Proteins of the VEGFR and EGFR pathway as predictive markers for adjuvant treatment in patients with stage II/III colorectal cancer: results of the FOGT-4 trial.

BACKGROUND: Unlike metastatic colorectal cancer (CRC) there are to date few reports concerning the predictive value of molecular biomarkers on the clinical outcome in stage II/III CRC patients receiving adjuvant chemotherapy. Aim of this study was to assess the predictive value of proteins related with the EGFR- and VEGFR- signalling cascades in these patients. METHODS: The patients' data examined in this study were from the collective of the 5-FU/FA versus 5-FU/FA/irinotecan phase III FOGT-4 trial. Tumor tissues were stained by immunohistochemistry for VEGF-C, VEGF-D, VEGFR-3, Hif-1 α, PTEN, AREG and EREG expression and evaluated by two independent, blinded investigators. RESULTS: Patients with negative AREG and EREG expression on their tumor had a significant longer DFS in comparison to AREG/EREG positive ones (p< 0.05). The benefit on DFS in AREG-/EREG- patients was even stronger in the group that received 5-FU/FA/irinotecan as adjuvant treatment (p=0.002). Patients with strong expression of PTEN profited more in terms of OS under adjuvant treatment containing irinotecan (p< 0.05). Regarding markers of the VEGFR- pathway we found no correlation of VEGF-C- and VEGFR-3 expression with clinical outcome. Patients with negative VEGF-D expression had a trend to live longer when treated with 5-FU/FA (p=0.106). Patients who were negative for Hif-1 α, were disease-free in more than 50% at the end of the study and showed significant longer DFS-rates than those positive for Hif-1 α (p=0.007). This benefit was even stronger at the group treated with 5-FU/FA/irinotecan (p=0.026). Finally, AREG-/EREG-/PTEN+ patients showed a trend to live longer under combined treatment combination. CONCLUSIONS: The addition of irinotecan to adjuvant treatment with 5-FU/FA does not provide OS or DFS benefit in patients with stage II/III CRC. Nevertheless, AREG/EREG negative, PTEN positive and Hif-1 α negative patients might profit significantly in terms of DFS from a treatment containing fluoropyrimidines and irinotecan. Our results suggest a predictive value of these biomarkers concerning adjuvant chemotherapy with 5-FU/FA +/- irinotecan in stage II/III colorectal cancer.

Adult onset of T-cell deficiency with impaired CD2 expression complicated by Rhodococcus infection: a case report.

BACKGROUND: The functional importance of CD2 in vivo is currently the subject of discussion. OBJECTIVE: To describe a 47-year-old white man with systemic Rhodococcus infection, a rarely observed opportunistic disease, secondary to severe lymphopenia. METHODS: We extensively characterized lymphocyte phenotype and function. RESULTS: Both CD4+ and CD8+ T cells were severely diminished, with a particular reduction in alpha:beta T cells. Human immunodeficiency virus infection was excluded. CD2 expression was decreased not only on T cells but also on nonaffected natural killer cells. Production of interferon-gamma interleukin 2, and tumor necrosis factor a was normal. Neither B-cell numbers nor humoral immune responses were affected. In addition, adhesion molecules CD11a, CD54, and CD154 were normally expressed, as were the costimulatory molecules CD28, CD80, and CD86. CONCLUSIONS: We hypothesize that prolonged disturbance of CD2 expression led to an acquired severe cellular immunodeficiency. This underlines the importance of CD2 in vivo, where it may play a role in the fine regulation of T-cell proliferation.