Journal Article
. 2020 Jul; 22(1):76.
doi: 10.1186/s13058-020-01311-9.

A subset of activated fibroblasts is associated with distant relapse in early luminal breast cancer

Claire Bonneau 1 Antoine Eliès 1 Yann Kieffer 1 Brigitte Bourachot 1 Sylvain Ladoire 2 Floriane Pelon 1 Delphine Hequet 3 Jean-Marc Guinebretière 4 Christophe Blanchet 2 Anne Vincent-Salomon 5 Roman Rouzier 3 Fatima Mechta-Grigoriou 6 
Affiliations
  • PMID: 32665033
  •     89 References
  •     4 citations

Abstract

Background: Early luminal breast cancer (BC) represents 70% of newly diagnosed BC cases. Among them, small (under 2 cm) BC without lymph node metastasis (classified as T1N0) have been rarely studied, as their prognosis is generally favorable. Nevertheless, up to 5% of luminal T1N0 BC patients relapse with distant metastases that ultimately prove fatal. The aim of our work was to identify the mechanisms involved in metastatic recurrence in these patients.

Methods: Our study addresses the role that autonomous and non-autonomous tumor cell features play with regard to distant recurrence in early luminal BC patients. We created a cohort of T1N0 luminal BC patients (tumors between 0.5-2 cm without lymph node metastasis) with metastatic recurrence ("cases") and corresponding "controls" (without relapse) matched 1:1 on main prognostic factors: age, grade, and proliferation. We deciphered different characteristics of cancer cells and their tumor micro-environment (TME) by deep analyses using immunohistochemistry. We performed in vitro functional assays and highlighted a new mechanism of cooperation between cancer cells and one particular subset of cancer-associated fibroblasts (CAF).

Results: We found that specific TME features are indicative of relapse in early luminal BC. Indeed, quantitative histological analyses reveal that "cases" are characterized by significant accumulation of a particular CAF subset (CAF-S1) and decrease in CD4+ T lymphocytes, without any other association with immune cells. In multivariate analysis, TME features, in particular CAF-S1 enrichment, remain significantly associated with recurrence, thereby demonstrating their clinical relevance. Finally, by performing functional analyses, we demonstrated that CAF-S1 pro-metastatic activity is mediated by the CDH11/osteoblast cadherin, consistent with bones being a major site of metastases in luminal BC patients.

Conclusions: This study shows that distant recurrence in T1N0 BC is strongly associated with the presence of CAF-S1 fibroblasts. Moreover, we identify CDH11 as a key player in CAF-S1-mediated pro-metastatic activity. This is independent of tumor cells and represents a new prognostic factor. These results could assist clinicians in identifying luminal BC patients with high risk of relapse. Targeted therapies against CAF-S1 using anti-FAP antibody or CDH11-targeting compounds might help in preventing relapse for such patients with activated stroma.

Keywords: CDH11; Cadherin 11; Cancer-associated fibroblasts; Luminal breast cancer; Metastases; Stroma; TILs; Tumor infiltrating lymphocytes; Tumor micro-environment.

Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer.
Ana Costa, Yann Kieffer, +16 authors, Fatima Mechta-Grigoriou.
Cancer Cell, 2018 Feb 20; 33(3). PMID: 29455927
Highly Cited.
Management of small T1a/b breast cancer by tumor subtype.
Tanja Ignatov, Holm Eggemann, +2 authors, Atanas Ignatov.
Breast Cancer Res Treat, 2017 Feb 25; 163(1). PMID: 28233107
The biology and function of fibroblasts in cancer.
Raghu Kalluri.
Nat Rev Cancer, 2016 Aug 24; 16(9). PMID: 27550820
Highly Cited. Review.
The evaluation of tumor-infiltrating lymphocytes (TILs) in breast cancer: recommendations by an International TILs Working Group 2014.
R Salgado, C Denkert, +30 authors, International TILs Working Group 2014.
Ann Oncol, 2014 Sep 13; 26(2). PMID: 25214542    Free PMC article.
Highly Cited.
