The usefulness of c-Kit in the immunohistochemical assessment of melanocytic lesions

Abstract

C-Kit (CD117), the receptor for the stem cell factor, a growth factor for melanocyte migration and proliferation, has shown differential immunostaining in various benign and malignant melanocytic lesions. The purpose of this study is to compare c-Kit immunostaining in benign nevi and in primary and metastatic malignant melanomas, to determine whether c-Kit can aid in the differential diagnosis of these lesions. c-Kit immunostaining was performed in 60 cases of pigmented lesions, including 39 benign nevi (5 blue nevi, 5 intra-dermal nevi, 3 junctional nevi, 15 cases of primary compound nevus, 11 cases of Spitz nevus), 18 cases of primary malignant melanoma and 3 cases of metastatic melanoma. The vast majority of nevi and melanomas examined in this study were positive for c-Kit, with minimal differences between benign and malignant lesions. C-Kit cytoplasmatic immunoreactivity in the intraepidermal proliferating nevus cells, was detected in benign pigmented lesions as well as in malignant melanoma, increasing with the age of patients (P=0.007) in both groups. The patient’s age at presentation appeared to be the variable able to cluster benign and malignant pigmented lesions. The percentage of c-Kit positive intraepidermal nevus cells was better associated with age despite other variables (P=0.014). The intensity and percentage of c-Kit positivity in the proliferating nevus cells in the dermis was significantly increased in malignant melanocytic lesions (P=0.015 and P=0.008) compared to benign lesions (compound melanocytic nevi, Spitz nevi, intradermal nevi, blue nevi). Immunostaning for c-Kit in metastatic melanomas was negative. Interestingly in two cases of melanoma occurring on a pre-existent nevus, the melanoma tumor cells showed strong cytoplasmatic and membranous positivity for c-kit, in contrast with the absence of any immunoreactivity in pre-existent intradermal nevus cells. C-Kit does not appear to be a strong immunohistochemical marker for distinguishing melanoma from melanocytic nevi, if we consider c-Kit expression in intraepidermal proliferating cells. The c-Kit expression in proliferating melanocytes in the dermis could help in the differential diagnosis between a superficial spreading melanoma (with dermis invasion) and a compound nevus or an intradermal nevus. Finally, c-Kit could be a good diagnostic tool for distinguishing benign compound nevi from malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma.

Immunohistochemical expression of CD117 and CD34 as stem cell markers in intradermal nevi, dysplastic nevi, and malignant melanomas

“…There was no significant difference between dysplastic nevi and MM in the expression of CD117 (P-value = 0.193). Pilloni et al [11], in their study on melanocytic lesions including blue nevi, intradermal nevi, junctional nevi, compound nevi, Spitz nevi, and MMs, found that the vast majority of nevi and melanomas were positive for CD117 with minimal difference between benign and malignant lesions; however, the percentage of CD117-positive intradermal nevus cells was significantly increased in MM compared with benign lesions. [20].…”

“…The CD117/stem cell factor interaction is critical for the survival and development of stem cells involved in hematopoiesis [8], pancreas development [9], and melanogenesis [10]. CD117 is a growth factor for melanocyte migration and proliferation [11]. Malignant transformation of melanocytes is associated with changes in the expression of the CD117 receptor [12].…”

Resveratrol Inhibits Alpha-Melanocyte-Stimulating Hormone Signaling, Viability, and Invasiveness in Melanoma Cells

“…β -catenin, an important intermediate in Wnt signaling pathway, has been identified as a key point for melanocyte development [26]. c-Kit (CD117), the receptor for the stem cell factor (SCFR), is a growth factor for melanocyte migration and proliferation and has been shown differential expression in various malignant melanocytic lesions with dermis invasion and to differentiate metastatic melanoma from primary melanoma [27]. Additionally, α -MSH is a physiological ligand that binds to melanocortin-1 receptor, initiates signal transduction to induce transcription factor MITF expression, and then leads to increase in melanin synthesis [5].…”

Immunohistochemical Expression of c-kit Receptor (CD117) in Two Pigmentary Disorders

“…The c-kit/SCF interaction is critical for the survival and development of stem cells involved in hematopoiesis in pancreas development and in melanogenesis [3][4][5]. CD117 is a growth factor for melanocyte survival, migration and proliferation [6].…”