Abstract 811: Stroma production within the primary tumor correlates with poor survival for stage I-II colon cancer patients
Authors: Mesker Wilma E. , Johnstone Elaine C. , van Pelt Gabi W. , Midgley Rachel , Liefers Gerrit- Jan , Smit Vincent T.H.B.M. , Kerr David J. , Tollenaar Rob A. 
Published: February 2011

Abstract
Background Recent models on metastatic invasion focus on the tumor-“host” interface, in particular the role of the stromal tissue. The stromal compartments are thought to play a major role in the process of wound healing, but there is also strong emphasis that CAF's (cancer-associated fibroblasts) are important promotors for tumor growth and progression. Assuming these models are correct we hypothesized that changes in the proportion of stroma in the primary tumor could reflect progression. We therefore investigated if the amount of intra-tumor stroma could be used as a candidate marker to identify which patients should be selected for adjuvant therapy and furthermore if treatment with a COX-2 inhibitor might improve patient outcome in those patients with high percentage of stroma (with or without chemotherapy)
Methods We have investigated the proportion of intra-tumor stroma on heamatoxylin-eosin (H&E) stained histological sections and distinguished between patients with a high amount of stroma (stroma-high) and patients with lower levels of stroma (stroma-low).
We have analyzed 135 stage I-II colon cancer patients for the proportion of tumor related stroma and for TGFβ-R2, SMAD4 and β-catenin, markers involved in pathways related to stromal production and epithelial-to-mesenchymal transition (EMT).
A series of 596 patients treated either with placebo or COX-2 inhibitor was also analyzed for proportion of stroma (VICTOR-trial).
Results
Of 135 analyzed patients 35 (25.7%) patients were stroma-high and 101 (74.3%) stroma-low. Significant differences in survival were observed between the two groups, with stroma-high patients showing poor survival (OS p&lt;0.0001, HZ 2.59; DFS p=0.0002, HZ 2.31).
A high-risk group (n=14) was identified with stroma-high and SMAD4 loss (OS p=0.008, HZ 7.98, CI 4.12-15.44, DFS p=0.005, HZ 6.57, CI 3.43-12.56); 12 of 14 (85.7%) patients died within 3 years. In a logistic-regression analysis a high proportion of stroma and SMAD4 loss were strongly related (HZ 5.42, CI 2.13-13.82, p&lt;0.001).
Results of the COX-2 inhibitor study are currently under evaluation but will be presented at the conference.
Conclusions: Conventional haematoxylin-eosin stained tumor slides contain more prognostic information than previously fathomed. This can be utilized by assessing the tumor-stroma ratio. The combination of analyzing the tumor-stroma ratio and staining for SMAD4 results in an independent parameter for confident prediction of clinical outcome. The inclusion of this parameter into standard pathological reports should be considered, in addition to the TNM classification.
Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 811.