Diagnostic Utility of IMP3 in Segregating Metastatic Malignant Melanomas from Benign Nevi in Lymph Nodes
MJ Mentrikoski, L Ma, JG Pryor, LA McMahon, BO Spaulding, GA Scott, HL Wang, H Xu. University of Rochester Medical Center, Rochester; University of Michigan Medical Center, Ann Arbor; Dako North America, Carpinteria; Cedars-Sinai Medical Center, Los Angeles
Background: Benign melanocytic nevi are encountered within the capsule and trabeculae of lymph nodes. These benign nevi may create diagnostic problems when found within sentinel lymph nodes of patients with cutaneous melanoma. It has previously been shown that insulin-like growth factor-II messenger RNA (mRNA)-binding protein 3 (IMP3), also known as K homology domain-containing protein overexpressed in cancer (KOC) and L523S, has diagnostic value in distinguishing cutaneous melanoma from benign nevi, and that IMP3 is a progression biomarker of malignant melanoma. The aim of this study was to determine if detection of IMP3 expression can be used to segregate metastatic melanoma from benign nevi in sentinel lymph nodes.
Design: Using monoclonal antibodies against IMP3 and Melan-A, 24 sentinel and 5 non-sentinel lymph nodes from 28 patients with metastatic malignant melanoma and 10 sentinel lymph nodes with benign nevi from 9 patients with cutaneous malignant melanoma were examined. Benign nevi were located both in the capsule (n=8) and trabeculae (n=2). Nevic cells were highlighted on Melan-A stained slides, and a diagnosis of melanoma was based on cytologic atypia and comparison with the primary melanomas. Care was taken so that cells positive for Melan-A were the same cells examined when evaluating for IMP3 expression. IMP3 is known to be expressed in lymph node germinal centers, and this was also taken into account. A case was considered positive if more than 10% of the cells of interest showed cytoplasmic IMP3 staining. The staining intensity was graded as weak, moderate, and strong.
Results: Twenty of 29 (69%) sentinel and non-sentinel lymph nodes with metastatic melanoma were immunohistochemically positive for IMP3 with more than 10% of tumor cells stained. The staining intensity was variable from weak to strong. No IMP3 expression was detected in any of benign nodal nevi, while they were highlighted on Melan-A staining. Benign germinal centers were highlighted with IMP3 staining in all cases, which were used as internal positive controls.
Conclusions: A large proportion of nodal metastatic melanomas express IMP3, but benign nodal nevi do not. These findings indicate that IMP3 is a valuable diagnostic biomarker in distinguishing benign nevi from metastatic melanomas in lymph nodes.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 79, Monday Morning