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Tumor Stroma Ratio Colon Cancer

Anouck Huijbers, Gabi W van Pelt, Rachel S Kerr, Elaine C Johnstone, Rob A E M Tollenaar, David J Kerr, Wilma E Mesker
INTRODUCTION: Patients with a high stroma percentage within the primary tumor have a poor prognosis. In this study, we investigate whether anti-angiogenic therapy might improve survival of patients with a stroma-high profile with potentially increased angiogenesis. MATERIALS AND METHODS: Tissue samples of the primary tumor of 965 colon cancer patients participating in the QUASAR2 trial were analyzed for tumor-stroma ratio (TSR). Stroma-high (>50%) and stroma-low (≤50%) groups were evaluated with respect to survival...
February 15, 2018: Journal of Surgical Oncology
Guanghua Liu, Shi Feng, Lin Jia, Chunying Wang, Yan Fu, Yongzhang Luo
As a rate-limiting step in metastasis, metastatic colonization requires survival signals from supportive stroma. However, the mechanisms driving this process are incompletely understood. Here, we showed that the proliferation of B16F10 cells was promoted when cocultured with lung fibroblasts. Meanwhile, co-injection of B16F10 tumor cells with mouse lung fibroblasts significantly increased lung metastasis. Based on GEO database, we identified stearoyl-CoA desaturase 1 (SCD1) as a novel factor promoting metastatic colonization...
March 2018: Oncogene
Torben Frøstrup Hansen, Sanne Kjær-Frifeldt, Jan Lindebjerg, Søren Rafael Rafaelsen, Lars Henrik Jensen, Anders Jakobsen, Flemming Brandt Sørensen
BACKGROUND: Neoadjuvant chemotherapy represents a new treatment approach to locally advanced colon cancer. The aim of this study was to analyze the ability of tumor-stroma ratio (TSR) to predict disease recurrence in patients with locally advanced colon cancer treated with neoadjuvant chemotherapy. MATERIAL AND METHODS: This study included 65 patients with colon cancer treated with neoadjuvant chemotherapy in a phase II trial. All patients were planned for three cycles of capecitabine and oxaliplatin before surgery...
October 5, 2017: Acta Oncologica
P Miller, K M Kidwell, D Thomas, M Sabel, J M Rae, D F Hayes, B I Hudson, D El-Ashry, M E Lippman
PURPOSE: Elevated S100A8 expression has been observed in cancers of the bladder, esophagus, colon, ovary, and breast. S100A8 is expressed by breast cancer cells as well as by infiltrating immune and myeloid cells. Here we investigate the association of elevated S100A8 protein expression in breast cancer cells and in breast tumor stroma with survival outcomes in a cohort of breast cancer patients. PATIENTS AND METHODS: Tissue microarrays (TMA) were constructed from breast cancer specimens from 417 patients with stage I-III breast cancer treated at the University of Michigan Comprehensive Cancer Center between 2004 and 2006...
July 17, 2017: Breast Cancer Research and Treatment
Elisa Gilardoni, Davide Paolo Bernasconi, Silvia Poli, Mattia Garancini, Margherita Luperto, Nicola Zucchini, Giorgio Bovo, Mauro Totis, Alvaro Bugatti, Luca Gianotti
BACKGROUND: Although several meta-analyses showed the positive effects of follow-up on the prognosis of colon cancer (CC), international guidelines are not in accordance on appropriate tests and their time frequency to optimize surveillance. Furthermore, stratified strategies based upon risk grading have not been implemented. This approach may be useful to rationalize resources. METHODS: From 2006, all patients operated for an early stage CC (I, IIA, IIB) according to the 7th edition of the AJCC-2010 classification entered in a prospective surveillance program in accordance to our local guidelines...
2015: World Journal of Surgical Oncology
Dorina Rama-Esendagli, Gunes Esendagli, Guldal Yilmaz, Dicle Guc
Interactions with stromal components influence the growth, survival, spread, and colonization capacities of tumor cells. Fibroblasts and macrophages which are responsible for the stroma production and maintenance are of the basic elements found in tumor microenvironment. Cellular density and ratio of stromal cells to tumor cells can also have modulatory effects in cancer. Here, the contribution of fibroblast and/or macrophage cells on the malignant behavior of breast cancer cells was modeled in co-culture systems...
May 2014: Molecular Biology Reports
J H Park, C H Richards, D C McMillan, P G Horgan, C S D Roxburgh
BACKGROUND: Tumour stroma percentage (TSP) has previously been reported to predict survival in patients with colorectal cancer (CRC); however, whether this is independent of other aspects of the tumour microenvironment is unknown. In the present study, the relationship between TSP, the tumour microenvironment and survival was examined in patients undergoing elective, curative CRC resection. PATIENTS AND METHODS: Patients undergoing resection at a single centre (1997-2008) were identified from a prospective database...
