The Expression of mTOR Pathway Proteins in Cutaneous Lymphomas
L Ma, PN Bogner, S Tripp, SL Perkin, D Abbott, M Lim. University of Michigan, Ann Arbor, MI; University of Utah, Salt Lake City, UT; Ohio State University, Columbus, OH
Background: Mammalian target of rapamycin (mTOR) is a protein kinase that regulates cell growth. The translation regulators p70S6 kinase (p70) and pS6 ribosomal protein (pS6) are well characterized downstream effectors of the mTOR pathway. Previous studies showed that mTOR pathway proteins are up-regulated in some systemic anaplastic large cell lymphomas (ALCL) and systemic B-cell lymphomas. In this study, we examined the expression of mTOR pathway proteins in primary cutaneous lymphomas.
Design: Using tissue microarrays, immunostaining of mTOR pathway proteins (phospho-mTOR, phospho-p70 and phospho-pS6) was performed on a total of 74 lymphoid lesions, including 6 cutaneous lymphoid hyperplasias, 7 cutaneous ALCLs, 4 systemic ALCLs, 11 mycosis fungoides (MF), 15 lymphomatoid papulosis (LyP), 10 MF with large cell transformation (MF-LCT), 11 primary cutaneous B-cell lymphomas (PCBCL) and 10 systemic B-cell lymphomas with secondary skin involvement (SBCL). A marker was considered positive if >10% of lesional cells showed nuclear and/or cytoplasmic staining.
Results: In cutaneous lymphoid hyperplasia, p70 and pS6 stained reactive B-cells, while mTOR was negative. Subsets of systemic and cutaneous ALCL stained positive for mTOR (weak), p70 and pS6 (moderate to strong). mTOR, p70 and pS6 reactivity was detected in some cases of LyP, MF, and MF-LCT. For cutaneous B-cell lymphomas, both PCBCL and SBCL expressed mTOR, p70 and pS6 at comparable levels. Results are summarized in Table 1.
|Systemic ALCL||4||2/4 (50%)||3/4 (75%)||1/4 (25%)|
|Cutaneous ALCL||7||1/7 (14%)||3/7 (43%)||2/7 (29%)|
|LyP||15||5/15 (33%)||4/15 (27%)||8/15 (53%)|
|MF||11||5/11 (45%)||2/11 (18%)||4/11 (36%)|
|MF-LCT||10||4/10 (40%)||4/10 (40%)||6/10 (60%)|
|Cutaneous lymphoid hyperplasia||6||0/6 (0%)||3/6 (50%)||4/6 (67%)|
|Cutaneous. B-cell lymphoma||11||6/11 (55%)||4/11 (36%)||5/11 (45%)|
|Systemic B-cell lymphoma||10||6/10 (60%)||4/10 (40%)||2/10 (20%)|
Conclusions: 1. Compared to benign cutaneous lymphoid hyperplasias, mTOR levels are elevated in primary cutaneous T-cell lymphoproliferative disorders and mTOR pathway proteins are upregulated in PCBCL and SBCL. 2. p70 and pS6 are activated in MF-LCT, probably through upstream proteins other than mTOR. 3. The activation of mTOR pathway proteins in cutaneous lymphoma suggests potential for Rapamycin as a therapeutic agent.
Tuesday, March 10, 2009 1:00 PM
Poster Session IV # 58, Tuesday Afternoon