The radiologic criteria of a consolidation/tumor ratio 0.25 or less in cT1a (≤2.0 cm) and 0.50 in cT1a-b (≤3.0 cm) were both able to define a homogeneous group of patients with an excellent prognosis before surgery.

Recent studies have reported increased podoplanin expression by cancer cells and stromal cells, but little is known about its expression and biological significance in adenocarcinoma of the lung. We examined podoplanin expression by both cancer cells and stromal cells in 177 consecutive lung adenocarcinoma cases and analyzed relations between podoplanin expression and both clinicopathological factors and outcome. Podoplanin expression was observed on the apical membrane of the cancer cells in only 9 of the 177 (5.1%) cases. By contrast, cancer-associated fibroblasts (CAFs) were found to express podoplanin in 54 cases (30.5%). Podoplanin (1) CAFs were found only in invasive adenocarcinoma and none were found in noninvasive adenocarcinoma. Conventional prognostic factors were significantly correlated with podoplanin expression by CAFs. The univariate analyses and log-rank test showed that podoplanin expression was significantly associated with shorter survival time (p < 0.001 and p < 0.001, respectively). We divided the cases into 3 groups according grade based on the proportion of CAFs expressing podoplanin [a grade 0 group (n 5 123), a grade 1 group (n 5 36) and a grade 2 group (n 5 18)]. The result showed that conventional prognostic factors were significantly correlated with the grade of podoplanin expression by CAFs. Furthermore, the grade 2 group tended to have a shorter survival time than the grade 1 group (p 5 0.092). The results of this study highlight the importance of podoplanin expression by CAFs and provide new insights into the biology of the cancer microenvironment in adenocarcinoma of the lung.

Background: Tumor tissue is composed of variable numbers of cancer cells and stromal cells, and tumor-associated macrophages are recruited into cancer-induced stroma and produce a specific microenvironment. Alternatively, activated macrophages (M2 phenotype) are known to be related to tumor progression and outcome, and CD204 has been reported to be expressed in M2 macrophages in some tumors. Methods: To investigate whether CD204-positive macrophages reflect tumor aggressiveness in adenocarcinoma of the lung, we investigated the relationships between the numbers of CD204positive stromal macrophages and both clinicopathological features and outcome in 170 consecutive resected cases. We also examined the relationships between the numbers of CD204-positive macrophages and the expression levels of cytokines involved in the migration and differentiation of M2 macrophages. Results:The numbers of CD204-positive macrophages were significantly correlated with several prognostic factors. The log-rank test showed a significant association between the numbers of CD204positive macrophages and a poor outcome (p ϭ 0.0073), whereas the numbers of macrophages expressing CD68, a pan-macrophage/ monocyte marker, were of marginal prognostic significance (p ϭ 0.0789). We evaluated associations between the levels of expression of the cytokines IL-6, IL-10, IL-12a, IL-12b, M-colony-stimulating factor, IFN-gamma-., and monocyte chemoattractant protein-1 in cancer tissue and the numbers of CD204-positive macrophages. The expression levels of IL-10 and monocyte chemoattractant protein-1, which are involved in differentiation, accumulation, and migration of M2 macrophages, were significantly correlated with the numbers of CD204-positive macrophages (p ϭ 0.031 and p ϭ 0.031, respectively). Conclusion: These findings demonstrated that CD204-positive macrophages clearly reflect the tumor-promoting phenotype of tumorassociated macrophages in lung adenocarcinoma.

R0 resection is essential for prolonged OS for surgically treated thymic carcinoma, but maximal debulking surgery might be beneficial and worth evaluating for advanced disease deemed difficult for R0 resection. The benefit of postoperative radiotherapy after R0 resection should also be evaluated prospectively.

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