Thymidylate synthase genotyping is more predictive for therapy response than immunohistochemistry in patients with colon cancer.

Thymidylate synthase (TS) is a potentially valuable marker for therapy response since it is the molecular target of 5-fluorouracil (5-FU). TS can be analyzed at the DNA (gene polymorphisms and amplification) and protein level (immunohistochemistry). This study investigated the predictive role of TS at the DNA and protein levels in patients with N(+) colon cancer (n = 38).

Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer.

Background: The optimal treatment for locally recurrent rectal cancer (LRRC) is still a matter of debate. This study assessed the outcome of LRRC patients treated with multimodality treatment, consisting of neoadjuvant radio (chemo-) therapy, extended resection, and intraoperative radiotherapy.

Methods: One hundred and forty-seven consecutive patients with LRRC who underwent treatment between 1994 and 2006 were studied.

Circumferential margin involvement is the crucial prognostic factor after multimodality treatment in patients with locally advanced rectal carcinoma.

Purpose: After preoperative (radio)chemotherapy, histologic determinants for prognostication have changed. It is unclear which variables, including assessment of tumor regression, are the best indicators for local recurrence and survival.

Experimental Design: A series of 201 patients with locally advanced rectal cancer (cT3/T4, M0) presenting with an involved or at least threatened circumferential margin (CRM) on preoperative imaging (<2 mm) were evaluated using standard histopathologic variables and four different histologic regression systems.

Improvement of staging by combining tumor and treatment parameters: the value for prognostication in rectal cancer.

Background & Aims: Staging of cancer is based on the TNM system. This valuable system takes only tumor-related parameters into account, but in the era of refined surgery and preoperative therapy treatment-related factors are of equal importance. By using rectal cancer as a model we explored the hypothesis that a combination of tumor- and treatment-related parameters will result in improved prognostication.

Cyclooxygenase 2 expression in rectal cancer is of prognostic significance in patients receiving preoperative radiotherapy.

Purpose: To determine the effect of cyclooxygenase (COX)-2 expression on clinical behavior in irradiated and nonirradiated rectal carcinomas.

Experimental Design: Tumor samples were collected from 1,231 patients of the Dutch TME trial, in which rectal cancer patients were treated with standardized surgery and randomized for preoperative short-term (5 x 5 Gy) radiotherapy or no preoperative radiotherapy. Tissue microarrays were constructed from primary tumor material, and COX-2 expression was assessed by immunohistochemistry.

Loss of membranous Ep-CAM in budding colorectal carcinoma cells.

Tumor budding is a histological feature that reflects loss of adhesion of tumor cells and is associated with locoregional metastasis of colorectal carcinoma. Although nuclear localization of beta-catenin is associated with tumor budding, the molecular mechanism remains largely elusive. In this study, we hypothesize that the epithelial cell adhesion molecule (Ep-CAM) is involved in tumor budding.

Prognostic value of apoptosis in rectal cancer patients of the dutch total mesorectal excision trial: radiotherapy is redundant in intrinsically high-apoptotic tumors.

Purpose: The combination of radiotherapy and good quality surgery reduces local recurrence rate for rectal cancer patients. This study assesses the prognostic value of both intrinsic and radiotherapy-induced apoptosis and evaluates the relevance of radiotherapy for outcome of rectal cancer patients.

Experimental Design: Tumor samples (1,198) were available from the Dutch Total Mesorectal Excision trial, in which rectal cancer patients were treated with standardized surgery and randomized for preoperative short-term radiotherapy or not.

Loss of extracellular E-cadherin in the normal mucosa of duodenum and colon of patients with familial adenomatous polyposis.

The duodenum is the main site for (pre-) malignant extracolonic manifestations in patients with familial adenomatous polyposis (FAP). Changes in the E-cadherin/beta-catenin complex play a pivotal role in the development of malignancies. Loss of E-cadherin has been described in association with loss of SMAD4.