March 2014: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Maria L Wikberg, Sofia Edin, Ida V Lundberg, Bethany Van Guelpen, Anna M Dahlin, Jörgen Rutegård, Roger Stenling, Ake Oberg, Richard Palmqvist
An active stroma is important for cancer cell invasion and metastasis. We investigated the expression of fibroblast activation protein (FAP) in relation to patient prognosis in colorectal cancer. Colorectal cancer specimens from 449 patients were immunohistochemically stained with a FAP antibody and evaluated in the tumor center and tumor front using a semiquantitative four-level scale. FAP was expressed by fibroblasts in 85-90 % of the tumors examined. High versus no/low expression in the tumor center was associated with poor prognosis (multivariate hazard ratio, HR = 1...
April 2013: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Harry H Yoon, Jared M Orrock, Nathan R Foster, Daniel J Sargent, Thomas C Smyrk, Frank A Sinicrope
BACKGROUND: T-lymphocyte infiltration into colon carcinomas can influence clinical outcome, and interactions among T cell subsets may be more informative than either subset alone. Our objective was to examine the prognostic impact of tumor-infiltrating FoxP3(+) regulatory T cells (Tregs) in relation to cytotoxic CD8(+) T lymphocytes in patients with colon carcinomas characterized by DNA mismatch repair (MMR) status who participated in adjuvant chemotherapy trials. METHODS: FoxP3(+) and CD8(+) densities in tumor epithelial and stromal compartments were analyzed by immunohistochemistry and quantified in resected, stage II and III colonic carcinomas (N = 216)...
2012: PloS One
A Huijbers, R A E M Tollenaar, G W v Pelt, E C M Zeestraten, S Dutton, C C McConkey, E Domingo, V T H B M Smit, R Midgley, B F Warren, E C Johnstone, D J Kerr, W E Mesker
BACKGROUND: The intra-tumor stroma percentage in colon cancer (CC) patients has previously been reported by our group as a strong independent prognostic parameter. Patients with a high stroma percentage within the primary tumor have a poor prognosis. PATIENTS AND METHODS: Tissue samples from the most invasive part of the primary tumor of 710 patients (52% Stage II, 48% Stage III) participating in the VICTOR trial were analyzed for their tumor-stroma percentage. Stroma-high (>50%) and stroma-low (≤50%) groups were evaluated with respect to survival times...
January 2013: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Anna M Dahlin, Maria L Henriksson, Bethany Van Guelpen, Roger Stenling, Ake Oberg, Jörgen Rutegård, Richard Palmqvist
The aim of this study was to relate the density of tumor infiltrating T cells to cancer-specific survival in colorectal cancer, taking into consideration the CpG island methylator phenotype (CIMP) and microsatellite instability (MSI) screening status. The T-cell marker CD3 was stained by immunohistochemistry in 484 archival tumor tissue samples. T-cell density was semiquantitatively estimated and scored 1-4 in the tumor front and center (T cells in stroma), and intraepithelially (T cells infiltrating tumor cell nests)...
May 2011: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Mary P Bronner, Marek Skacel, David A Crispin, Peter D Hoff, Mary J Emond, Lisa A Lai, Raymond R Tubbs, Jacintha N O'Sullivan, Peter S Rabinovitch, Teresa A Brentnall
Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At present, identification of this subset is markedly limited and necessitates lifelong colonoscopic surveillance for the entire ulcerative colitis population. Better risk markers are needed to focus surveillance onto the patients who are most likely to benefit. Using array-based comparative genomic hybridization, we analyzed single, non-dysplastic biopsies from three patient groups: ulcerative colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance of 18 cm from the analyzed site; ulcerative colitis non-progressors (n=8) without dysplasia during long-term surveillance; and non-ulcerative colitis normal controls (n=2)...
December 2010: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Wilma E Mesker, Gerrit-Jan Liefers, Jan M C Junggeburt, Gabi W van Pelt, Paola Alberici, Peter J K Kuppen, Noel F Miranda, Karin A M van Leeuwen, Hans Morreau, Karoly Szuhai, Rob A E M Tollenaar, Hans J Tanke
BACKGROUND: For stage I-II colon cancer a significant number (5-25%) of patients has recurrent disease within 5 years. There is need to identify these high-risk patients as they might benefit from additional treatment. Stroma-tissue surrounding the cancer cells plays an important role in the tumor behavior. The proportion of intra-tumor stroma was evaluated for the identification of high-risk patients. In addition, protein expression of markers involved in pathways related to stroma production and epithelial-to-mesenchymal transition (EMT) was analyzed: beta-catenin, TGF-beta-R2 and SMAD4...
