Sparrow L E, Eldon M J, English D R, Heenan P J
Department of Pathology, University of Western Australia, Queen Elizabeth II Medical Centre, Nedlands.
Am J Dermatopathol. 1998 Jun;20(3):255-61. doi: 10.1097/00000372-199806000-00006.
To determine whether variation in the level of expression of p16 and p21WAF1 (p21) is associated with critical stages in cutaneous melanoma development or progression, the expression of these antigens was analyzed by immunohistochemistry in 110 benign and malignant melanocytic lesions. Differential expression of p16 protein has been reported in cutaneous melanocytic lesions, with loss of expression associated with the invasive stage of tumor development. Expression of p16 was seen in 31 of 35 benign melanocytic tumors (89%), 11 of 12 in situ melanomas (92%), 19 of 38 invasive primary melanomas (50%), and 16 of 25 metastatic melanomas (64%). There was a significant difference in the expression level of p16 observed in in situ versus invasive primary melanomas (p = 0.006), which is consistent with loss of normal p16 activity occurring in association with malignant tumor invasion. Overall, p21 levels were found to be low or undetectable in the majority of benign lesions, with greater p21 expression seen in malignant tumors. p21 was expressed in 28% of nevi, 60% of in situ melanomas, 61% of invasive melanomas, and 48% of metastatic melanomas. Among primary invasive tumors, the frequency of p21 expression increased with level of invasion (p < 0.01) and with increasing thickness (p < 0.01). However, differences in p21 expression were not clearly related to a particular stage of melanoma development.
为了确定p16和p21WAF1（p21）表达水平的变化是否与皮肤黑色素瘤发生或进展的关键阶段相关，通过免疫组织化学分析了110例良性和恶性黑素细胞性病变中这些抗原的表达。皮肤黑素细胞性病变中已报道p16蛋白存在差异表达，其表达缺失与肿瘤发展的侵袭阶段相关。在35例良性黑素细胞瘤中有31例（89%）可见p16表达，12例原位黑色素瘤中有11例（92%），38例侵袭性原发性黑色素瘤中有19例（50%），25例转移性黑色素瘤中有16例（64%）。原位黑色素瘤与侵袭性原发性黑色素瘤中观察到的p16表达水平存在显著差异（p = 0.006），这与恶性肿瘤侵袭时正常p16活性丧失一致。总体而言，在大多数良性病变中发现p21水平较低或无法检测到，在恶性肿瘤中p21表达更高。p21在28%的痣、60%的原位黑色素瘤、61%的侵袭性黑色素瘤和48%的转移性黑色素瘤中表达。在原发性侵袭性肿瘤中，p21表达频率随侵袭程度增加（p < 0.01）和厚度增加（p < 0.01）而增加。然而，p21表达的差异与黑色素瘤发展的特定阶段并无明显关联。
