Loss of Expression of Protein Kinase A Regulatory Subunit 1α in Pigmented Epithelioid Melanocytoma But Not in Melanoma or Other Melanocytic Lesions

作者：Artur Zembowicz, Stewart M. Knoepp, Thalia Bei, Sotirios Stergiopoulos, Charis Eng, Martín C. Mihm, Constantine A. Stratakis · 发表于：The American Journal of Surgical Pathology · 年份：2007 · DOI：10.1097/pas.0b013e318057faa7 · 被引用次数：132 · 研究领域：Cardiac tumors and thrombi、Vascular Tumors and Angiosarcomas、Cutaneous Melanoma Detection and Management

Pigmented epithelioid melanocytoma (PEM) is a recently described entity comprising most cases previously described as "animal-type melanoma" and epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory subunit type 1alpha (R1alpha) (coded by the PRKAR1A gene) are found in more than half of CNC patients. In this study, we investigated whether PEM and EBN are related at the molecular level, and whether changes in the PRKAR1A gene status and the expression of the R1alpha protein may be involved in the pathogenesis of PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin-stained sections and immunohistochemistry (IHC) with R1alpha antibody were performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86 melanomas of various types); in addition, 170 tissue microarray sections consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas, and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on preexisting pathologic reports and were confirmed for this study. DNA studies [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene sequencing] were performed ...