[513] Immunohistochemical Expression of GSK-3β and CDC25A in Cutaneous Lymphomas.

Maria Pletneva, Megan S Lim, Dafydd G Thomas, Linglei Ma. University of Michigan Medical Center, Ann Arbor

Background: Tyrosine phosphatase Cdc25A is required for G1 to S progression in cell cycle. GSK-3β, a serine/threonine kinase, regulates cell cycle by phosphorylating key proteins and targets Cdc25A for proteolysis. GSK-3β inactivation correlated strongly with Cdc25A accumulation in human tumors. Inhibitors of both enzymes are attractive targets for anticancer therapy development. Here we evaluated the expression of Cdc25A and p-GSK-3β (phosphorylated inactivated form) in cutaneous lymphomas.
Design: Tissue microarray (TMA) was created using material obtained at our Pathology Department. Diagnoses included systemic and cutaneous anaplastic large cell lymphoma (ALCL), lymphomatoid papulosis (LyP), mycosis fungoides (MF), MF with large cell transformation (MF-LCT), primary cutaneous B-cell lymphomas (BL), systemic BL with secondary cutaneous involvement, and cutaneous lymphoid hyperplasia (LH). Cdc25A and p-GSK-3β immunohistochemical staining of TMA was evaluated for immunoreactive lesional cells and scored negative/low (<20% of positive cells) or high (≥20% of positive cells).
Results: P-GSK-3β immunoreactivity was cytoplasmic and strong in all lymphoma types (Table). Staining for Cdc25A was mostly cytoplasmic with some perinuclear accentuation. No or low levels of Cdc25A were observed in most cutaneous ALCLs, LyPs, cutaneous and systemic BLs with secondary cutaneous involvement. In contrast, high levels of Cdc25A were noted in some MFs and aggressive lymphomas, such as systemic ALCL, MF-LCT, and a case of primary cutaneous diffuse large B-cell lymphoma of leg type. Interestingly, p-GSK-3β was overexpressed in cutaneous LH, while Cdc25A was negative or low.

GSK-3β and Cdc25A expression in lymphoma TMA
 GSK3βCdc25A
 neg/lowhighneg/lowhigh
systemic ALCL25%75%50%50%
cutaneous ALCL14%86%86%14%
LyP14%86%86%14%
MF0%100%44%56%
MF-LCT11%89%33%67%
cutaneous BL0%100%82%18%
systemic BL0%100%100%0%
cutaneous LH0%100%100%0%



Conclusions: The differential expression of Cdc25A suggests that p-GSK-3β and Cdc25A axis may play a role in some aggressive forms of cutaneous lymphomas. The discordant expression of Cdc25 and p-GSK-3β indicates that non-Cdc25A cell cycle pathways may be involved in indolent skin lymphomas such as cutaneous ALCL. Our findings may be useful for directing future specific inhibitor therapy, however, larger studies are necessary to establish the role of p-GSK-3β and Cdc25A in these lesions.
Category: Dermatopathology

Wednesday, March 2, 2011 1:00 PM

Poster Session VI # 108, Wednesday Afternoon

 

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