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Tumor-associated macrophages (TAMs) are key components of the tumor microenvironment that can be polarized into different phenotypes, including tumor-inhibiting M1 macrophages and tumor-promoting M2 macrophages. To elucidate the biological and clinical significance of M2 TAMs in non-small-cell lung cancer (NSCLC), a comprehensive clinical assessment of the tissue distribution of M2 TAMs was performed. The tissue distribution of M2 TAMs was retrospectively analyzed using CD163 immunohistochemistry in 160 consecutive patients who underwent NSCLC resection. Tumor proliferation was evaluated via the Ki-67 proliferation index. The results revealed that the stromal density of M2 TAMs was significantly associated with the C-reactive protein (CRP) level (P=0.0250), the Ki-67 proliferation index (P=0.0090) and invasive size (P=0.0285). Furthermore, the stromal M2 TAM density was significantly associated with tumor differentiation (P=0.0018), lymph node metastasis (P=0.0347) and pathological stage (P=0.0412). The alveolar M2 TAM density was also significantly associated with the CRP level (P= 0.0309), invasive size (P<0.0001), tumor differentiation (P=0.0192), tumor status (P=0.0108) and pathological stage (P=0.0110). By contrast, no association was observed between islet M2 TAM density and the aforementioned biological and clinical factors. In regards to prognosis, disease-free survival rate was significantly lower in patients with stromal M2 TAM-high tumors (P=0.0270) and in those with alveolar M2 TAM-high tumors (P=0.0283). Furthermore, the overall survival rate was also significantly lower in patients with stromal M2 TAM-high tumors (P=0.0162) and in those with alveolar M2 TAM-high tumors (P=0.0225). Therefore, during NSCLC progression, M2 TAMs may induce tumor cell aggressiveness and proliferation and increase metastatic potential, resulting in a poor prognosis in patients with NSCLC.

p21 expression was shown to be an independent prognostic factor in NSCLC.

This study showed an excellent long-term prognosis following ER of patients with rectal NETs, confirming that ER is a valid treatment option for small rectal NETs. The present study also revealed highly prevalent lymphovascular invasion even in minute rectal NETs; this observation raises a question regarding its significance as a risk factor for metastasis.

Purpose:The purpose is to assess clinical significance of matrix metalloproteinase (MMP)-2 and MMP-9 status, especially MMP-2 status, in stromal cells in non-small-cell lung cancer (NSCLC) because experimental studies have revealed that stromal MMP-2 plays important roles in progression of malignant tumors, but most clinical studies focused on tumoral MMP-2 expression, not stromal MMP-2 expression.Experimental Design: We conducted a retrospective study on MMP-2 and MMP-9 expression as evaluated immunohistochemically in a total of 218 consecutive patients with completely resected pathological stage I-IIIA, NSCLC.Results: Strong MMP-2 expression in tumor cells and stromal fibroblasts were documented in 54 (24.8%) and 132 (60.6%) patients, respectively. Strong MMP-2 expression in stromal fibroblasts was more frequently seen in squamous cell carcinoma (72.7%) than in adenocarcinoma (54.9%; P ‫؍‬ 0.016). Tumors showing strong MMP-2 expression in stromal fibroblasts showed a significantly higher intratumoral microvessel density (IMVD) than weak stromal MMP-2 tumors (mean intratumoral microvessel density, 50.9 versus 32.4, P ‫؍‬ 0.003). In addition, postoperative prognosis of strong stromal MMP-2 patients was significantly poorer than that of weak stromal MMP-2 patients (5-year survival rate, 77.5 versus 60.2%, P ‫؍‬ 0.032), and the prognostic significance was enhanced in squamous cell carcinoma patients but disappeared in adenocarcinoma patients. Multivariate analyses confirmed that strong stromal MMP-2 expression was a significant factor to predict a poor prognosis in squamous cell carcinoma patients, not in adenocarcinoma patients. In contrast, MMP-2 or MMP-9 status in tumor cells was not a significant prognostic factor.Conclusions: MMP-2 status in stromal fibroblasts, not in tumor cells, was a significant prognostic factor associated with angiogenesis in NSCLC.

Background and Aim:In recent years, the effectiveness of colorectal endoscopic submucosal dissection (ESD) has been increasingly reported. Herein, we highlight the most recent developments and technical advantages of colorectal ESD compared to EMR and minimally invasive surgery.Methods: All candidate lesions for ESD were confirmed as being intramucosal tumors by colonoscopy. Presently, the indications for colorectal ESD approved by the Japanese government's medical insurance system are early colorectal cancers with a maximum tumor size of 2-5 cm; however, many early cancers >5 cm have been treated by ESD in referral centers. Results:The primary advantage of ESD compared to endoscopic mucosal resection (EMR) is a higher en-bloc resection rate for large colonic tumors that had previously been treated by surgery. ESD has several advantages compared to other therapeutic modalities, such as being a safer technique and providing better quality of life. For rectal cancer treatment, a longer procedure time is required for laparoscopic assisted colectomy, whereas trans-anal resection and trans-anal endoscopic microsurgery are more invasive than ESD with a significantly higher recurrence rate. Accordingly, ESD is the preferred choice for early colorectal cancers when there is no risk of lymph-node metastasis. Conclusion:ESD is an effective procedure for treating noninvasive non-polypoid colorectal tumors. These tumors may be difficult to resect en bloc by conventional EMR. The use of ESD results in a higher en-bloc resection rate and is less invasive than surgery.

Background: Immunochemical fecal occult blood test (iFOBT) is widely used for colorectal cancer screening; however, its sensitivity is insufficient. We recently reported a fecal microRNA (miRNA) test (FmiRT) to detect colorectal cancer. In this study, we investigated a new colorectal cancer screening method combining iFOBT and FmiRT to improve the sensitivity compared with iFOBT alone.Methods: In total, 117 colorectal cancer patients and 107 healthy volunteers were enrolled. Ten-milligram fecal samples were collected and iFOBT was conducted. Fecal RNA was extracted from residuum of iFOBT and then the expression of 14 kinds of miRNA was analyzed for the FmiRT using real-time reverse transcription PCR.Results: Levels of fecal miR-106a expression in iFOBTþ patients and iFOBTÀ patients were significantly higher than in healthy volunteers (P ¼ 0.001). The sensitivity and specificity of FmiRT using miR-106a were 34.2% and 97.2%, and those of iFOBT were 60.7% and 98.1%, respectively. The overall sensitivity and specificity of the new screening method combining iFOBT and FmiRT were 70.9% and 96.3%, respectively. One quarter of colorectal cancer patients with false-negative iFOBT seemed to be true positive upon adding FmiRT using fecal miR-106a.Conclusions: Fecal miR-106a is a good molecular marker to identify colorectal cancer patients from among those with negative iFOBT results. FmiRT combined with iFOBT may improve the sensitivity to detect colorectal cancer.Impact: We have shown the usefulness of fecal miR-106a to detect the colorectal cancer patients among those with negative iFOBT results. Cancer Epidemiol Biomarkers Prev; 22(10); 1844-52. Ó2013 AACR.