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Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma.

Matsuo Y, Kamitani T - PLoS ONE (2010)

Bottom Line: However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi.Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Center for Molecular Chaperone/Radiobiology and Cancer Virology, Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

ABSTRACT

Background: Melanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of alpha-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.

Methodology/principal findings: Recently, we found that human melanoma cell lines highly express alpha-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of alpha-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. alpha-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.

Conclusions/significance: The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

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Expression of α-synuclein in human malignant melanoma tissues.Tissue sections of 132 melanoma samples were immunostained with mouse monoclonal anti-α-synuclein antibody 4D6 (see text for identification of samples). The sections were then incubated with an alkaline phosphatase-conjugated anti-mouse IgG. After washing, Liquid Permanent Red substrate was used to develop the reaction and detect α-synuclein-positive cells. The sections were then counterstained with hematoxylin and analyzed by microscopy. The localization of α-synuclein is shown by the red color of Liquid Permanent Red substrate. Nuclear counterstaining is shown by the blue color of hematoxylin. Melanin pigments are brown in melanoma cells. Scale bar indicates 50 µm.
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pone-0010481-g004: Expression of α-synuclein in human malignant melanoma tissues.Tissue sections of 132 melanoma samples were immunostained with mouse monoclonal anti-α-synuclein antibody 4D6 (see text for identification of samples). The sections were then incubated with an alkaline phosphatase-conjugated anti-mouse IgG. After washing, Liquid Permanent Red substrate was used to develop the reaction and detect α-synuclein-positive cells. The sections were then counterstained with hematoxylin and analyzed by microscopy. The localization of α-synuclein is shown by the red color of Liquid Permanent Red substrate. Nuclear counterstaining is shown by the blue color of hematoxylin. Melanin pigments are brown in melanoma cells. Scale bar indicates 50 µm.

Mentions: Fig. 4 shows 9 of 132 samples of melanoma immunostainings. Panel A shows anti-α-synuclein immunostaining of primary melanoma (skin, face) from a 70-year-old female. α-Synuclein-positive, atypical melanoma cells are scattered in the dermis as well as infiltrating into the epidermis. The degree of pigmentation varies. Lymphocytic infiltration is present. Panel B shows immunostaining of primary melanoma (skin, trunk) from a 20-year-old female. There is nodular proliferation of melanoma cells in the nests without pigment production but with high expression of α-synuclein. Panel C shows immunostaining of primary melanoma (skin, left buttock) from a 55-year-old male. α-Synuclein-positive melanoma cells are proliferating in the dermis. Half of the melanoma cells generate melanin pigments. Vessel-like structures are observed. Panel D shows immunostaining of primary uveal melanoma (eyeball) from a 53-year-old male. Heavily pigmented melanoma cells can be seen. Some cells have less melanin pigments but express high levels of α-synuclein. Panel E shows immunostaining of primary melanoma (rectum) from a 38-year-old female. There is proliferation of spindle-shaped melanoma cells with α-synuclein expression but without pigment production. Panel F shows immunostaining of primary melanoma (anus) from a 77-year-old male. There is proliferation of melanoma cells with α-synuclein expression but without pigment production. Panel G shows immunostaining of metastatic melanoma (lymph node, right oxter) from a 44-year-old male. The lymph node is packed with round metastatic cells that express α-synuclein but do not produce melanin pigments. Panel H shows immunostaining of metastatic melanoma (lymph node, left groin) from a 72-year-old female. Metastatic melanoma cells are heavily pigmented in the lymph node. Some cells have less melanin pigments but express high levels of α-synuclein. Panel I shows immunostaining of metastatic melanoma (lung) from a 59-year-old male. Melanoma cells with α-synuclein expression but without brown melanin pigments are packed in the alveolar spaces, whereas melanoma cells with brown melanin pigments line on the alveolar walls. Nucleoli are prominent in melanoma cells.


Parkinson's disease-related protein, alpha-synuclein, in malignant melanoma.

