Clinical implications of DLL4 expression in gastric cancer

BACKGROUND: Delta-like ligand 4 (DLL4)-Notch signaling plays a key role in tumor neovascular development and angiogenesis during tumor growth. The clinical significance of DLL4 expression in gastric cancer has not been clarified. METHODS: Gastric cancer cell lines and 180 gastric cancer patients were enrolled. DLL4 expression in gastric cancer cells and stroma was identified and evaluated immunohistochemically. The association between DLL4 and clinicopathological factors was also assessed. RESULTS: DLL4 expression was identified in the cellular membrane and cytoplasm of gastric cancer cells by immunoblotting and immunohistochemical staining. DLL4 positivity in cancer cells and stroma was found in 88 (48%) and 41 (22%) of the 180 gastric cancer patients respectively. Both cancer and stromal DLL4 expression significantly correlated with more advanced tumor depth, nodal involvement, and lymphatic and venous invasion. A strongly positive association between cancerous and stromal DLL4 expression was identified (p < 0.01). Both cancerous and stromal DLL4 expression were prognostic markers in gastric cancer as determined by univariate analysis. CONCLUSIONS: Cancerous and stromal DLL4 expression was found in 48% and 22% in gastric cancer, and significantly affected postoperative clinical outcomes. Cancerous and stromal DLL4 expression may be an effective target of anti-DLL4 treatment in gastric cancer

Utility of the sentinel node concept for detection of lateral pelvic lymph node metastasis in lower rectal cancer

Abstract Background There are two lymphatic flows in lower rectal cancer; one along the inferior mesenteric artery and another towards the internal iliac artery. The benefit of dissection of lateral pelvic (LP) lymph nodes (LPLN) remains controversial. This study aimed to clarify the possibility of detecting the sentinel node (SN) of the LP region (LPSN) and examine metastasis, including micrometastasis, using a radio isotope (RI) method. Methods In total, 62 patients with clinical (c)T1-T4 rectal cancer were enrolled in this study (11, 16 and 35 patients had tumor located in the upper, middle and lower rectal third, respectively). LPSNs were detected using a radio-isotope method in which 99 m technetium-tin colloid was endoscopically injected into the submucosa in patients with cT1, and into the muscularis propria in patients with cT2, cT3 and cT4. All patients underwent curative resection with lymphadenectomy. LPSN metastases were diagnosed by HE staining, immunohistochemical staining using AE1/AE3 as a primary antibody and by RT-PCR using CEA as a marker. Results Of the lower rectal (c)T2–4 tumors, 38.4% had lateral pelvic lymphatic flow that was significantly greater than that of cT1 tumors in the upper and middle thirds of the rectum (p = 0.0074). HE and immunohistochemical staining did not detect LPSN metastases but RT-PCR detected micrometastasis of three SNs. The remaining half of LPSNs were immunohistochemically re-examined; in all three cases, isolated tumor cells were detected. Conclusion The SN concept may be useful for detecting lateral pelvic lymphatic flow and LPSN metastases, including micrometastasis in lower rectal cancer

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis

Esophageal cancer is among the most aggressive diseases, and circulating tumor cells (CTCs) have been recognized as novel biomarkers for various cancers over the past two decades, including esophageal cancer. CTCs might provide crucial clinical information for predicting cancer prognosis, monitoring therapeutic responses or recurrences, or elucidating the mechanism of metastasis. The isolation of CTCs is among the applications of a &ldquo;liquid biopsy&rdquo;. There are various technologies for liquid biopsies, and they are classified into two main methods: cytometric or non-cytometric techniques. Here, we review a total of 57 eligible articles to summarize various technologies for the use of a liquid biopsy in esophageal cancer and perform a meta-analysis to assess the clinical utility of liquid biopsies as a prognostic and diagnostic biomarker technique. For prognostic evaluation, the pooled hazard ratio in the cytometric assay is relatively higher than that of the non-cytometric assay. On the other hand, a combination of multiple molecules, using a non-cytometric assay, might be a favorable biomarker technique for the early diagnosis of esophageal cancer. Although determining strong evidence for a biomarker by using a liquid biopsy is still challenging, our meta-analysis might be a milestone for the future development of liquid biopsies in use with esophageal cancer