Id2 Expression in Cutaneous Nevi and Melanomas
H Froehlich, J Brennick, H Xie, M Israel, S Yan. Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Norris Cotton Cancer Center, Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, NH
Background: Inhibitors of DNA binding (Id) proteins are helix-loop-helix (HLH) transcription factors lacking a basic DNA binding domain and hence act as dominant negative factors blocking basic HLH proteins from binding DNA. One member of the Id family, Id2, has been recognized to be overexpressed in some tumors and yet may act as a tumor suppressor in mice. Recently, a role for Id2 in the pathogenesis of melanoma has been proposed because of its decreased expression in an aggressive form of uveal melanoma. This study aims to explore the expression of Id2 in cutaneous benign and malignant melanocytic lesions.
Design: Immunohistochemical staining for Id2 was performed on a tissue microarray of 88 primary malignant melanomas, 20 metastatic malignant melanomas, and 52 benign nevi. Nuclear and cytoplasmic expression of Id2 was scored as a dichotomous variable with "1" defined as no or low expression and "2" defined as moderate to high expression. Data was evaluated and analyzed by Fisher's exact tests and logistic regression.
Results: High nuclear Id2 expression was detected in 96% of benign nevi and 67% of all melanomas (p<0.01). The proportion of cases with high nuclear Id2 expression is 72% in primary melanomas and 45% in metastatic melanomas (p<0.05). There was also a significant difference in Id2 nuclear expression between the primary melanoma (72%) and the benign nevus (96%) groups (p<0.01). Cytoplasmic expression of Id2 was scored as high in 62% of melanoma versus 40% in benign nevi (p<0.01). Three risk factors including melanoma tumor thickness, mitotic rate, and presence of ulceration were significantly related to lower nuclear Id2 expression level. No significant association was found between these factors and cytoplasmic Id2 expression.
Conclusions: Nuclear Id2 expression significantly decreases from benign nevi to primary melanomas and metastatic melanomas. In addition, decreased nuclear Id2 expression seems to correlate with tumor progression demonstrated by the inverse correlation of nuclear expression of Id2 with tumor thickness, mitotic rate, and the presence of ulceration. Loss of nuclear Id2 expression may play an important role in cutaneous melanoma tumorigenesis.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 84, Wednesday Afternoon