Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma.

Agnieszka Witkiewicz, Puthiyaveettil Raghunath, Agnieszka Wasik, Jacqueline M. Junkins-Hopkins, Dan Jones, Qian Zhang, Niels Odum, Mariusz A. Wasik

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

Cutaneous T-cell lymphoma (CTCL) comprises distinct and often progressive stages of skin involvement by patches, plaques, and tumors. We have previously demonstrated that CTCL-derived malignant T-cell lines display loss of a tumor suppressor SHP-1 tyrosine phosphatase because of epigenetic silencing of its gene. The silencing is induced by an activated phosphorylated (p)-STAT3 transcription factor in cooperation with DNA methyltransferase 1 (DNMT1), the key member of the epigenetic gene silencing machinery. To determine at which stage of CTCL the loss of SHP-1 occurs and how it correlates with the expression of (p)-STAT3 and DNMT1, we examined by immunohistochemistry 47 formalin-fixed skin biopsies from various stages of CTCL. Six pairs of the biopsies were obtained before and after CTCL progression at the patch or plaque and tumor stage, respectively. In 5 of these pairs, we identified loss of SHP-1 expression in atypical lymphocytes at the tumor stage; less prominent SHP-1 loss was noted in 3 biopsies from the earlier stage. The SHP-1 loss was also observed in 5 of 6 tumor, 12 of 18 plaque, and only 2 of 11 patch stages in patients with single biopsies. The expression of (p)-STAT3 and DNMT1 could be identified in almost all cases in at least a subset of the lesional cells. Based on these findings, we postulate that expression of (p)-STAT3 and DNMT1 occurs at the early stages of CTCL, and that this expression alone seems insufficient to induce loss of SHP-1 expression. In turn, SHP-1 loss correlates with, and may contribute to, progression of CTCL.

Original languageEnglish (US)
Pages (from-to)462-467
Number of pages6
JournalHuman Pathology
Volume38
Issue number3
DOIs
StatePublished - Mar 1 2007

Keywords

  • Cutaneous T-cell lymphoma
  • DNMT1 DNA methyltransferase
  • SHP-1 tyrosine phosphatase
  • STAT3 transcription factor

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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  • Cite this

    Witkiewicz, A., Raghunath, P., Wasik, A., Junkins-Hopkins, J. M., Jones, D., Zhang, Q., Odum, N., & Wasik, M. A. (2007). Loss of SHP-1 tyrosine phosphatase expression correlates with the advanced stages of cutaneous T-cell lymphoma. Human Pathology, 38(3), 462-467. https://doi.org/10.1016/j.humpath.2006.09.012