T J A Dekker1, A Charehbili1, V T H B M Smit2, P ten Dijke3, E Meershoek-Klein Kranenbarg4, C J H van de Velde4, J W R Nortier5, R A E M Tollenaar4, W E Mesker4, J R Kroep6. 1. Department of Clinical Oncology, Leiden University Medical Center, The Netherlands; Department of Surgery, Leiden University Medical Center, The Netherlands. 2. Department of Pathology, Leiden University Medical Center, The Netherlands. 3. Department of Molecular Cell Biology and Cancer Genomics Centre Netherlands, Leiden University Medical Center, The Netherlands; Ludwig Institute for Cancer Research, Uppsala, Sweden. 4. Department of Surgery, Leiden University Medical Center, The Netherlands. 5. Department of Clinical Oncology, Leiden University Medical Center, The Netherlands. 6. Department of Clinical Oncology, Leiden University Medical Center, The Netherlands. Electronic address: j.r.kroep@lumc.nl.
Abstract
INTRODUCTION: The tumor-associated stroma is of importance for tumor progression and is generally accepted to have a significant influence on patient prognosis. However, little is known regarding specific features of tumor-associated stromal tissues and response to (neoadjuvant) chemotherapy. This study investigated the predictive value of extracellular matrix organization on response to chemotherapy in patients treated in the NEOZOTAC trial. METHODS: Stromal organisation was analyzed via a simple method using image analysis software on hematoxylin and eosin (H&E)-stained slides from primary tumor biopsies collected as part of the NEOZOTAC trial. Heidenhain's AZAN trichrome-stained slides were also analyzed for comparison of collagen evaluation. Sections were stained for phospho-Smad2 (pS2) in order to determine the relationship of TGF-β signaling with stromal organization. RESULTS: A statistically significant relationship was observed between stroma consisting of organised collagen and pathological response to neoadjuvant chemotherapy (Odds Ratio 0.276, 95%CI 0.124-0.614, P = 0.002). This parameter was also related to ER-status (P = 0.003), clinical tumor -status (P = 0.041), nodal status (P = 0.029) and pS2 status (P = 0.025). Correlation between stromal organisation determined on H&E-stained and AZAN-stained tissue sections was high (Pearson's correlation coefficient = 0.806). CONCLUSION:Intratumoral stromal organisation determined using pre-treatment breast cancer biopsies was related to pathological response to chemotherapy. This parameter might play a role in the management of breast cancer for identifying those patients that are likely to benefit from neoadjuvant chemotherapy.
RCT Entities:
INTRODUCTION: The tumor-associated stroma is of importance for tumor progression and is generally accepted to have a significant influence on patient prognosis. However, little is known regarding specific features of tumor-associated stromal tissues and response to (neoadjuvant) chemotherapy. This study investigated the predictive value of extracellular matrix organization on response to chemotherapy in patients treated in the NEOZOTAC trial. METHODS: Stromal organisation was analyzed via a simple method using image analysis software on hematoxylin and eosin (H&E)-stained slides from primary tumor biopsies collected as part of the NEOZOTAC trial. Heidenhain's AZAN trichrome-stained slides were also analyzed for comparison of collagen evaluation. Sections were stained for phospho-Smad2 (pS2) in order to determine the relationship of TGF-β signaling with stromal organization. RESULTS: A statistically significant relationship was observed between stroma consisting of organised collagen and pathological response to neoadjuvant chemotherapy (Odds Ratio 0.276, 95%CI 0.124-0.614, P = 0.002). This parameter was also related to ER-status (P = 0.003), clinical tumor -status (P = 0.041), nodal status (P = 0.029) and pS2 status (P = 0.025). Correlation between stromal organisation determined on H&E-stained and AZAN-stained tissue sections was high (Pearson's correlation coefficient = 0.806). CONCLUSION: Intratumoral stromal organisation determined using pre-treatment breast cancer biopsies was related to pathological response to chemotherapy. This parameter might play a role in the management of breast cancer for identifying those patients that are likely to benefit from neoadjuvant chemotherapy.
Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Yasushi Kojima; Ahmet Acar; Elinor Ng Eaton; Kieran T Mellody; Christina Scheel; Ittai Ben-Porath; Tamer T Onder; Zhigang C Wang; Andrea L Richardson; Robert A Weinberg; Akira Orimo Journal: Proc Natl Acad Sci U S A Date: 2010-11-01 Impact factor: 11.205
Authors: Esther M de Kruijf; Johanna G H van Nes; Cornelis J H van de Velde; Hein Putter; Vincent T H B M Smit; Gerrit Jan Liefers; Peter J K Kuppen; Rob A E M Tollenaar; Wilma E Mesker Journal: Breast Cancer Res Treat Date: 2010-04-02 Impact factor: 4.872
Authors: A Charehbili; S van de Ven; V T H B M Smit; E Meershoek-Klein Kranenbarg; N A T Hamdy; H Putter; J B Heijns; L J C van Warmerdam; L Kessels; M Dercksen; M J Pepels; E Maartense; H W M van Laarhoven; B Vriens; M N Wasser; A E van Leeuwen-Stok; G J Liefers; C J H van de Velde; J W R Nortier; J R Kroep Journal: Ann Oncol Date: 2014-02-27 Impact factor: 32.976
Authors: Anthony J Trimboli; Carmen Z Cantemir-Stone; Fu Li; Julie A Wallace; Anand Merchant; Nicholas Creasap; John C Thompson; Enrico Caserta; Hui Wang; Jean-Leon Chong; Shan Naidu; Guo Wei; Sudarshana M Sharma; Julie A Stephens; Soledad A Fernandez; Metin N Gurcan; Michael B Weinstein; Sanford H Barsky; Lisa Yee; Thomas J Rosol; Paul C Stromberg; Michael L Robinson; Francois Pepin; Michael Hallett; Morag Park; Michael C Ostrowski; Gustavo Leone Journal: Nature Date: 2009-10-22 Impact factor: 49.962
Authors: Jennifer L Leight; Michele A Wozniak; Sophia Chen; Michelle L Lynch; Christopher S Chen Journal: Mol Biol Cell Date: 2012-01-11 Impact factor: 4.138
Authors: Brent O'Carrigan; Matthew Hf Wong; Melina L Willson; Martin R Stockler; Nick Pavlakis; Annabel Goodwin Journal: Cochrane Database Syst Rev Date: 2017-10-30
Authors: Stéphanie Zunder; Priscilla van der Wilk; Hans Gelderblom; Tim Dekker; Christoph Mancao; Anna Kiialainen; Hein Putter; Rob Tollenaar; Wilma Mesker Journal: Cell Oncol (Dordr) Date: 2019-05-17 Impact factor: 6.730
Authors: Janusz Franco-Barraza; Ralph Francescone; Tiffany Luong; Neelima Shah; Raj Madhani; Gil Cukierman; Essel Dulaimi; Karthik Devarajan; Brian L Egleston; Emmanuelle Nicolas; R Katherine Alpaugh; Ruchi Malik; Robert G Uzzo; John P Hoffman; Erica A Golemis; Edna Cukierman Journal: Elife Date: 2017-01-31 Impact factor: 8.140
Authors: T J A Dekker; A Charehbili; V T H B M Smit; P ten Dijke; E Meershoek-Klein Kranenbarg; C J H van de Velde; J W R Nortier; R A E M Tollenaar; W E Mesker; J R Kroep Journal: Mol Oncol Date: 2015-02-14 Impact factor: 6.603
Authors: Sophie C Hagenaars; Kiki M H Vangangelt; Gabi W Van Pelt; Zsófia Karancsi; Rob A E M Tollenaar; Andrew R Green; Emad A Rakha; Janina Kulka; Wilma E Mesker Journal: Breast Cancer Res Treat Date: 2022-04-16 Impact factor: 4.624
Authors: K M H Vangangelt; G W van Pelt; C C Engels; H Putter; G J Liefers; V T H B M Smit; R A E M Tollenaar; P J K Kuppen; W E Mesker Journal: Breast Cancer Res Treat Date: 2017-12-22 Impact factor: 4.872
Authors: Alexander S Brodsky; Jinjun Xiong; Dongfang Yang; Christoph Schorl; Mary Anne Fenton; Theresa A Graves; William M Sikov; Murray B Resnick; Yihong Wang Journal: BMC Cancer Date: 2016-04-18 Impact factor: 4.430