Matsuo Y, Kamitani T - PLoS ONE (2010)

Expression of α-synuclein in human malignant melanoma tissues.Tissue sections of 132 melanoma samples were immunostained with mouse monoclonal anti-α-synuclein antibody 4D6 (see text for identification of samples). The sections were then incubated with an alkaline phosphatase-conjugated anti-mouse IgG. After washing, Liquid Permanent Red substrate was used to develop the reaction and detect α-synuclein-positive cells. The sections were then counterstained with hematoxylin and analyzed by microscopy. The localization of α-synuclein is shown by the red color of Liquid Permanent Red substrate. Nuclear counterstaining is shown by the blue color of hematoxylin. Melanin pigments are brown in melanoma cells. Scale bar indicates 50 µm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2864738&req=5

pone-0010481-g004: Expression of α-synuclein in human malignant melanoma tissues.Tissue sections of 132 melanoma samples were immunostained with mouse monoclonal anti-α-synuclein antibody 4D6 (see text for identification of samples). The sections were then incubated with an alkaline phosphatase-conjugated anti-mouse IgG. After washing, Liquid Permanent Red substrate was used to develop the reaction and detect α-synuclein-positive cells. The sections were then counterstained with hematoxylin and analyzed by microscopy. The localization of α-synuclein is shown by the red color of Liquid Permanent Red substrate. Nuclear counterstaining is shown by the blue color of hematoxylin. Melanin pigments are brown in melanoma cells. Scale bar indicates 50 µm.
Mentions: Fig. 4 shows 9 of 132 samples of melanoma immunostainings. Panel A shows anti-α-synuclein immunostaining of primary melanoma (skin, face) from a 70-year-old female. α-Synuclein-positive, atypical melanoma cells are scattered in the dermis as well as infiltrating into the epidermis. The degree of pigmentation varies. Lymphocytic infiltration is present. Panel B shows immunostaining of primary melanoma (skin, trunk) from a 20-year-old female. There is nodular proliferation of melanoma cells in the nests without pigment production but with high expression of α-synuclein. Panel C shows immunostaining of primary melanoma (skin, left buttock) from a 55-year-old male. α-Synuclein-positive melanoma cells are proliferating in the dermis. Half of the melanoma cells generate melanin pigments. Vessel-like structures are observed. Panel D shows immunostaining of primary uveal melanoma (eyeball) from a 53-year-old male. Heavily pigmented melanoma cells can be seen. Some cells have less melanin pigments but express high levels of α-synuclein. Panel E shows immunostaining of primary melanoma (rectum) from a 38-year-old female. There is proliferation of spindle-shaped melanoma cells with α-synuclein expression but without pigment production. Panel F shows immunostaining of primary melanoma (anus) from a 77-year-old male. There is proliferation of melanoma cells with α-synuclein expression but without pigment production. Panel G shows immunostaining of metastatic melanoma (lymph node, right oxter) from a 44-year-old male. The lymph node is packed with round metastatic cells that express α-synuclein but do not produce melanin pigments. Panel H shows immunostaining of metastatic melanoma (lymph node, left groin) from a 72-year-old female. Metastatic melanoma cells are heavily pigmented in the lymph node. Some cells have less melanin pigments but express high levels of α-synuclein. Panel I shows immunostaining of metastatic melanoma (lung) from a 59-year-old male. Melanoma cells with α-synuclein expression but without brown melanin pigments are packed in the alveolar spaces, whereas melanoma cells with brown melanin pigments line on the alveolar walls. Nucleoli are prominent in melanoma cells.

Bottom Line: However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi.Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Center for Molecular Chaperone/Radiobiology and Cancer Virology, Cancer Center, Medical College of Georgia, Augusta, Georgia, United States of America.

ABSTRACT

Background: Melanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of alpha-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.

Methodology/principal findings: Recently, we found that human melanoma cell lines highly express alpha-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of alpha-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. alpha-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, alpha-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.

Conclusions/significance: The Parkinson's disease-related protein, alpha-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although alpha-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.

Show MeSH
Related in: MedlinePlus