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R. Matsuwaki



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    MO04 - Lung Cancer Biology I (ID 86)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Biology
    • Presentations: 1
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      MO04.10 - Identification of biological properties of intralymphatic tumor related to the development of lymph node metastasis in lung adenocarcinoma (ID 1724)

      17:10 - 17:15  |  Author(s): R. Matsuwaki

      • Abstract
      • Presentation
      • Slides

      Background
      Intralymphatic tumors in the extratumoral area are considered to represent the preceding phase of lymph node (LN) metastasis. The aim of this study was to clarify the biological properties of intralymphatic tumors susceptible to the development of LN metastasis, with special reference to the expression of cancer initiating/stem cell (CIC/CSC) markers in cancer cells and the number of infiltrating stromal cells.

      Methods
      A total of 2087 consecutive adenocarcinoma patients underwent complete resections and systematic LN dissections between May 1998 and December 2012 were identified. Among these cases, we selected those that had been diagnosed as having lymphatic permeation in the extratumoral area (n = 107). We examined the expression levels of CIC/CSC related markers including ALDH1, OCT4, NANOG, SOX2 and Caveolin-1 in the intralymphatic and primary tumor cells to evaluate their relationship to LN metastasis. The number of infiltrating stromal cells expressing CD34, α-smooth muscle actin, and CD204 were also evaluated. Moreover, we measured E-cadherin expression to identify a correlation between CIC/CSC related molecules and epithelial - mesenchymal transition (EMT) process.

      Results
      Intrathoracic LN metastases were detected in specimens from 86 patients (80%). Among the intralymphatic tissues, low ALDH1 expression in cancer cells, high SOX2 expression in cancer cells, and a high number of CD204(+) macrophages were independent predictive factors for LN metastasis (odds ratio [95%CI] = 3.25 [1.11 – 9.82], P = 0.031 for ALDH1; 4.09 [1.38 – 13.4], P = 0.011 for SOX2; and 3.45 [1.16 – 11.4], P = 0.026 for CD204(+) macrophages). However, in the primary tumors, only a high SOX2 expression level in the cancer cells within the primary tumor was significantly correlated with LN metastasis (p=0.008); ALDH1 expression in the cancer cells and the number of CD204(+) macrophages were not correlated with LN metastasis (P = 0.230 and P = 0.088, respectively). Among these factors, only low ALDH1 expression in intralymphatic cancer cells was significantly correlated with the farther spreading of LN metastasis (mediastinal LN, pN2) (P = 0.046) and higher metastatic LN ratio (metastatic/resected) (P = 0.028). Intralymphatic cancer cells expressing low ALDH1 levels exhibited lower E-cadherin expression levels than cancer cells with high levels of ALDH1 expression (P = 0.015). The expressions of other CIC/CSC related markers, including OCT4, NANOG, SOX2, and Caveolin-1, were not correlated with the E-cadherin expression.

      Conclusion
      Intralymphatic cancer cells expressing low levels of ALDH1 and infiltrating macrophages expressing CD204 have a critical impact on LN metastasis. Especially, intralymphatic cancer cells expressing low levels of ALDH1 might acquire a metastatic aggressiveness by the EMT process. Our study highlighted the significance of evaluating the biological properties of intralymphatic tumors for tumor metastasis and suggested the possibility of usefulness as a new molecular target, especially as an adjuvant therapy.

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    MO26 - Anatomical Pathology II (ID 129)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO26.09 - Prognostic impact of CD204-positive macrophages in lung squamous cell carcinoma (ID 2023)

      11:15 - 11:20  |  Author(s): R. Matsuwaki

      • Abstract
      • Presentation
      • Slides

      Background
      Stromal cells, including macrophages, lymphocytes and fibroblasts, are known to interact with cancer cells and to produce a specific microenvironment capable of influencing tumor progression. Tumor-associated macrophages (TAMs) are recruited into cancer-induced stroma and produce a specific microenvironment for cancer progression. CD204 positive TAMs are reportedly related to tumor progression and clinical outcome in some tumors. The aim of this study was to clarify the correlation between CD204 positive TAMs and the clinicopathological features of lung squamous cell carcinoma.

      Methods
      We investigated the relationships between the numbers of CD204 positive TAMs and clinicopathological factors, microvessel density (MVD), and the numbers of Foxp3 positive lymphocytes in 208 consecutively resected cases. We also examined the relationships between the numbers of CD204 positive TAMs and the expression levels of cytokines involved in the migration and differentiation of CD204 positive TAMs.

      Results
      A high number of CD204 positive TAMs in the stroma was significantly correlated with an advanced p-stage, T factor, N factor, and the presence of vascular and pleural invasion. A high number of CD204 positive TAMs in the stroma was also a significant prognostic factor for all p-stages and p-stage I. Moreover, the numbers of CD204 positive TAMs were correlated with the MVD and the numbers of Foxp3 positive lymphocytes. A high number of CD204 positive TAMs was strongly correlated with the tissue expression level of MCP-1. CD204 positive TAMs were shown to be significant independent prognostic factors in a multivariate analysis.

      Conclusion
      CD204 positive TAMs were an independent prognostic factor in lung squamous cell carcinoma. CD204 positive TAMs, along with other tumor-promoting stromal cells such as regulatory T cells and endothelial cells, may create tumor-promoting microenvironments.

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    P1.12 - Poster Session 1 - NSCLC Early Stage (ID 203)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.12-007 - The Predictors of Early Recurrence in Patients with Completely Resected p-stage I Non-Small Cell Lung Cancer (ID 1256)

      09:30 - 09:30  |  Author(s): R. Matsuwaki

      • Abstract

      Background
      The objective of this study was to identify the risk factors for early (within 2 years after surgery) recurrence in patients with completely resected pathological stage I (p-stage I) non-small cell lung cancer (NSCLC).

      Methods
      We reviewed retrospectively 864 consecutive patients with p-stage I NSCLC who underwent complete resection between 1992 and 2012 at our institution. The correlation between clinicopathologic factors (sex, age, preoperative CEA level, tumor laterality, primary lobe, smoking history, histological type, histological differentiation, p-T status, lymphatic permeation, vascular invasion, pleural invasion) and early recurrence was evaluated using chi-square test and multivariate analysis.

      Results
      There were 498 men and 366 women, with an average age of 67 years. (range: 33-87). The median follow up period was 78 months. Histologically, 659 patients had adenocarcinomas, 189 squamous cell carcinomas, and 16 other types. T status was 1a in 230 patients, 1b in 274, and 2a in 360. Vascular invasion was observed in 326 patients, and lymphatic permeation in 169. Recurrence developed in 208 patients (24.1%), and 64 (7.4%) of them developed within 2 years after surgery. By multivariate analysis, vascular invasion (hazard ratio 3.441, 95% confidence interval 1.892-6.428) and moderate to poor differentiation (hazard ratio 3.252, 95% confidence interval 1.242-8.512) were shown to be independently significant risk factors for early recurrence. In patients with vascular invasion, distant failure occurred significantly more frequently than locoregional recurrence. The early recurrences were distant failure in 46 patients (72%). Of the 18 patients with locoregional recurrence only, 13 had malignant pleural effusion or pleural dissemination.

      Conclusion
      Moderate to poor differentiation and vascular invasion were the significant predictors of early recurrence within 2 years after complete resection of p-stage I NSCLC. More than 90% of the early recurrences were disseminated diseases. Therefore, adjuvant chemotherapy after complete resection may be beneficial for p-stage I NSCLC patients with vascular invasion or moderately to poorly differentiated tumors.