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Article Open Access

Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma

  • Authors:
    • Bing‑Sheng Sun
    • Bao‑Xiang Pei
    • Kang Zhang
    • Lu‑Chang Zhang
    • Guang‑Jing Zhang
    • Ji‑Kuan Liu
    • Hong‑Wei Cui
    • Fen Pan
    • Zhen‑Fa Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin Lung Cancer Center, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin 300060, P.R. China, Department of Thoracic Surgery, Jining No. 1 People's Hospital, Jining, Shandong 272011, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4467-4476
    |
    Published online on: October 17, 2016
       https://doi.org/10.3892/ol.2016.5270
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Abstract

Stepwise progression from adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) to lepidic predominant adenocarcinoma (LPA) was proposed by various scholars. Interstitial tumor‑associated macrophages (TAMs) and various potential chemokines involved in the progression from AIS/MIA to LPA were hypothesized. In the present study, immunohistochemistry or immunofluorescent double staining was used to detect the expression of the TAMs marker cluster of differentiation (CD) 68, tumor‑derived colony‑stimulating factor (CSF)‑1, interleukin (IL)‑6, matrix metalloproteinase (MMP)‑2, E‑cadherin and Snail in lung adenocarcinoma specimens, including AIS/MIA, LPA and other types. It was observed that infiltrating TAMs were negatively associated with the prognosis of patients, and that the infiltration degree of interstitial TAMs was higher in LPA than that in AIS/MIA. In addition, E‑cadherin, Snail and MMP‑2 expression were significantly correlated with the infiltration degree of TAMs. Survival analysis revealed that co‑expression of CD68, CSF‑1 and IL‑6 was an independent prognostic factor. Stratified analysis demonstrated that, in AIS/MIA patients, there was a statistically significant difference between the number of TAMs (TAMs ≤25 and TAMs >25) in the CD68+CSF‑1+IL‑6+ group compared with other groups (including CD68+CSF‑1‑IL‑6‑, CD68+CSF‑1+IL‑6‑, CD68+CSF‑1‑IL‑6+ and CD68‑ groups). By contrast, in patients with TAMs >25 and in patients with positive CD68, CSF‑1 and IL‑6 expression, the survival rates were not significantly different between AIS/MIA and LPA. These results suggested that co‑expression of TAMs marker CD68, CSF‑1 and IL‑6 may be a valuable independent prognostic predictor in lung adenocarcinoma. TAMs may facilitate AIS/MIA progression to LPA, which may be closely associated with the induction of the epithelial-mesenchymal transition.
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Copy and paste a formatted citation
Spandidos Publications style
Sun BS, Pei BX, Zhang K, Zhang LC, Zhang GJ, Liu JK, Cui HW, Pan F and Zhang ZF: Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma. Oncol Lett 12: 4467-4476, 2016.
APA
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J. ... Zhang, Z. (2016). Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma. Oncology Letters, 12, 4467-4476. https://doi.org/10.3892/ol.2016.5270
MLA
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J., Cui, H., Pan, F., Zhang, Z."Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma". Oncology Letters 12.6 (2016): 4467-4476.
Chicago
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J., Cui, H., Pan, F., Zhang, Z."Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma". Oncology Letters 12, no. 6 (2016): 4467-4476. https://doi.org/10.3892/ol.2016.5270
Copy and paste a formatted citation
x
Spandidos Publications style
Sun BS, Pei BX, Zhang K, Zhang LC, Zhang GJ, Liu JK, Cui HW, Pan F and Zhang ZF: Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma. Oncol Lett 12: 4467-4476, 2016.
APA
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J. ... Zhang, Z. (2016). Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma. Oncology Letters, 12, 4467-4476. https://doi.org/10.3892/ol.2016.5270
MLA
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J., Cui, H., Pan, F., Zhang, Z."Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma". Oncology Letters 12.6 (2016): 4467-4476.
Chicago
Sun, B., Pei, B., Zhang, K., Zhang, L., Zhang, G., Liu, J., Cui, H., Pan, F., Zhang, Z."Significance of interstitial tumor-associated macrophages in the progression of lung adenocarcinoma". Oncology Letters 12, no. 6 (2016): 4467-4476. https://doi.org/10.3892/ol.2016.5270
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