Nuclear ING2 expression is reduced in human cutaneous melanomas

Abstract

Cutaneous malignant melanoma is a severe and sometimes life-threatening cancer. The molecular mechanism of melanomagenesis is incompletely understood. Deregulation of apoptosis is probably one of the key factors contributing to the progression of melanoma. The inhibitor of growth (ING) family proteins are candidate tumour suppressors which play important roles in apoptosis. Downregulated expression of ING proteins have been reported in several tumour types, including the loss of nuclear expression of p33ING1b in melanoma. As ING2 exhibits 58.9% homology with p33ING1b, we hypothesized that the aberrant expression of ING2 may be involved in melanomagenesis. Here, we used tissue microarray technology and immunohistochemistry to examine ING2 expression in human nevi and melanoma biopsies. Our data showed that nuclear ING2 expression was significantly reduced in radial growth phase (RGP), vertical growth phase (VGP), and metastatic melanomas compared with dysplastic nevi (P < 0.05). Our data also revealed that nuclear ING2 expression was not associated with patient's gender, age or tumour thickness, ulceration, American Joint Committee on Cancer (AJCC) stage, tumour subtype, location and 5-year survival (P > 0.05). Taken together, our results suggest that nuclear ING2 expression is significantly reduced in human melanomas and that reduced ING2 may be an important molecular event in the initiation of melanoma development.

Figure 1

Representative images of ING2 immunohistochemical staining in human melanocytic lesions. Strong ING2 expression in adjacent normal epidermis (A), normal nevi (B), dysplastic nevi (C), and weak ING2 staining in primary melanoma (D) and metastatic melanoma (E). Arrows indicate strong staining in melanocyte. Magnification, × 400.

Figure 2

ING2 nuclear expression at different stages of melanocytic lesions. There are less ING2 nuclear expression in RGP, VGP and metastatic melanomas compared with dysplastic nevi (P=0.029, 0.0001 and 0.0286, respectively, Mann–Whitney test).

Figure 3

No correlation was found between ING2 nuclear expression and tumour thickness (P>0.05, Kruskal–Wallis test) (A) and tumour ulceration (P>0.05, Mann–Whitney test) (B) of primary melanomas, or AJCC stages for all 122 melanoma cases (P>0.05, Kruskal–Wallis test) (C).

Figure 4

ING2 nuclear expression and 5-year patient survival. ING2 nuclear expression is not correlated with 5-year overall (A, C) and disease-specific survival (B, D) in primary melanoma patients (A, B) or metastatic melanoma patients (C, D).