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Clinical significance of aberrant Wnt7a promoter methylation in human non-small cell lung cancer in Koreans.

Kim TH, Moon JY, Kim SH, Paik SS, Yoon HJ, Shin DH, Park SS, Sohn JW - J. Korean Med. Sci. (2015)

Bottom Line: In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001).However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit.Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

ABSTRACT
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

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Related in: MedlinePlus

Examples of Immunohistochemical analysis of E-cadherin protein expression in lung cancer tissues. (A) trace, (B) low, (C) intermediate, (D) strong expression of E-cadherin (magnification, ×100).
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Figure 1: Examples of Immunohistochemical analysis of E-cadherin protein expression in lung cancer tissues. (A) trace, (B) low, (C) intermediate, (D) strong expression of E-cadherin (magnification, ×100).

Mentions: The tissue sections were scored semiquantitatively for membrane and cytoplasmic staining by light microscopy. Labeling scores were determined by multiplying the percentage of positive tumor cells per slide (0% to 100%) by the dominant staining intensity (0=negative, 1=trace, 2=weak, 3=intermediate, 4=strong). Resulting scores ranged from 0-400. Specimens with overall scores of 5-100, 101-200, 201-300, and 301-400 were classified as trace, low-level, intermediate-level, and high-level expression, respectively. Specimens exhibiting a complete absence of staining or faint staining in less than 5% of the cells were classified as negative (Fig. 1). All samples were evaluated and scored by specialized pathologist randomly without knowledge of the patient's clinical information.


Clinical significance of aberrant Wnt7a promoter methylation in human non-small cell lung cancer in Koreans.

Kim TH, Moon JY, Kim SH, Paik SS, Yoon HJ, Shin DH, Park SS, Sohn JW - J. Korean Med. Sci. (2015)

Examples of Immunohistochemical analysis of E-cadherin protein expression in lung cancer tissues. (A) trace, (B) low, (C) intermediate, (D) strong expression of E-cadherin (magnification, ×100).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4310941&req=5

Figure 1: Examples of Immunohistochemical analysis of E-cadherin protein expression in lung cancer tissues. (A) trace, (B) low, (C) intermediate, (D) strong expression of E-cadherin (magnification, ×100).
Mentions: The tissue sections were scored semiquantitatively for membrane and cytoplasmic staining by light microscopy. Labeling scores were determined by multiplying the percentage of positive tumor cells per slide (0% to 100%) by the dominant staining intensity (0=negative, 1=trace, 2=weak, 3=intermediate, 4=strong). Resulting scores ranged from 0-400. Specimens with overall scores of 5-100, 101-200, 201-300, and 301-400 were classified as trace, low-level, intermediate-level, and high-level expression, respectively. Specimens exhibiting a complete absence of staining or faint staining in less than 5% of the cells were classified as negative (Fig. 1). All samples were evaluated and scored by specialized pathologist randomly without knowledge of the patient's clinical information.

Bottom Line: In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001).However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit.Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea.

ABSTRACT
The Wnt signaling pathway has regulatory roles in cell proliferation, differentiation, and polarity. Aberrant Wnt pathway regulation can lead to abnormal cell proliferation and cancer, and loss of Wnt7a expression has been demonstrated in lung cancer cell lines. E-cadherin keeps intercellular integrity and prevents metastasis. Therefore, E-cadherin has been known as a prognostic factor in cancer. In the present study, we investigated the E-cadherin expression status by immunohistochemical stain and the Wnt7a promoter methylation status in human non-small cell lung carcinoma (NSCLC) by methylation-specific PCR. We also analyzed their correlations with clinicopathological factors. Methylation of the Wnt7a gene promoter was detected in the lung tissues of 32 of 121 (26.4%) patients with NSCLC. Wnt7a promoter methylation was correlated with advanced tumor stage (P = 0.036) and distant metastasis (P = 0.037). In addition, Wnt7a promoter methylation showed correlation with loss of E-cadherin expression (P < 0.001). However, Wnt7a promoter methylation was not closely related with gender, age, histological type, or smoking habit. Even though Wnt7a methylation could not show significant correlation with the long term survival of the patients with limited follow up data, these findings suggest that loss of the Wnt7a gene induced by promoter methylation might be another prognostic factor for NSCLC and that restoration of Wnt7a may be a promising treatment for NSCLC.

Show MeSH
Related in: MedlinePlus