Melanoma clue: ING4 gene offers new direction for therapy

December 1, 2008

Reduced ING4 staining is associated with melanoma thickness, ulceration and poor overall survival, which suggests that restoring the tumor suppressor ING4 is a possible therapeutic direction.

Key Points

Montreal - ING4 is a human gene that plays a role in the pathogenesis of human melanoma. Manipulation of this gene may hold hope for a new direction in melanoma therapy.

According to Gang Li, M.D., Ph.D., a professor in the department of dermatology and skin science at the University of British Columbia/Vancouver Coastal Health and Research Institute in Vancouver, British Columbia, the underlying mechanisms that regulate the progression of melanoma remain poorly understood.

Earlier research has indicated that inhibitor of growth (ING) family tumor suppressors might play an important role in melanoma development.

Dr. Li described ING4, which was first identified in 2003, as a tumor suppressor and noted that it has been shown to reduce colony-forming efficiency, induce p53-dependent apoptosis and arrest cell cycle at a certain phase.

In this study, investigators first evaluated ING4 expression in different stages of human melanocytic lesions using tissue microarray technology and immunohisto-chemistry.

A total of 237 biopsies including 66 dysplastic nevi, 118 primary melanomas and 53 metastatic melanomas were used for tissue microarray construction.

Due to loss of biopsy cores, 50 dysplastic nevi, 101 primary melanomas and 49 metastatic melanomas could be evaluated for ING4 staining.

The biopsies, dating from 1990-98, were obtained from the department of pathology at the Vancouver General Hospital.

Dr. Li and colleagues saw that, unlike the other ING family members, which have reduced nuclear expression but increased cytoplasmic expression in melanoma, reduced ING4 expression was not the result of nuclear-to-cytoplasm shift.

"We clearly see from our research that ING4 was reduced in primary melanoma and metastatic melanoma," Dr. Li tells Dermatology Times.

Reduced staining

They also found reduced ING4 staining is associated with melanoma thickness and ulceration, as well as poor overall survival and disease-specific five-year survival in patients with primary melanoma.

Statistical analysis revealed that ING4, like tumor thickness, is an independent factor for the poor prognosis of patients with primary melanomas.

If a therapy emerges from this discovery in the future, it would likely be tested in more advanced cases of melanoma, for which there is a paucity of effective treatments.

Disclosure: Dr. Li reports no relevant financial disclosures.