Expression of the proliferation and apoptosis-associated CAS protein in benign and malignant cutaneous melanocytic lesions

We have examined the expression of the cellular apoptosis susceptibility pr otein, a nuclear transport factor that plays a role in apoptosis and cell p roliferation, in benign and malignant melanocytic lesions. Tissue samples o f 55 formalin-fixed, paraffin-embedded melanoma (primary n = 32, metastatic n = 23) and of 27 control cases (junctional dermal, compound, Spitz, Reed, blue nevi, balloon-cell nevus, lentigo maligna) were analyzed by immunohis tochemistry with anti-cellular apoptosis susceptibility antibodies. The per centage of cellular apoptosis susceptibility-positive cells as well as the intensity on a four-point scale was evaluated. In normal skin, expression o f cellular apoptosis susceptibility was primarily found in the basal cell l ayer of the epidermis. Benign melanocytic lesions that stained positive for cellular apoptosis susceptibility (13 of 27) showed a homogeneously distri buted staining pattern with a mean of 5 +/- 12% cellular apoptosis suscepti bility positive cells. Five out of 7 lentigo maligna melanoma, 11 out of 12 superficial spreading melanoma and all acrolentiginous (n = 7) and nodular (n = 6) melanoma showed immunoreactivity of medium (++) to high (+++) inte nsity. Vertical growth phases of primary cutaneous melanoma stained stronge r than horizontally growing cell clusters. All metastases (n = 23) stained strongly positive, the staining pattern being inhomogeneous. Cellular apopt osis susceptibility detection in clinical stages according to UICC showed a n increase from 43 +/- 34% cellular apoptosis susceptibility positive cells in stage I, to 53 +/- 26% in stage II, 68 +/- 24% in stage III and 72 +/- 24% in stage TV, respectively, Because the expression of cellular apoptosis susceptibility correlates predominantly with advanced stages of melanoma, staining with anti-cellular apoptosis susceptibility antibodies may be usef ul for diagnosis of melanoma and possibly as an immunohistochemical prognos tic factor in cutaneous melanocytic lesions.