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Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer

  • Authors:
    • Yasuyoshi Miyata
    • Kensuke Mitsunari
    • Asai Akihiro
    • Shin‑Ichi Watanabe
    • Yasushi Mochizuki
    • Hideki Sakai
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki 852‑8501, Japan
    Copyright: © Miyata et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 287-294
    |
    Published online on: December 2, 2014
       https://doi.org/10.3892/mco.2014.471
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Abstract

Cigarette smoking is a major risk factor for urothelial cancer (UC) development. However, the associations between smoking and changes in the pathological characteristics and molecular expression of cancer‑related molecules in upper tract (UT) UC have not been fully elucidated. We investigated the associations between smoking status and cancer‑related factors, including cancer cell proliferation, apoptosis, angiogenesis, lymphangiogenesis and expression of vascular endothelial growth factor‑A and ‑C, matrix metalloproteinase (MMP)‑2 and ‑9, cyclooxygenase (COX)‑2 and urokinase‑type plasminogen activator, in patients with UTUC. A total of 134 patients who underwent nephroureterectomy were retrospectively investigated. Proliferation index (PI), microvessel density and lymphatic vessel density (LVD) were measured using anti‑Ki‑67, anti‑CD105 and anti‑D2‑40 antibodies in formalin‑fixed specimens. The apoptotic index was evaluated using the terminal deoxynucleotidyl transferase‑mediated dUTP nick end labeling method. Other cancer‑related molecules were investigated by immunohistochemistry in similar specimens. The patients were divided into three groups; non‑smoker (n=54, 40.3%), former smoker (n=46, 34.3%) and current smoker (n=34, 25.4%). The PI and the apoptotic index were not found to be correlated with smoking status; however, the mean/standard deviation level of LVD in current smokers (40.9/12.9) was significantly higher (P=0.034) compared to that in patients who had never smoked (34.4/10.6). In addition, smoking status was positively correlated with the presence of intratumoral lymphatic vessels (iLV) (P=0.010) and the expression of COX‑2 and MMP‑9 (P=0.032). The multivariate analysis demonstrated that current smoking was independently associated with all the abovementioned smoking‑related factors. However, former smoking was correlated with LVD and the presence of iLV. In the survival analysis, LVD, the presence of iLV and the expression of COX‑2 and MMP‑9 were identified as predictive factors for metastasis following surgery. In conclusion, lymphangiogenesis and the expression levels of COX‑2 and MMP‑9 were found to be associated with the smoking status of UTUC patients. Our results may provide important insights into the pathological changes precipitated by smoking in these patients.
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Copy and paste a formatted citation
Spandidos Publications style
Miyata Y, Mitsunari K, Akihiro A, Watanabe SI, Mochizuki Y and Sakai H: Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer. Mol Clin Oncol 3: 287-294, 2015.
APA
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., & Sakai, H. (2015). Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer. Molecular and Clinical Oncology, 3, 287-294. https://doi.org/10.3892/mco.2014.471
MLA
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., Sakai, H."Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer". Molecular and Clinical Oncology 3.2 (2015): 287-294.
Chicago
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., Sakai, H."Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer". Molecular and Clinical Oncology 3, no. 2 (2015): 287-294. https://doi.org/10.3892/mco.2014.471
Copy and paste a formatted citation
x
Spandidos Publications style
Miyata Y, Mitsunari K, Akihiro A, Watanabe SI, Mochizuki Y and Sakai H: Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer. Mol Clin Oncol 3: 287-294, 2015.
APA
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., & Sakai, H. (2015). Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer. Molecular and Clinical Oncology, 3, 287-294. https://doi.org/10.3892/mco.2014.471
MLA
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., Sakai, H."Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer". Molecular and Clinical Oncology 3.2 (2015): 287-294.
Chicago
Miyata, Y., Mitsunari, K., Akihiro, A., Watanabe, S., Mochizuki, Y., Sakai, H."Smoking-induced changes in cancer‑related factors in patients with upper tract urothelial cancer". Molecular and Clinical Oncology 3, no. 2 (2015): 287-294. https://doi.org/10.3892/mco.2014.471
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