PMC4864781_01
a The invasive ductal breast carcinoma specimen that was resected when the patient was 32 years old (H&E). b The lung metastasis from breast cancer that was resected when the patient was 42 years old (H&E)
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Fig1
Images of the invasive ductal breast carcinoma that was resected when the patient was 32 years old and the lung metastasis from the breast cancer that was resected when the patient was 42 years old are shown in Fig. 1a and b, respectively.
PMC4864781_02
a On a hypopharyngeal fiberscopic image, a tumor was observed in the postcricoid area (a white arrow). b On a contrast-enhanced computed tomography scan of the neck before treatment, an enhanced tumor was observed in the postcricoid area of the hypopharynx (a white arrow). c On a fluorodeoxyglucose positron emission tomography scan of the neck before treatment, an enhanced tumor was observed in the hypopharynx (a black arrow) and the left side of the neck (arrowhead)
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Fig2
On hypopharyngoscopy, a tumor lesion was found in the left anterior wall of the hypopharynx, and the patient experienced bilateral vocal cord paralysis (Fig. 2a). A contrast-enhanced computed tomography (CT) scan of the neck revealed a 24-mm heterogeneously enhanced tumor that extended through the left anterior wall of the hypopharynx (Fig. 2b). There was no evidence of a primary lung tumor or other distant metastases (Fig. 2c).
Hematoxylin-eosin staining (H&E) and immunohistochemical studies. a Microscopic photos of the hypopharyngeal biopsy specimen (H&E). b The hypopharyngeal biopsy sample was diagnosed as metastatic breast carcinoma after positive ER immunostaining. c Microscopic photos of the lymph node specimen (H&E). d Positive ER immunostaining. e Positive progesterone receptor immunostaining. f Positive mammaglobin immunostaining
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Fig3
A pathologist analyzed the hypopharyngeal biopsy sample (Fig. 3a, b) and diagnosed the neck lymph node lesion as a hypopharyngeal metastasis from breast cancer. The biopsy sample was estrogen receptor (ER)-positive, progesterone receptor (PR)-positive, and human epidermal growth factor receptor type 2 (HER2)-negative (Fig. 3c-f).
a E-cadherin was expressed in the lymph node specimen. b Positive VEGF-A receptor immunostaining. c Positive VEGFR2 receptor immunostaining. d Electrophoresis of methylation-specific PCR products that were amplified using DNA from the lymph node specimen. The results show that only unmethylated alleles of CDH1 and VEGFR2 were detected. M methylated alleles, UnM unmethylated alleles, B water blank
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Fig4
On immunohistochemical analysis, the neck lymph node lesion strongly expressed E-cadherin (Fig. 4a), VEGF-A (Fig. 4b), and VEGFR2 (Fig. 4c). For E-cadherin and VEGFR2, only unmethylated alleles were detected (Fig. 4c).
DNA methylation and expression data from the TCGA database of invasive breast carcinoma. a Distribution of E-cadherin DNA methylation between breast cancer samples and normal samples (P < 0.005). b A representative result showing the inverse correlation between DNA methylation at the E-cadherin CpG site and E-cadherin expression in breast cancer. The Spearman rank correlation coefficient (corr) is shown. c Comparison of VEGFR2 gene expression in tumor samples and matched normal samples (P < 0.005). d The relationship between DNA methylation and mRNA expression of the VEGFR2 gene
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Fig5
DNA methylation and mRNA expression data for invasive breast carcinomas were collected from MethHC: a database of DNA methylation and gene expression in human cancer (http://methhc.mbc.nctu.edu.tw/php/index.php) in April 2016 (Fig. 5) (Huang et al.).