Impact of Epithelial-Stromal Interactions on Peritumoral Fibroblasts in Ductal Carcinoma in Situ.
Carina Strell, Janna Paulsson, +17 authors, Arne Östman.
J Natl Cancer Inst, 2019 Mar 01; 111(9). PMID: 30816935    Free PMC article.
Comparison of the Performance of 6 Prognostic Signatures for Estrogen Receptor-Positive Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.
Ivana Sestak, Richard Buus, +9 authors, Mitch Dowsett.
JAMA Oncol, 2018 Feb 17; 4(4). PMID: 29450494    Free PMC article.
Highly Cited.
Cadherin-11 is expressed in invasive breast cancer cell lines.
M J Pishvaian, C M Feltes, +3 authors, S W Byers.
Cancer Res, 1999 Feb 24; 59(4). PMID: 10029089
The prognostic role of tumor size in early breast cancer in the era of molecular biology.
Anaid Anna Kasangian, Giorgio Gherardi, +10 authors, Nicla Maria La Verde.
PLoS One, 2017 Dec 07; 12(12). PMID: 29211792    Free PMC article.
The role of reactive oxygen species and metabolism on cancer cells and their microenvironment.
Ana Costa, Alix Scholer-Dahirel, Fatima Mechta-Grigoriou.
Semin Cancer Biol, 2014 Jan 11; 25. PMID: 24406211
Highly Cited. Review.
Inter- and intra-tumoural heterogeneity in cancer-associated fibroblasts of human pancreatic ductal adenocarcinoma.
Cindy Neuzillet, Annemilaï Tijeras-Raballand, +15 authors, Hemant M Kocher.
J Pathol, 2018 Dec 24; 248(1). PMID: 30575030    Free PMC article.
Spatially and functionally distinct subclasses of breast cancer-associated fibroblasts revealed by single cell RNA sequencing.
Michael Bartoschek, Nikolay Oskolkov, +11 authors, Kristian Pietras.
Nat Commun, 2018 Dec 06; 9(1). PMID: 30514914    Free PMC article.
Highly Cited.
IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma.
Giulia Biffi, Tobiloba E Oni, +5 authors, David A Tuveson.
Cancer Discov, 2018 Oct 28; 9(2). PMID: 30366930    Free PMC article.
Highly Cited.
Significance of E-cadherin/beta-catenin complex and cyclin D1 in breast cancer.
Sung-Chul Lim, Mi-Sook Lee.
Oncol Rep, 2002 Aug 09; 9(5). PMID: 12168049
Tailoring therapies--improving the management of early breast cancer: St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2015.
A S Coates, E P Winer, +6 authors, Panel Members.
Ann Oncol, 2015 May 06; 26(8). PMID: 25939896    Free PMC article.
Highly Cited.
Cadherin-11 in synovial lining formation and pathology in arthritis.
David M Lee, Hans P Kiener, +5 authors, Michael B Brenner.
Science, 2007 Jan 27; 315(5814). PMID: 17255475
Highly Cited.
Pro-tumorigenic roles of fibroblast activation protein in cancer: back to the basics.
Ellen Puré, Rachel Blomberg.
Oncogene, 2018 May 04; 37(32). PMID: 29720723    Free PMC article.
Review.
FAP Delineates Heterogeneous and Functionally Divergent Stromal Cells in Immune-Excluded Breast Tumors.
Viviana Cremasco, Jillian L Astarita, +17 authors, Shannon J Turley.
Cancer Immunol Res, 2018 Sep 30; 6(12). PMID: 30266714    Free PMC article.
Highly Cited.
Cadherin-11-mediated interactions with bone marrow stromal/osteoblastic cells support selective colonization of breast cancer cells in bone.
Daisuke Tamura, Toru Hiraga, +2 authors, Toshiyuki Yoneda.
Int J Oncol, 2008 Jun 26; 33(1). PMID: 18575746
Robustness, scalability, and integration of a wound-response gene expression signature in predicting breast cancer survival.
Howard Y Chang, Dimitry S A Nuyten, +10 authors, Marc J van de Vijver.
