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MO04 - Lung Cancer Biology I (ID 86)
- Event: WCLC 2013
- Type: Mini Oral Abstract Session
- Track: Biology
- Presentations: 1
MO04.10 - Identification of biological properties of intralymphatic tumor related to the development of lymph node metastasis in lung adenocarcinoma (ID 1724)
16:15 - 17:45 | Author(s): K. Kirita
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.
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.
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.
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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