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Emerging clinical applications of selected biomarkers in melanoma.

Tetzlaff MT, Torres-Cabala CA, Pattanaprichakul P, Rapini RP, Prieto VG, Curry JL - Clin Cosmet Investig Dermatol (2015)

Bottom Line: Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease.This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status.The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
Melanoma is a lethal skin disease with a mostly predictable clinical course according to a known constellation of clinical and pathologic features. The distinction of melanoma from benign melanocytic nevus is typically unequivocol; however, there is a subset of tumors known for its diagnostic challenges, development of late metastases, and difficulties in treatment. Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease. This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status. The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.

No MeSH data available.


Related in: MedlinePlus

Immunohistochemcial evaluation of BAP-1 and BRAFV600E status in melanocytic lesions.Notes: (A) Melanocytic nevus composed of sheets of epithelioid-shaped melanocytes in the dermis (H&E stain, ×400); (B) Anti-BAP-1 demonstrates loss of nuclear expression in melanocytes (arrows) indicative of the presence of BAP-1 mutation (IHC stain, ×400); (C) Diffuse cytoplasmic expression of anti-BRAFV600E (IHC stain, ×400).Abbreviations: H&E, hematoxylin and eosin; IHC, immunohistochemistry.
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f7-ccid-8-035: Immunohistochemcial evaluation of BAP-1 and BRAFV600E status in melanocytic lesions.Notes: (A) Melanocytic nevus composed of sheets of epithelioid-shaped melanocytes in the dermis (H&E stain, ×400); (B) Anti-BAP-1 demonstrates loss of nuclear expression in melanocytes (arrows) indicative of the presence of BAP-1 mutation (IHC stain, ×400); (C) Diffuse cytoplasmic expression of anti-BRAFV600E (IHC stain, ×400).Abbreviations: H&E, hematoxylin and eosin; IHC, immunohistochemistry.

Mentions: BAP-1 (BCRA1 associated protein-1) protein is an ubiquitin hydrolase that binds to BRCA1 and functions as a tumor suppressor.83 Germline mutations in BAP-1 have been described that predispose affected family members to uveal and cutaneous melanomas and development of melanocytic lesions with distinct clinical and histologic features.84,85 Affected individuals present with multiple (range 5–50 lesions) well-circumscribed dome-shaped papules near the second decade of life.84,85 Histologically, the melanocytic lesions are located predominantly in the dermis and are composed of epithelioid melanocytes with abundant cytoplasm and distinct nucleoli. The lesions demonstrate similar cytologic features seen with Spitz nevi (Figure 7A). Similar lesions develop in the context of somatically acquired BAP-1 loss. IHC analysis with anti-BAP-1 demonstrates loss of nuclear staining in melanocytic lesions with BAP-1 mutations (Figure 7B). Furthermore, a significant proportion of BAP-1 lesions also frequently harbor a BRAFV600E mutation (Figure 7C). The combined features of BRAFV600E expression and loss of BAP-1 constitutes a distinct subset of Spitz nevi analogous to those harboring gains in chromosome 11p together with HRAS mutation.86


Emerging clinical applications of selected biomarkers in melanoma.

Tetzlaff MT, Torres-Cabala CA, Pattanaprichakul P, Rapini RP, Prieto VG, Curry JL - Clin Cosmet Investig Dermatol (2015)

Immunohistochemcial evaluation of BAP-1 and BRAFV600E status in melanocytic lesions.Notes: (A) Melanocytic nevus composed of sheets of epithelioid-shaped melanocytes in the dermis (H&E stain, ×400); (B) Anti-BAP-1 demonstrates loss of nuclear expression in melanocytes (arrows) indicative of the presence of BAP-1 mutation (IHC stain, ×400); (C) Diffuse cytoplasmic expression of anti-BRAFV600E (IHC stain, ×400).Abbreviations: H&E, hematoxylin and eosin; IHC, immunohistochemistry.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321413&req=5

f7-ccid-8-035: Immunohistochemcial evaluation of BAP-1 and BRAFV600E status in melanocytic lesions.Notes: (A) Melanocytic nevus composed of sheets of epithelioid-shaped melanocytes in the dermis (H&E stain, ×400); (B) Anti-BAP-1 demonstrates loss of nuclear expression in melanocytes (arrows) indicative of the presence of BAP-1 mutation (IHC stain, ×400); (C) Diffuse cytoplasmic expression of anti-BRAFV600E (IHC stain, ×400).Abbreviations: H&E, hematoxylin and eosin; IHC, immunohistochemistry.
Mentions: BAP-1 (BCRA1 associated protein-1) protein is an ubiquitin hydrolase that binds to BRCA1 and functions as a tumor suppressor.83 Germline mutations in BAP-1 have been described that predispose affected family members to uveal and cutaneous melanomas and development of melanocytic lesions with distinct clinical and histologic features.84,85 Affected individuals present with multiple (range 5–50 lesions) well-circumscribed dome-shaped papules near the second decade of life.84,85 Histologically, the melanocytic lesions are located predominantly in the dermis and are composed of epithelioid melanocytes with abundant cytoplasm and distinct nucleoli. The lesions demonstrate similar cytologic features seen with Spitz nevi (Figure 7A). Similar lesions develop in the context of somatically acquired BAP-1 loss. IHC analysis with anti-BAP-1 demonstrates loss of nuclear staining in melanocytic lesions with BAP-1 mutations (Figure 7B). Furthermore, a significant proportion of BAP-1 lesions also frequently harbor a BRAFV600E mutation (Figure 7C). The combined features of BRAFV600E expression and loss of BAP-1 constitutes a distinct subset of Spitz nevi analogous to those harboring gains in chromosome 11p together with HRAS mutation.86

Bottom Line: Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease.This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status.The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, Section of Dermatopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

ABSTRACT
Melanoma is a lethal skin disease with a mostly predictable clinical course according to a known constellation of clinical and pathologic features. The distinction of melanoma from benign melanocytic nevus is typically unequivocol; however, there is a subset of tumors known for its diagnostic challenges, development of late metastases, and difficulties in treatment. Several melanocytic tissue biomarkers are available that can facilitate the histopathologic interpretation of melanoma as well as provide insight into the biologic potential and mutational status of this disease. This review describes the clinical application of some of these established and emerging tissue biomarkers available to assess melanocytic differentiation, vascular invasion, mitotic capacity, and mutation status. The selected tissue biomarkers in this review include MiTF, Sox10, D2-40, PHH3, H3KT (anti-H3K79me3T80ph), anti-BRAFV600E, and anti-BAP-1.

No MeSH data available.


Related in: MedlinePlus