Proc Natl Acad Sci U S A, 2005 Feb 11; 102(10). PMID: 15701700    Free PMC article.
Highly Cited.
Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti-PD-L1 immunotherapy in pancreatic cancer.
Christine Feig, James O Jones, +12 authors, Douglas T Fearon.
Proc Natl Acad Sci U S A, 2013 Nov 28; 110(50). PMID: 24277834    Free PMC article.
Highly Cited.
Identification of prognostic molecular features in the reactive stroma of human breast and prostate cancer.
Anne Planche, Marina Bacac, +4 authors, Ivan Stamenkovic.
PLoS One, 2011 May 26; 6(5). PMID: 21611158    Free PMC article.
Repeated observation of breast tumor subtypes in independent gene expression data sets.
Therese Sorlie, Robert Tibshirani, +13 authors, David Botstein.
Proc Natl Acad Sci U S A, 2003 Jun 28; 100(14). PMID: 12829800    Free PMC article.
Highly Cited.
Epithelial-mesenchymal transition in breast cancer relates to the basal-like phenotype.
David Sarrió, Socorro María Rodriguez-Pinilla, +3 authors, José Palacios.
Cancer Res, 2008 Feb 19; 68(4). PMID: 18281472
Highly Cited.
An alternatively spliced cadherin-11 enhances human breast cancer cell invasion.
Carolyn M Feltes, Akira Kudo, Orest Blaschuk, Stephen W Byers.
Cancer Res, 2002 Nov 20; 62(22). PMID: 12438268
Tumor infiltrating lymphocytes are prognostic in triple negative breast cancer and predictive for trastuzumab benefit in early breast cancer: results from the FinHER trial.
S Loi, S Michiels, +13 authors, C Sotiriou.
Ann Oncol, 2014 Mar 13; 25(8). PMID: 24608200
Highly Cited.
Loss of E-cadherin promotes metastasis via multiple downstream transcriptional pathways.
Tamer T Onder, Piyush B Gupta, +3 authors, Robert A Weinberg.
Cancer Res, 2008 May 17; 68(10). PMID: 18483246
Highly Cited.
Clinicopathological significance of stromal myofibroblasts in invasive ductal carcinoma of the breast.
Cui Yazhou, Shen Wenlv, Zhang Weidong, Wu Licun.
Tumour Biol, 2005 Jan 04; 25(5-6). PMID: 15627894
Occurence of stromal myofibroblasts in the invasive ductal breast cancer tissue is an unfavourable prognostic factor.
Pawel Surowiak, Dawid Murawa, +8 authors, Hermann Lage.
Anticancer Res, 2007 Aug 19; 27(4C). PMID: 17695471
Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013.
A Goldhirsch, E P Winer, +5 authors, Panel members.
Ann Oncol, 2013 Aug 07; 24(9). PMID: 23917950    Free PMC article.
Highly Cited.
Cadherin-11 in poor prognosis malignancies and rheumatoid arthritis: common target, common therapies.
Shahin Assefnia, Sivanesan Dakshanamurthy, +10 authors, Stephen W Byers.
Oncotarget, 2014 Apr 01; 5(6). PMID: 24681547    Free PMC article.
PAM50 assay and the three-gene model for identifying the major and clinically relevant molecular subtypes of breast cancer.
A Prat, J S Parker, C Fan, C M Perou.
Breast Cancer Res Treat, 2012 Jul 04; 135(1). PMID: 22752290    Free PMC article.
Recommendations for human epidermal growth factor receptor 2 testing in breast cancer: American Society of Clinical Oncology/College of American Pathologists clinical practice guideline update.
Antonio C Wolff, M Elizabeth H Hammond, +19 authors, College of American Pathologists.
J Clin Oncol, 2013 Oct 09; 31(31). PMID: 24101045
Highly Cited.
Prognostic and predictive value of tumor-infiltrating lymphocytes in a phase III randomized adjuvant breast cancer trial in node-positive breast cancer comparing the addition of docetaxel to doxorubicin with doxorubicin-based chemotherapy: BIG 02-98.
