Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas.
Merkel cell carcinoma is an uncommon and aggressive primary cutaneous neuroendocrine carcinoma with a high rate of recurrence and metastasis. Optimal management is controversial; consequently, it is imperative to identify the signaling pathways involved in the pathogenesis of Merkel cell carcinoma so that effective therapeutic targeting agents can be developed. We previously reported that K homology domain-containing protein overexpressed in cancer is expressed in high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. The K homology domain-containing protein overexpressed in cancer (KOC), also known as L523S and IMP-3, is an insulin-like growth factor II messenger RNA-binding protein that promotes tumor cell proliferation by enhancing insulin-like growth factor II protein expression. Expression of KOC in Merkel cell carcinoma has not been investigated. We studied 20 Merkel cell carcinomas by immunohistochemistry using a monoclonal antibody against L523S/KOC. Of 20 Merkel cell carcinomas, 18 (90%) overexpressed KOC, with 11 (55%) overexpressing KOC in greater than 90% of tumor cells, 3 (15%) overexpressing KOC in 50% to 90% of tumor cells, 3 (15%) overexpressing KOC in 10% to 50% of tumor cells, and 1 (5%) overexpressing KOC in less than 10% of tumor cells. The immunostaining intensity was variable, with moderate to strong staining in 14 cases and weak staining in the remaining 4. Extent of expression of K homology domain-containing protein overexpressed in cancer predicted metastasis (P = .04) and was weakly correlated with increased tumor size (P = .08). In conclusion, Merkel cell carcinoma expresses K homology domain-containing protein overexpressed in cancer with an expression pattern similar to high-grade neuroendocrine carcinomas of the lung and extrapulmonary small cell carcinomas. We propose K homology domain-containing protein overexpressed in cancer as a potential target molecule for the treatment of high-grade neuroendocrine carcinomas, irrespective of anatomical location, and a potential marker to predict metastatic disease.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Jennifer G
JG
Pryor
Rochelle A
RA
Simon
Patricia A
PA
Bourne
Betsy O
BO
Spaulding
Glynis A
GA
Scott
Haodong
H
Xu
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015266:Carcinoma, Merkel Cell / Q000378:metabolism* / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; C498780:IGF2BP3 protein, human; D009363:Neoplasm Proteins; D016601:RNA-Binding Proteins