Stroma-normalised vessel density predicts benefit from adjuvant fluorouracil-based chemotherapy in patients with stage II/III colon cancer.

Background: Identification of biomarkers associated with benefit of adjuvant chemotherapy in stage II/III colon cancer is an important task.

Methods: Vessel density (VD) and tumour stroma were analysed in a randomised-trial-derived discovery cohort (n = 312) and in a stage II/III group of a population-based validation cohort (n = 85). VD was scored separately in the tumour centre, invasive margin and peritumoral stroma compartments and quantitated as VD/total analysed tissue area or VD/stroma area.

Tumor Budding Mismatch Repair Status in Colorectal Cancer - An Exploratory Analysis.

Background: Tumor budding and a proficient mismatch repair (pMMR) status are considered adverse prognostic factors in colorectal cancer (CRC). The aim of this pilot study was to assess tumor budding in primary CRC with pMMR versus that with deficient mismatch repair (dMMR).

Materials And Methods: Tumor budding was retrospectively examined in the tumor from 134 patients with stage II and stage III CRC with known MMR status.

Multi-parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour-type-specific stroma phenotypes and a novel vascular biomarker.

A novel set of integrated procedures for quantification of fibroblast-rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well-annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression.

Image analysis-derived metrics of histomorphological complexity predicts prognosis and treatment response in stage II-III colon cancer.

The complexity of tumor histomorphology reflects underlying tumor biology impacting on natural course and response to treatment. This study presents a method of computer-aided analysis of tissue sections, relying on multifractal (MF) analyses, of cytokeratin-stained tumor sections which quantitatively evaluates of the morphological complexity of the tumor-stroma interface. This approach was applied to colon cancer collection, from an adjuvant treatment randomized study.

Epidemiology of cutaneous melanoma in Sweden-Stage-specific survival and rate of recurrence.

Cutaneous malignant melanoma (CMM) incidence is increasing globally, making a thorough understanding of the disease and its outcomes essential for optimizing care even more urgent. In this population-based, retrospective study, we investigated stage-specific survival and recurrence/progression rates of CMM among patients diagnosed in Stockholm County Council during 2005-2012, before the wide introduction of targeted therapy. A total of 3,554 CMM patients from the Stockholm Melanoma Register were included.

HER3 expression is correlated to distally located and low-grade colon cancer.

Unlabelled: Background HER3 is a member of the human epidermal growth factor receptor complex (EGFR, HER2, HER3 and HER4). It has been investigated as a prognostic biomarker in colorectal cancer but is sparingly studied in colon cancer. HER3 can affect cellular proliferation, differentiation and migration in oncogenesis through ligand binding and activation of intracellular signal pathways.

HER3 expression in primary colorectal cancer including corresponding metastases in lymph node and liver.

Background: The human epidermal growth factor receptor complex (EGFR-1, HER2, HER3 and HER4) plays an important role in pathogenesis of solid tumours. We have previously reported high expression of HER3 in 70% of primary colorectal cancer (CRC) and that high expression were linked to a worse clinical outcome. The purpose of this study is to evaluate the HER3 expression in primary CRC and metastases.

The expression of CYP2W1 in colorectal primary tumors, corresponding lymph node metastases and liver metastases.

Introduction: Metastatic disease is a major cause of death in patients with colorectal cancer (CRC). We have previously investigated expression of an orphan cytochrome P450 (CYP) enzyme, CYP2W1, and found high expression in about one third of colorectal tumors. CYP2W1 has proven to metabolize duocarmycin analogs into cytotoxic substances, compounds that in xenografts of CRC cells expressing CYP2W1 completely inhibit tumor growth.

A combined analysis of mismatch repair status and thymidylate synthase expression in stage II and III colon cancer.

Unlabelled: This study in 716 colon cancer patients evaluates if a combined instead of a single marker analysis of mismatch repair (MMR) status and thymidylate synthase (TS) expression could individualize the treatment decision. The results indicate that a combined analysis of MMR status and TS expression can improve prediction of response to adjuvant 5-fluorouracil (5-FU)-based chemotherapy in stage III colon cancer.

Background: Colon cancer with mismatch repair deficiency and low TS expression has been associated with an improved prognosis.

The expression of CYP2W1: a prognostic marker in colon cancer.

Aim: The enzyme Cytochrome P450 2W1 (CYP2W1) is found in fetal colon tissue and is also detected in colorectal cancer but not in non-transformed tissue. In a pilot study, we reported that the immunohistochemically-detected expression of CYP2W1 might be of prognostic value since high expression of CYP2W1 was indicative of a worse prognosis. The aim of this study was to validate the pilot study's results using a larger, independent group of patients with colon cancer.

Mismatch repair protein expression is an independent prognostic factor in sporadic colorectal cancer.

Abstract Background. Mismatch repair (MMR) status has been reported as a prognostic and predictive factor in sporadic colorectal cancer (CRC). The purpose of this study was to determine the prognostic and predictive value of MMR protein expression in the adjuvant setting.

The expression of the novel CYP2W1 enzyme is an independent prognostic factor in colorectal cancer - a pilot study.

Aim: Cytochrome P450 (CYP) enzymes are important for drug metabolism. A novel cytochrome P450 enzyme, CYP2W1, has recently been identified. This enzyme is mainly found in foetal colon tissue and in tumour tissue.

Expression of thymidylate synthase in liver and lung metastases of colorectal cancer and their matched primary tumours.