Sherene Loi, Nicolas Sirtaine, +13 authors, Christos Sotiriou.
J Clin Oncol, 2013 Jan 24; 31(7). PMID: 23341518
Highly Cited.
Separating favorable from unfavorable prognostic markers in breast cancer: the role of E-cadherin.
R Heimann, F Lan, R McBride, S Hellman.
Cancer Res, 2000 Feb 10; 60(2). PMID: 10667580
Correlation and expression of p53, HER-2, vascular endothelial growth factor (VEGF), and e-cadherin in a high-risk breast-cancer population.
Eugene M Howard, Stephen K Lau, +4 authors, Ruby Kochhar.
Int J Clin Oncol, 2004 Jun 29; 9(3). PMID: 15221598
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer.
Daniel Öhlund, Abram Handly-Santana, +20 authors, David A Tuveson.
J Exp Med, 2017 Feb 25; 214(3). PMID: 28232471    Free PMC article.
Highly Cited.
Neoadjuvant plus adjuvant bevacizumab in early breast cancer (NSABP B-40 [NRG Oncology]): secondary outcomes of a phase 3, randomised controlled trial.
Harry D Bear, Gong Tang, +18 authors, Norman Wolmark.
Lancet Oncol, 2015 Aug 15; 16(9). PMID: 26272770    Free PMC article.
E-cadherin regulates anchorage-independent growth and survival in oral squamous cell carcinoma cells.
S S Kantak, R H Kramer.
J Biol Chem, 1998 Jun 27; 273(27). PMID: 9642258
CD10+GPR77+ Cancer-Associated Fibroblasts Promote Cancer Formation and Chemoresistance by Sustaining Cancer Stemness.
Shicheng Su, Jianing Chen, +15 authors, Erwei Song.
Cell, 2018 Feb 06; 172(4). PMID: 29395328
Highly Cited.
Microvascular proliferation in luminal A and basal-like breast cancer subtypes.
Maria Ryssdal Kraby, Kristi Krüger, +3 authors, Anna M Bofin.
J Clin Pathol, 2015 Jul 16; 68(11). PMID: 26175265
Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials.
Early Breast Cancer Trialists' Collaborative Group (EBCTCG).
Lancet, 2015 Jul 28; 386(10001). PMID: 26211827
Highly Cited.
Extracellular matrix directs phenotypic heterogeneity of activated fibroblasts.
Diana Avery, Priya Govindaraju, +3 authors, Ellen Puré.
Matrix Biol, 2017 Dec 19; 67. PMID: 29248556    Free PMC article.
An immunohistochemically positive E-cadherin status is not always predictive for a good prognosis in human breast cancer.
P Querzoli, D Coradini, +15 authors, S Alberti.
Br J Cancer, 2010 Nov 11; 103(12). PMID: 21063415    Free PMC article.
Collective cell migration in morphogenesis and cancer.
Peter Friedl, Yael Hegerfeldt, Miriam Tusch.
Int J Dev Biol, 2004 Sep 07; 48(5-6). PMID: 15349818
Highly Cited. Review.
Stromal gene expression predicts clinical outcome in breast cancer.
Greg Finak, Nicholas Bertos, +9 authors, Morag Park.
Nat Med, 2008 Apr 29; 14(5). PMID: 18438415
Highly Cited.
Molecular portraits of human breast tumours.
C M Perou, T Sørlie, +15 authors, D Botstein.
Nature, 2000 Aug 30; 406(6797). PMID: 10963602
Highly Cited.
Prognostic value of PAM50 and risk of recurrence score in patients with early-stage breast cancer with long-term follow-up.
Hege O Ohnstad, Elin Borgen, +11 authors, Bjørn Naume.
Breast Cancer Res, 2017 Nov 16; 19(1). PMID: 29137653    Free PMC article.
Cadherin switching: essential for behavioral but not morphological changes during an epithelium-to-mesenchyme transition.
Masato Maeda, Keith R Johnson, Margaret J Wheelock.
J Cell Sci, 2005 Feb 17; 118(Pt 5). PMID: 15713751
Highly Cited.