2009: Cellular Oncology: the Official Journal of the International Society for Cellular Oncology
Yansong Bian, Thomas J Knobloch, Maureen Sadim, Virginia Kaklamani, Adekunle Raji, Guang-Yu Yang, Christopher M Weghorst, Boris Pasche
TGFBR1*6A is a common hypomorphic variant of the type I transforming growth factor (TGF)-beta receptor (TGFBR1), which transduces TGF-beta growth inhibitory signals less effectively than TGFBR1. Recent studies suggest that TGFBR1*6A confers a selective growth advantage to both normal appearing and cancerous epithelial cells in the presence of TGF-beta. We have previously shown that TGFBR1*6A is somatically acquired in head and neck and colon cancer (10). Using microdissected tissues, we show that TGFBR1*6A is somatically acquired by stromal and epithelial cells adjacent to colorectal and head and neck tumors...
December 15, 2007: Human Molecular Genetics
Kumari L Andarawewa, Elena R Motrescu, Marie-Pierre Chenard, Anne Gansmuller, Isabelle Stoll, Catherine Tomasetto, Marie-Christine Rio
The initial invasive processes during cancer development remain largely unknown. Stromelysin-3/matrix metalloproteinase 11 (ST3/MMP11) is associated with tumor invasion and poor prognosis. We present novel evidence that adipocytes present at human breast tumor invasive front are induced by cancer cells to express ST3. Using mouse syngeneic model, light and electron microscopy showed that in ST3-deficient mice but not in wild-type mice, forced cancer cell-adipocyte interaction/crosstalk results in adipocyte membrane alteration, allowing cancer cell fat infiltration and death...
December 1, 2005: Cancer Research
Jingfang Gao, Gunnar Arbman, Ann Rearden, Xiao-Feng Sun
Particularly interesting new cysteine-histidine-rich protein (PINCH), a LIM domain adapter protein that functions in the integrin and growth factor signal transduction pathway, is upregulated in stroma associated with many common cancers. The finding suggested that PINCH may be involved in promoting tumor-stromal interactions that support tumor progression, and, if so, tumors with abundant PINCH stromal staining may have a worse prognosis. To test this hypothesis, 174 primary colorectal adenocarcinomas with 39 distant normal mucosa samples and 26 metastases in the lymph nodes were studied by immunohistochemistry, and 7 additional colon tumors were studied by Western blot analysis and immunofluorescence...
November 2004: Neoplasia: An International Journal for Oncology Research
Alok A Khorana, Charlotte K Ryan, Christopher Cox, Shirley Eberly, Deepak M Sahasrabudhe
BACKGROUND: The elucidation of new therapeutic targets of prognostic significance in colon carcinoma is necessary to improve outcomes. In the current study, the authors examined the expression of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) in primary colon carcinoma cases and VEGF in tumor-associated macrophages (TAM)/stroma, and their correlation with survival. METHODS: The authors identified 131 consecutive American Joint Committee on Cancer Stage II and Stage III colon carcinoma patients seen at the University of Rochester between 1990-1995...
February 15, 2003: Cancer
Jennifer A Tuxhorn, Stephanie J McAlhany, Truong D Dang, Gustavo E Ayala, David R Rowley
Reactive stroma has been reported in many cancers, including breast, colon,and prostate. Although changes in stromal cell phenotype and extracellular matrix have been reported, specific mechanisms of how reactive stroma affects tumor progression are not understood. To address the role of stromal cells in differential regulation of tumor incidence, growth rate, and angiogenesis, LNCaP xenograft tumors were constructed in nude mice with five different human prostate stromal cell lines as well as GeneSwitch-3T3 cells engineered to express lacZ under mifepristone regulation...
June 1, 2002: Cancer Research
T Etoh, K Shibuta, G F Barnard, S Kitano, M Mori
Tumor angiogenesis is essential for tumor growth and tumor metastasis, and it depends on angiogenic factors produced by tumor cells and/or infiltrating cells in tumor tissue. In this study, we evaluated the clinical significance of the expression of angiogenin, which is a potent angiogenic protein, and the relationship between its mRNA expression and focal macrophage infiltration in colorectal cancer. Furthermore, we investigated the induction of angiogenin mRNA expression by proinflammatory cytokines mainly produced by inflammatory cells in tumor tissues...
September 2000: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
S Welt, C R Divgi, A M Scott, P Garin-Chesa, R D Finn, M Graham, E A Carswell, A Cohen, S M Larson, L J Old
PURPOSE: To define the toxicity, imaging, and biodistribution characteristics of iodine 131-labeled monoclonal antibody F19 (131I-mAbF19). MAbF19 recognizes the fibroblast activation protein (FAP), a cell-surface glycoprotein not present in most normal tissues, but abundantly expressed by reactive stromal fibroblasts of epithelial cancers, including more than 95% of primary and metastatic colorectal carcinomas. PATIENTS AND METHODS: 131I-mAbF19 was administered intravenously to 17 patients with hepatic metastases from colorectal carcinoma who were scheduled for resection of localized metastases or insertion of hepatic artery catheter for regional chemotherapy...
June 1994: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
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