Background: In advanced colorectal cancer (CRC) a low expression of thymidylate synthase (TS) in metastases predicts a higher response to 5-fluorouracil (5-FU). The purpose of this study was to investigate the expression of TS in liver and lung metastases of CRC and their matched primary tumours.

Patients And Methods: Immunohistochemical analysis of TS expression was performed on tissue samples of 48 CRC metastases (liver n=38, lung n=10) and their matched primary tumours (n=45).

The number of analyzed lymph nodes - a prognostic factor in colorectal cancer.

The prognostic significance of the number of lymph nodes examined in surgical specimen of colorectal cancer was determined. One thousand and twenty five patients with colorectal cancer stage II and III were included in the study. These patients underwent surgery from 1991 to 1997 and were enrolled in clinical trials to evaluate the efficacy of adjuvant 5-fluorouracil (5FU) based chemotherapy.

Detection of thymidylate synthase expression in lymph node metastases of colorectal cancer can improve the prognostic information.

Purpose: The level of thymidylate synthase (TS) in primary colorectal cancer (CRC) has been reported as a prognostic marker. The purpose of this study was to determine whether TS expression in lymph node metastases of Dukes' C CRC is a prognostic marker.

Patients And Methods: TS expression in the primary tumor and lymph node metastases from 348 patients with Dukes' C CRC was retrospectively assessed using immunohistochemistry and the monoclonal antibody TS 106.

Clinical effects of a chimeric anti-EpCAM monoclonal antibody in combination with granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.

The EpCAM antigen is highly expressed on colorectal carcinoma (CRC) cells. Murine anti-EpCAM MAb (anti-EpCAM mMAb) alone or in combination with cytokines may induce clinical responses including long-lasting complete remissions (CR) in patients with metastatic disease. The chimeric variant of anti-EpCAM MAb (anti-EpCAM cMAb) interacts more efficiently with human effector cells (ADCC) than the murine counterpart in the killing of colorectal carcinoma cells in vitro, an important mechanism of action for antibody in vivo.

Anti-EpCAM monoclonal antibody (MAb17-1A) based treatment combined with alpha-interferon, 5-fluorouracil and granulocyte-macrophage colony-stimulating factor in patients with metastatic colorectal carcinoma.

Monoclonal antibodies (MAbs) have different modes of action and toxicity profile compared to chemotherapeutics, which makes it interesting to combine these drugs. Addition of cytokines to MAb therapy may also augment immune effector functions utilized by MAb. In an effort to improve the therapeutic effect of a MAb-based regimen in colorectal carcinoma (CRC) patients, the effects of a combination of alpha-interferon (alpha-IFN), 5-fluorouracil (5-FU), granulocyte-macrophage colony-stimulating factor (GM-CSF) and mouse MAb17-1A was evaluated in 27 patients with metastatic disease.

5-FU split dose; a phase I/II and pharmacokinetic study of a different schedule of the Nordic regimen in advanced colorectal carcinoma.

Purpose: Despite more than four decades of fluoro-pyrimidine treatment in different cancers, the optimal schedule is still not known. The plasma half-life of 5-fluorouracil (5-FU) is extremely short and continuous infusion has gained popularity. In this study we explored whether repeated bolus 5-FU injections could improve the results.

Natural killer (NK) cell function is a strong prognostic factor in colorectal carcinoma patients treated with the monoclonal antibody 17-1A.

Tumor cells might be susceptible to different effector functions of the immune system. This cytotoxic capacity has been utilized to analyze the prognostic significance of peripheral blood mononuclear cells (PBMC) in patients with metastatic colorectal carcinoma (CRC) treated with the monoclonal antibody (MAb)17-1A. Such analysis might form the basis for future patient selection and may lead to improvements in therapeutic strategies.

Thymidylate synthase expression in rectal cancer and proliferation, assessed by cyclin A and Ki-67 expression.

Background: Levels of the enzyme thymidylate synthase (TS) are of prognostic significance in colorectal cancer. It may be argued that the levels of TS merely reflect the proliferative activity and could be replaced by markers of proliferation.

Materials And Methods: We used immunohistochemical approaches to examine the expression of TS, Cyclin A and Ki-67 in morphologically well-defined tumor areas in consecutive slices of rectal cancer, using the antibodies TS 106, NCL-Cyclin A and Mib-1.

MAb17-1A and cytokines for the treatment of patients with colorectal carcinoma.

CO17-1A/GA73-3/EpCam/KSA is a cellular adhesion molecule expressed on the majority of tumor cells in most patients with colorectal carcinoma. One of the first mouse monoclonal antibodies (MAbs) for therapeutic use was produced against this particular tumor associated antigen (MAb17-1A). MAb17-1A has served as a model for the development of antibody therapy.

Thymidylate synthase expression in colorectal cancer: a prognostic and predictive marker of benefit from adjuvant fluorouracil-based chemotherapy.

Purpose: We studied the prognostic value of thymidylate synthase (TS) expression in primary colorectal cancer (CRC) and the role of TS expression as a predictor of chemotherapeutic benefit in patients treated with adjuvant chemotherapy.

Patients And Methods: TS expression was immunohistochemically assessed on tumor sections from 862 patients with CRC Dukes' stages B and C enrolled onto randomized trials evaluating fluorouracil (5-FU)-based adjuvant chemotherapy.

Results: TS expression was an independent prognostic factor for disease-free (P =.