[1712] Expression of c-KIT by Cell Morphology in Uveal Melanomas

P Tranchida, H Budev, S Sethi, H Jaratli, W Sakr, T Giorgadze. Wayne State University, Detroit, MI

Background: Uveal melanoma (UM) is the most common primary intraocular cancer in adults. The overall prognosis is unfavorable, with 40-50% of patients developing metastases within 10 years of diagnosis. Recent reports showed that tyrosine kinase inhibitors (TKI) reduce growth in UM-derived cell lines and may be useful in treatment of patients with UM. However, data regarding c-KIT (tyrosine kinase receptor) expression in UM are rare and inconsistent. Our objective was to determine c-KIT immunohistochemical (IHC) expression in UM and correlate the staining patterns with tumor cell types according to modified Callender's classification.
Design: 21 consecutive UM cases treated by enucleation were retrieved (9 females, 12 males; age range: 33-83 years). Immunostaining for c-KIT was performed in representative tissue sections. The staining (cytoplasmic or membranous) was evaluated as negative (<10%), weak (10-50%), or strong (>50%).
Results: The table shows that c-KIT immunoreactivity correlated strongly with the cellular composition of UM. Strong IHC staining was prevalent in spindle cells (both A and B types) and in the spindle cell component of the mixed spindle and epithelioid morphology. Negative or weak IHC expression was evident in all cases of epithelioid UM and the epithelioid component of tumors with mixed morphology. Furthermore, c-KIT staining helped unveil areas with epithelioid morphology in the original H&E sections.

Results of c-KIT immunostaining

Case number	Tumor composition	c-KIT staining (spindle cell)	c-KIT staining (epithelioid)
1	mixed (SB>E)	strong	negative
2	SB	strong	NA
3	SB>SA	strong	NA
4	mixed (SB>SA>E)	strong	negative
5	SA>SB	strong	NA
6	SB	weak	NA
7	mixed (E>SB)	weak	weak
8	SB>SA	strong	NA
9	mixed (E>SB)	strong	negative
10	mixed (E>SB)	weak	negative
11	SB>SA	strong	NA
12	SB	strong	NA
13	mixed (SB>E)	strong	negative
14	SB	strong	NA
15	SB>SA	strong	NA
16	SB	strong	NA
17	mixed (SB>E)	strong	negative
18	SB	negative	NA
19	SB	strong	NA
20	SB	strong	NA
21	E	NA	negative

KEY: E=epithelioid, SA=spindle A, SB=spindle B, NA=Not applicable


Conclusions: Our results show that c-KIT immunoexpression is prevalent in spindle cell UM to the exclusion of purely or predominantly epithelioid tumors. These observations may provide a rationale for considering targeting therapy with TKI only in patients with UM of pure spindle cell type or mixed UM with predominance of spindle cells.
Category: Ophthalmic

Wednesday, March 24, 2010 1:00 PM

Poster Session VI # 257, Wednesday Afternoon