Tumor Stroma Ratio Colon Cancer

BACKGROUND AND OBJECTIVE: Colon cancer is a fatal disease, and a comprehensive understanding of the tumor microenvironment (TME) could lead to better risk stratification, prognosis prediction, and therapy management. In this paper, we focused on the automatic evaluation of TME in giga-pixel digital histopathology whole-slide images. METHODS: A convolutional neural network is used to recognize nine different content presented in colon cancer whole-slide images. Several implementation details, including the foreground filtering and stain normalization are discussed...

BACKGROUND: The amount of stroma in the primary tumor is an important prognostic parameter. The tumor-stroma ratio (TSR) was previously validated by international research groups as a robust parameter with good interobserver agreement. OBJECTIVE: The Uniform Noting for International Application of the Tumor-Stroma Ratio as an Easy Diagnostic Tool (UNITED) study was developed to bring the TSR to clinical implementation. As part of the study, an e-Learning module was constructed to confirm the reproducibility of scoring the TSR after proper instruction...

Tumor-infiltrating lymphocytes (TILs) are an important histopathologic feature of colorectal cancer that confer prognostic information. Previous clinical and epidemiologic studies have found that the presence and quantification of tumor-infiltrating lymphocytes are significantly associated with disease-specific and overall survival in colorectal cancer. We performed a systematic review and meta-analysis, establishing pooled estimates for survival outcomes based on the presence of TILs in colon cancer. PubMed (Medline), Embase, Cochrane Library, Web of Science, and ClinicalTrials...

The tumor stroma ratio (TSR) is a promising prognostic biomarker in colon cancer, which could provide additional risk stratification for therapy adaption. The objective of our study was the investigation of the prognostic significance of TSR at different tumor sites in a simple semiautomatic approach with the open-source program ImageJ. We investigated 206 pT3 and pT4 adenocarcinomas of no special type. According to our established thresholds, 31 tumors (15%) were classified as low tumor proportion (TP) (≤ 15% TP), 42 tumors (20%) were classified as high TP (≥ 54% TP), and 133 tumors (65%) were classified as medium TP...

BACKGROUND: Colon cancer treatment is dependent on the stage at diagnosis. The current Tumor-Node-Metastasis (TNM) staging for the selection of patients for adjuvant chemotherapy needs additional prognostic and predictive biomarkers. Better decision making for chemotherapy will result in reducing over- and undertreatment. We developed a new, easy-to-apply, practice-changing method to select colon cancer patients for adjuvant chemotherapy: the tumor-stroma ratio (TSR). The TSR distinguishes within stage II-III patients who will likely benefit from adjuvant chemotherapy and those who will not...

PURPOSE: Intra-tumoral stroma has become increasingly important in understanding tumor biology, tumor progression and clinical outcome. The amount itself, quantified as the tumor-stroma ratio (TSR), has proven to be prognostic in stage I-III colon cancer. Also, alterations in stromal organization have been found to provide prognostic and predictive information in certain cancers. Here, we evaluated the predictive value of stromal organization in high-risk stage II and III colon cancer with respect to adjuvant bevacizumab and chemotherapy...

BACKGROUND: The tumor microenvironment has a critical role in regulating cancer cell behavior. Tumors with high stromal content are associated with poor patient outcome. The tumor-stroma ratio (TSR) identifies colorectal cancers (CRC) with poor patient prognosis based on hematoxylin & eosin stained sections. The desmoplastic reaction consists to a great extent of cancer-associated fibroblasts (CAFs) of which different subtypes are known. The aim of this study is to investigate and quantify CAFs present in the tumor stroma of CRC stratified by the TSR to possibly add prognostic significance to the TSR...

Here we present the case of a patient affected by rectal squamous cell carcinoma in which we demonstrated the presence of Human Papillomavirus (HPV) by a variety of techniques. Collectively, the virus was detected not only in the tumor but also in some regional lymph nodes and in non-neoplastic mucosa of the upper tract of large bowel. By contrast, it was not identifiable in its common sites of entry, namely oral and ano-genital region. We also found HPV DNA in the plasma-derived exosome. Next, by in vitro studies, we confirmed the capability of HPV DNA-positive exosomes, isolated from the supernatant of a HPV DNA positive cell line (CaSki), to transfer its DNA to human colon cancer and normal cell lines...

The advanced-stage colon cancer spreads from primary tumor site to distant organs where the colon-unassociated stromal population provides a favorable niche for the growth of tumor cells. The heterocellular interactions between colon cancer cells and colon-unassociated fibroblasts at distant metastatic sites are important, yet these cell-cell interactions for therapeutic strategies for metastatic colon cancer remain underestimated. Recent studies have shown the therapeutic potential of DNA-demethylating epi-drugs 5-azacytidine (AZA) and 5-aza-2'-deoxycytidine (DAC) for the treatment of solid tumors...

The tumor-stroma ratio (TSR) has been reported as a strong, independent prognostic parameter in colon cancer as well as in other epithelial cancer types, and may be implemented to routine pathology diagnostics. The TSR is an easy technique, based on routine hematoxylin and eosin stained histological sections, estimating the amount of stroma present in the primary tumor. It links tumors with high stromal content to poor prognosis. The analysis time is less than 2 min with a low inter-observer variation. Scoring of the TSR has been validated in a number of independent international studies...

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...

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...

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...

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...

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...

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...

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...

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...

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)...

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...