Role of stromal myofibroblasts in invasive breast cancer: stromal expression of alpha-smooth muscle actin correlates with worse clinical outcome.
Masako Yamashita, Tomoko Ogawa, +5 authors, Taizo Shiraishi.
Breast Cancer, 2010 Oct 28; 19(2). PMID: 20978953
New insights into the metastatic behavior after breast cancer surgery, according to well-established clinicopathological variables and molecular subtypes.
Oreste Claudio Buonomo, Emanuele Caredda, +6 authors, Paolo Orsaria.
PLoS One, 2017 Sep 19; 12(9). PMID: 28922402    Free PMC article.
Patterns of breast cancer relapse in accordance to biological subtype.
Atanas Ignatov, Holm Eggemann, Elke Burger, Tanja Ignatov.
J Cancer Res Clin Oncol, 2018 Apr 21; 144(7). PMID: 29675790
Oxidative stress promotes myofibroblast differentiation and tumour spreading.
Aurore Toullec, Damien Gerald, +14 authors, Fatima Mechta-Grigoriou.
EMBO Mol Med, 2010 Jun 11; 2(6). PMID: 20535745    Free PMC article.
Highly Cited.
Exploration of tumour-infiltrating lymphocytes as a predictive biomarker for adjuvant endocrine therapy in early breast cancer.
Erik J Blok, Charla C Engels, +11 authors, Peter J K Kuppen.
Breast Cancer Res Treat, 2018 May 17; 171(1). PMID: 29766362
Molecular cloning and characterization of OB-cadherin, a new member of cadherin family expressed in osteoblasts.
M Okazaki, S Takeshita, +4 authors, E Amann.
J Biol Chem, 1994 Apr 22; 269(16). PMID: 8163513
Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast.
C E Gillett, D W Miles, +5 authors, A M Hanby.
J Pathol, 2001 Mar 29; 193(4). PMID: 11276001
Expression and function of the splice variant of the human cadherin-11 gene in subordination to intact cadherin-11.
J Kawaguchi, S Takeshita, +3 authors, A Kudo.
J Bone Miner Res, 1999 May 13; 14(5). PMID: 10320525
miR200-regulated CXCL12β promotes fibroblast heterogeneity and immunosuppression in ovarian cancers.
Anne-Marie Givel, Yann Kieffer, +10 authors, Fatima Mechta-Grigoriou.
Nat Commun, 2018 Mar 15; 9(1). PMID: 29535360    Free PMC article.
Highly Cited.
Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual.
Armando E Giuliano, James L Connolly, +6 authors, Gabriel N Hortobagyi.
CA Cancer J Clin, 2017 Mar 16; 67(4). PMID: 28294295
Highly Cited.
Hallmarks of cancer: interactions with the tumor stroma.
Kristian Pietras, Arne Ostman.
Exp Cell Res, 2010 Mar 10; 316(8). PMID: 20211171
Highly Cited. Review.
Expression of e-cadherin in high-risk breast cancer.
Eugene M Howard, Stephen K Lau, +3 authors, Ruby Kochhar.
J Cancer Res Clin Oncol, 2004 Oct 02; 131(1). PMID: 15459769
Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome.
A Bergamaschi, E Tagliabue, +10 authors, A-L Børresen-Dale.
J Pathol, 2007 Nov 30; 214(3). PMID: 18044827
Highly Cited.
The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer.
S Muenst, S D Soysal, +3 authors, W E Gillanders.
Breast Cancer Res Treat, 2013 Jun 13; 139(3). PMID: 23756627    Free PMC article.
Highly Cited.
Development and verification of the PAM50-based Prosigna breast cancer gene signature assay.
Brett Wallden, James Storhoff, +16 authors, Joel S Parker.
BMC Med Genomics, 2015 Aug 25; 8. PMID: 26297356    Free PMC article.
Highly Cited.
Characterization and clinical evaluation of CD10+ stroma cells in the breast cancer microenvironment.
Christine Desmedt, Samira Majjaj, +18 authors, Christos Sotiriou.
