; Orland Diez; Ava Kwong; Rita K Schmutzler; Barbara Wappenschmidt; Christoph Engel; Alfons Meindl; Nina Ditsch; Norbert Arnold; Simone Heidemann; Dieter Niederacher; Sabine Preisler-Adams; Dorothea Gadzicki; Raymonda Varon-Mateeva; Helmut Deissler; Andrea Gehrig; Christian Sutter; Karin Kast; Britta Fiebig; Dieter Schäfer; Trinidad Caldes; Miguel de la Hoya; Heli Nevanlinna; Taru A Muranen; Bernard Lespérance; Amanda B Spurdle; Susan L Neuhausen; Yuan C Ding; Xianshu Wang; Zachary Fredericksen; Vernon S Pankratz; Noralane M Lindor; Paolo Peterlongo; Siranoush Manoukian; Bernard Peissel; Daniela Zaffaroni; Bernardo Bonanni; Loris Bernard; Riccardo Dolcetti; Laura Papi; Laura Ottini; Paolo Radice; Mark H Greene; Jennifer T Loud; Irene L Andrulis; Hilmi Ozcelik; Anna U Mulligan; Gord Glendon; Mads Thomassen; Anne-Marie Gerdes; Uffe B Jensen; Anne-Bine Skytte; Torben A Kruse; Georgia Chenevix-Trench; Fergus J Couch; Jacques Simard; Douglas F Easton Journal: Breast Cancer Res Date: 2012-02-20 Impact factor: 6.466