Stromal Responses among Carcinomas−−Letter Tiziana Triulzi, Rosaria Orlandi and Elda Tagliabue Clin Cancer Res 2014;20:1396.
Updated version
Cited Articles
E-mail alerts Reprints and Subscriptions Permissions
Access the most recent version of this article at: http://clincancerres.aacrjournals.org/content/20/5/1396
This article cites by 7 articles, 2 of which you can access for free at: http://clincancerres.aacrjournals.org/content/20/5/1396.full.html#ref-list-1
Sign up to receive free email-alerts related to this article or journal. To order reprints of this article or to subscribe to the journal, contact the AACR Publications Department at
[email protected]. To request permission to re-use all or part of this article, contact the AACR Publications Department at
[email protected].
Downloaded from clincancerres.aacrjournals.org on March 2, 2014. © 2014 American Association for Cancer Research.
Clinical Cancer Research
Letter to the Editor
Stromal Responses among Carcinomas—Letter Tiziana Triulzi, Rosaria Orlandi, and Elda Tagliabue
Chen and colleagues (1) described a fibroblastic signature desmoid-type fibromatosis (DTF) as a common feature in different types of carcinomas (prostate, ovarian, colon, and lung). These data are very interesting and relevant from a biologic point of view because they suggest that for a subgroup of patients, this feature represents a common stromal response to cancer in different organs, but with opposite prognostic power according to tumor type. Indeed, although DTF predicts worse outcome in ovarian and colon carcinomas, the same authors found association of this signature with good outcome in breast carcinomas (2). However, the authors’ conclusion is not fully warranted on the basis of the findings presented. Stromal signatures discovered in breast carcinomas, including stromal metagene (3), SDPP (4), and our own ECM3 (5), have higher or even opposite prognostic/predictive power when combined with existing outcome predictors [i.e, estrogen receptor (ER), HER2, and grade]. We found that ECM3, characterized by upmodulation of DTFassociated genes (6), has an independent negative prog-
Authors' Affiliation: Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy Corresponding Author: Elda Tagliabue, Molecular Targeting Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, via Amadeo 42, 20133 Milan, Italy. Phone: 39-02-2390-3013; Fax: 39-02-2390-2692; E-mail:
[email protected] doi: 10.1158/1078-0432.CCR-13-3005 Ó2014 American Association for Cancer Research.
nostic role only in chemotherapy-untreated grade 3 breast carcinomas, whereas it is slightly associated with better outcome in differentiated tumors (5). Thus, even in absence of a significant association between DTF and specific tumor characteristics, this stromal signature may influence disease progression differently in the same tumor type according to characteristics of the neoplastic cells. Although the disparity in prognostic results according to tumor type is attributable to variations in carcinoma stage in the publicly available datasets, as postulated by the authors themselves, it also raises the possibility that DTF, conserved across different types of carcinomas, is associated with the same responses in tumors of different origin but with similar stage characteristics. In addition, because chemotherapy significantly affects the features of the tumor microenvironment (7), analysis of the clinical significance of DTF should be performed separately in tumors of treated and untreated patients. Accordingly, stromal metagene, which is strongly correlated with DTF (2), was found predictive in ER-negative chemotherapy-treated carcinomas but not prognostic in untreated ER-negative breast carcinomas (3). In summary, we suggest that conclusions about a clinical role for DTF in different tumor types await further analyses that consider the interaction of tumor stromal characteristics with neoplastic cell molecular traits and with the therapeutic treatment of the patient. Disclosure of Potential Conflicts of Interest No potential conflicts of interest were disclosed. Received October 31, 2013; accepted November 15, 2013; published online March 3, 2014.
References 1. Chen JL, Espinosa I, Lin AY, Liao OY, van de RM, West RB. Stromal responses among common carcinomas correlated with clinicopathologic features. Clin Cancer Res 2013;19:5127–35. 2. West RB, Nuyten DS, Subramanian S, Nielsen TO, Corless CL, Rubin BP, et al. Determination of stromal signatures in breast carcinoma. PLoS Biol 2005;3:e187. 3. Farmer P, Bonnefoi H, Anderle P, Cameron D, Wirapati P, Becette V, et al. A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer. Nat Med 2009;15:68–74. 4. Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, Zhao H, et al. Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 2008;14:518–27.
1396
5. Triulzi T, Casalini P, Sandri M, Ratti F, Carcangiu ML, Colombo MP, et al. Neoplastic and stromal cells contribute to an extracellular matrix gene expression profile defining a breast cancer subtype likely to progress. PLoS ONE 2013;8:e56761. 6. Bergamaschi A, Tagliabue E, Sorlie T, Naume B, Triulzi T, Orlandi R, et al. Extracellular matrix signature identifies breast cancer subgroups with different clinical outcome. J Pathol 2008;214: 357–67. S, Castiglioni F, Bertola L, Cantu M, Bongarzone I, et al. 7. Pupa SM, Giuffre Regulation of breast cancer response to chemotherapy by fibulin-1. Cancer Res 2007;67:4271–7.
Clin Cancer Res; 20(5) March 1, 2014
Downloaded from clincancerres.aacrjournals.org on March 2, 2014. © 2014 American Association for Cancer Research.