Clin Cancer Res, 2012 Jan 12; 18(4). PMID: 22235100    Free PMC article.
Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors.
Huipeng Li, Elise T Courtois, +14 authors, Shyam Prabhakar.
Nat Genet, 2017 Mar 21; 49(5). PMID: 28319088
Highly Cited.
E-cadherin as a prognostic indicator in primary breast cancer.
C Parker, R S Rampaul, +5 authors, J F Robertson.
Br J Cancer, 2001 Dec 19; 85(12). PMID: 11747340    Free PMC article.
Prognostic value of reduced E-cadherin expression in breast cancer: a meta-analysis.
Zhan Li, Songcheng Yin, +2 authors, Bo Chen.
Oncotarget, 2017 Feb 02; 8(10). PMID: 28147315    Free PMC article.
Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases.
Petros P Sfikakis, Nikolaos I Vlachogiannis, Panagiotis F Christopoulos.
Clin Immunol, 2017 Jan 25; 176. PMID: 28115292
Review.
The E-cadherin/catenin complex: an important gatekeeper in breast cancer tumorigenesis and malignant progression.
G Berx, F Van Roy.
Breast Cancer Res, 2001 Oct 13; 3(5). PMID: 11597316    Free PMC article.
Highly Cited. Review.
Gene expression profiling of the tumor microenvironment during breast cancer progression.
Xiao-Jun Ma, Sonika Dahiya, +2 authors, Dennis C Sgroi.
Breast Cancer Res, 2009 Feb 04; 11(1). PMID: 19187537    Free PMC article.
Highly Cited.
A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer.
Torsten O Nielsen, Joel S Parker, +12 authors, Matthew J Ellis.
Clin Cancer Res, 2010 Sep 15; 16(21). PMID: 20837693    Free PMC article.
Highly Cited.
Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications.
T Sørlie, C M Perou, +14 authors, A L Børresen-Dale.
Proc Natl Acad Sci U S A, 2001 Sep 13; 98(19). PMID: 11553815    Free PMC article.
Highly Cited.
Tumor-infiltrating CD8+ lymphocytes predict clinical outcome in breast cancer.
Sahar M A Mahmoud, Emma Claire Paish, +5 authors, Andrew R Green.
J Clin Oncol, 2011 Apr 13; 29(15). PMID: 21483002
Highly Cited.
E-cadherin is required for metastasis in multiple models of breast cancer.
Veena Padmanaban, Ilona Krol, +4 authors, Andrew J Ewald.
Nature, 2019 Sep 06; 573(7774). PMID: 31485072    Free PMC article.
Highly Cited.
Expression of S100A4, E-cadherin, alpha- and beta-catenin in breast cancer biopsies.
K B Pedersen, J M Nesland, Ø Fodstad, G M Maelandsmo.
Br J Cancer, 2002 Nov 20; 87(11). PMID: 12439718    Free PMC article.
Prognosis and management of patients with node-negative invasive breast carcinoma that is 1 cm or smaller in size (stage 1; T1a,bN0M0): a review of the literature.
Emer O Hanrahan, Vicente Valero, Ana M Gonzalez-Angulo, Gabriel N Hortobagyi.
J Clin Oncol, 2006 May 02; 24(13). PMID: 16648513
Review.
Altered expression of E-cadherin in breast cancer. patterns, mechanisms and clinical significance.
K S Asgeirsson, J G Jónasson, +4 authors, H M Ogmundsdóttir.
Eur J Cancer, 2000 Jun 16; 36(9). PMID: 10854942
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
Freddie Bray, Jacques Ferlay, +3 authors, Ahmedin Jemal.
CA Cancer J Clin, 2018 Sep 13; 68(6). PMID: 30207593
Highly Cited.
Prognostic significance in breast cancer of a gene signature capturing stromal PDGF signaling.
Oliver Frings, Martin Augsten, +8 authors, Erik L L Sonnhammer.
Am J Pathol, 2013 Apr 16; 182(6). PMID: 23583284
E-cadherin immunohistochemical expression as a prognostic factor in infiltrating ductal carcinoma of the breast: a systematic review and meta-analysis.
