Ann Dermatol.  2016 Oct;28(5):548-554. 10.5021/ad.2016.28.5.548.

Expression of Phosphatase and Tensin Homologue, phospho-Akt, and p53 in Acral Benign and Malignant Melanocytic Neoplasms (Benign Nevi, Dysplastic Nevi, and Acral Melanomas)

• Lyu SM
• Wu JY
• Byun JY
• Choi HY
• Park SH
• Choi YW

• KMID: 2382877
• DOI: http://doi.org/10.5021/ad.2016.28.5.548

Abstract

BACKGROUND
The role of the phosphatidylinositol-3 kinase signaling pathway in the development of acral melanoma has recently gained evidence. Phosphatase and tensin homologue (PTEN), one of the key molecules in the pathway, acts as a tumor suppressor through either an Akt-dependent or Akt-independent pathway. Akt accelerates degradation of p53.
OBJECTIVE
We assessed the expression of PTEN, phospho-Akt (p-Akt), and p53 by immunohistochemistry in benign acral nevi, acral dysplastic nevi, and acral melanomas in the radial growth phase and with a vertical growth component.
METHODS
Ten specimens in each group were included. Paraffin-embedded specimens were immunostained with antibodies for PTEN, p-Akt, and p53. We scored both the staining intensity and the proportion of positive cells. The final score was calculated by multiplying the intensity score by the proportion score.
RESULTS
All specimens of benign acral nevi except one showed some degree of PTEN-negative cells. The numbers of p-Akt and p53-positive cells were higher in acral dysplastic nevi and melanoma than in benign nevi. P-Akt scores were 1.7, 1.8, 2.6, and 4.4, and p53 scores were 2.0, 2.1, 3.8, and 4.1 in each group. PTEN and p-Akt scores in advanced acral melanoma were higher than in the other neoplasms.
CONCLUSION
The expression of PTEN was decreased and the expression of p-Akt was increased in acral melanoma, especially in advanced cases. The PTEN-induced pathway appears to affect the late stage of melanomagenesis. Altered expression of p-Akt is thought to be due to secondary changes following the loss of PTEN.

Keyword

Acral; Akt; Melanocytic; p53; PTEN

MeSH Terms

Antibodies
Dysplastic Nevus Syndrome*
Immunohistochemistry
Melanoma
Nevus*
Phosphotransferases
Antibodies
Phosphotransferases

Figure

• 

  Fig. 1 Comparison of the final staining scores between acral melanocytic lesions. (A) Phosphatase and tensin homologue (PTEN) (PTEN loss score), (B) phospho-Akt (p-Akt), (C) p53. a: benign acral nevi group, b: acral dysplastic nevi group, c: acral melanoma group in radial growth phase, d: acral melanoma group with a vertical growth. p<0.05.

• 

  Fig. 2 Representative figures of immunohistochemical staining for phosphatase and tensin homologue (PTEN) (B, F, J, N: ×400), phospho-Akt (p-Akt) (C, G, K, O, ×400), and p53 protein (D, H, L, P, ×400) in benign acral nevus (A~D), acral dysplastic nevus (E~H), acral melanoma in radial growth phase (I~L), acral melanoma with vertical growth (M~P). Patchy loss of nuclear PTEN is remarkable in advanced acral melanoma specimen (J, arrows: nuclear PTEN-lost cells). A nest of cytoplasmic p-Akt-positive tumor cells are noted in advanced acral melanoma. Both staining intensity and proportion of the p53-positive cells are higher in acral melanoma than two benign nevi groups. A, E, I, and M were stained with H&E (×100). Arrows: F, nuclear PTEN-lost cells; H, p53-positive cells; K, p-Akt-positive cells.

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