Bonnie E Gould Rothberg, Michael B Bracken.
Breast Cancer Res Treat, 2006 Jun 23; 100(2). PMID: 16791476
Systematic Review.
Immune recurrence score using 7 immunoregulatory protein expressions can predict recurrence in stage I-III breast cancer patients.
Dae-Won Lee, Han Suk Ryu, +14 authors, Seock-Ah Im.
Br J Cancer, 2019 Jul 12; 121(3). PMID: 31292534    Free PMC article.
E-cadherin expression in invasive non-lobular carcinoma of the breast and its prognostic significance.
E A Rakha, D Abd El Rehim, +2 authors, I O Ellis.
Histopathology, 2005 May 25; 46(6). PMID: 15910600
Accelerated instability testing reveals quantitative mass spectrometry overcomes specimen storage limitations associated with PD-L1 immunohistochemistry.
Alexander Haragan, Daniel C Liebler, +8 authors, Aaron M Gruver.
Lab Invest, 2020 Jan 04; 100(6). PMID: 31896815    Free PMC article.
Next generation sequencing-based expression profiling identifies signatures from benign stromal proliferations that define stromal components of breast cancer.
Xiangqian Guo, Shirley X Zhu, +2 authors, Robert B West.
Breast Cancer Res, 2013 Dec 18; 15(6). PMID: 24342436    Free PMC article.
E-cadherin deregulation in breast cancer.
Giovanni Corso, Joana Figueiredo, +12 authors, Sara Gandini.
J Cell Mol Med, 2020 Apr 18; 24(11). PMID: 32301282    Free PMC article.
Review.
PAM50 Risk of Recurrence Score Predicts 10-Year Distant Recurrence in a Comprehensive Danish Cohort of Postmenopausal Women Allocated to 5 Years of Endocrine Therapy for Hormone Receptor-Positive Early Breast Cancer.
Anne-Vibeke Lænkholm, Maj-Britt Jensen, +12 authors, Bent Ejlertsen.
J Clin Oncol, 2018 Jan 26; 36(8). PMID: 29369732
Cancer-associated fibroblast heterogeneity in axillary lymph nodes drives metastases in breast cancer through complementary mechanisms.
Floriane Pelon, Brigitte Bourachot, +15 authors, Fatima Mechta-Grigoriou.
Nat Commun, 2020 Jan 23; 11(1). PMID: 31964880    Free PMC article.
Cell adhesion and drug resistance in cancer.
B St Croix, R S Kerbel.
Curr Opin Oncol, 1997 Nov 25; 9(6). PMID: 9370076
Review.
Overall survival and cause-specific mortality of patients with stage T1a,bN0M0 breast carcinoma.
Emer O Hanrahan, Ana M Gonzalez-Angulo, +4 authors, Vicente Valero.
J Clin Oncol, 2007 Nov 01; 25(31). PMID: 17971593
Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective.
Géraldine Gentric, Fatima Mechta-Grigoriou.
Cancers (Basel), 2021 Jan 28; 13(3). PMID: 33499022    Free PMC article.
Review.
The Tumor Microenvironment in Liver Metastases from Colorectal Carcinoma in the Context of the Histologic Growth Patterns.
Gemma Garcia-Vicién, Artur Mezheyeuski, +2 authors, David G Molleví.
Int J Mol Sci, 2021 Feb 07; 22(4). PMID: 33546502    Free PMC article.
Review.
The Role of Tumor Microenvironment in Cancer Metastasis: Molecular Mechanisms and Therapeutic Opportunities.
Christiana M Neophytou, Myrofora Panagi, Triantafyllos Stylianopoulos, Panagiotis Papageorgis.
Cancers (Basel), 2021 May 01; 13(9). PMID: 33922795    Free PMC article.
Review.
Signaling pathways in cancer-associated fibroblasts and targeted therapy for cancer.
Fanglong Wu, Jin Yang, +5 authors, Hongmei Zhou.
Signal Transduct Target Ther, 2021 Jun 11; 6(1). PMID: 34108441    Free PMC article.
Review.