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Tyrosine phosphatase SHP-1 is expressed higher in multisystem than in single-system Langerhans cell histiocytosis by immunohistochemistry

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Abstract

Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cell (LC)-like CD1a-positive cell (LCH cell) with unknown causes. LCH consists of two subtypes: single-system LCH (LCH-SS) with favorable prognosis and multisystem LCH (LCH-MS) with poor prognosis. LCH has been indicated as a neoplastic disorder from monoclonal characteristics of LCH cells. This study aimed to investigate an expression of tyrosine phosphatase SHP-1 in LCH, since its expression levels were variously reported in many tumors, overexpression in ovarian cancers (a candidate oncoprotein), and downregulation by methylation in gastric cancers, prostate cancers, malignant lymphomas, and leukemias (a putative tumor suppressor). By immunohistochemistry (IHC), the SHP-1 expression in LCs and LCH cells was compared in LCH (two subtypes: LCH-SS = 21, LCH-MS = 12), dermatopathic lymphadenopathy (DLA) (n = 9) and normal epidermal LCs (n = 3) near LCH lesion. IHC results were analyzed semiquantitatively using a Photoshop software. The mean intensity score (IS) of DLA, LCH-SS, LCH-MS, and LCs were 47, 100, 139, and 167 (in arbitrary unit), respectively. The IS had significant differences among LCH-SS, LCH-MS, and DLA (p < 0.01). SHP-1 is expressed significantly higher in LCH-MS than in LCH-SS. SHP-1 can be a progression marker of LCH. SHP-1 is also useful for differential diagnosis between LCH in lymph nodes and DLA.

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Abbreviations

B-ALL:

B lymphoblastic leukemia

CMYK:

Cyan/magenta/yellow/key

IF:

Immunofluorescence

IHC:

Immunohistochemistry

IS:

Intensity score

ISs:

Intensity scores

LC:

Langerhans cell

LCH:

Langerhans cell histiocytosis

LCH cell:

Langerhans cell-like CD1a-positive cell

LCH-MS:

Multisystem LCH

LCH-SS:

Single-system LCH

LCS:

LC sarcoma

meV:

Viable motheaten mice

MHC:

Major histocompatibility complex

PTPN6:

Tyrosine–protein phosphatase nonreceptor type 6

SHP-1:

Src homology region 2 domain-containing phosphatase 1

SHPS-1:

Substrate of SHP-1

T-ALL:

T lymphoblastic leukemia

References

  1. Aiba S, Katz S (1990) Phenotypic and functional characteristics of in vivo activated Langerhans cells. J Immunol 145:2791–2796

    PubMed  CAS  Google Scholar 

  2. Fukunaga A, Nagai H, Yu X et al (2006) Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation. Eur J Immunol 36:3216–3226

    Article  PubMed  CAS  Google Scholar 

  3. Willman CL, Busquet L, Griffith BB et al (1994) Langerhans’-cell histiocytosis (histiocytosis X): a clonal proliferative disease. N Engl J Med 331:154–160

    Article  PubMed  CAS  Google Scholar 

  4. Yu RC, Chu C, Buluwela L, Chu AC (1994) Clonal proliferation of Langerhans cells in Langerhans cell histiocytosis. Lancet 343:767–768

    Article  PubMed  CAS  Google Scholar 

  5. Feldman AL, Berthold F, Arceci RJ et al (2005) Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis. Lancet Oncol 6:435–437

    Article  PubMed  Google Scholar 

  6. Magni M, Di Nicola M, Carlo-Stella C et al (2002) Identical rearrangement of immunoglobulin heavy chain gene in neoplastic Langerhans cells and B-lymphocytes: evidence for a common precursor. Leuk Res 26:1131–1133

    Article  PubMed  CAS  Google Scholar 

  7. Coury F, Annels N, Rivollier A et al (2008) Langerhans cell histiocytosis reveals a new IL-17A-dependent pathway of dendritic cell fusion. Nat Med 14:81–87

    Article  PubMed  CAS  Google Scholar 

  8. Allen CE, McClain KL (2009) Interleukin-17A is not expressed by CD207(+) cells in Langerhans cell histiocytosis lesions. Nat Med 15:483–484

    Article  PubMed  CAS  Google Scholar 

  9. Badalian-Very G, Vergilio JA, Degar BA et al (2010) Recurrent BRAF mutations in Langerhans cell histiocytosis. Blood 116:1919–1923

    Article  PubMed  CAS  Google Scholar 

  10. Zhang Q, Raghunath PN, Vonderheid E, Odum N, Wasik MA (2000) Lack of phosphotyrosine phosphatase SHP-1 expression in malignant T-cell lymphoma cells results from methylation of the SHP-1 promoter. Am J Pathol 157:1137–1146

    Article  PubMed  CAS  Google Scholar 

  11. Oka T, Yoshino T, Hayashi K et al (2001) Reduction of hematopoietic cell specific tyrosine phosphatase SHP-1 gene expression in natural killer cell lymphoma and various types of lymphomas/leukemias: combination analysis with cDNA expression array and tissue microarray. Am J Pathol 159:1495–1505

    Article  PubMed  CAS  Google Scholar 

  12. Mok SC, Kwok TT, Berkowitz RS, Barrett AJ, Tsui FW (1995) Overexpression of the protein tyrosine phosphatase, non-receptor type 6 (PTPN6), in human epithelial ovarian cancer. Gynecol Oncol 57:299–303

    Article  PubMed  CAS  Google Scholar 

  13. Julien SG, Dubé N, Hardy S, Tremblay ML (2011) Inside the human cancer tyrosine phosphatome. Nat Rev Cancer 11:35–49

    Article  PubMed  CAS  Google Scholar 

  14. Su L, Zhao Z, Bouchard P et al (1996) Positive effect of overexpressed protein-tyrosine phosphatase PTP1C on mitogen-activated signaling in 293 cells. J Biol Chem 271:10385–10390

    Article  PubMed  CAS  Google Scholar 

  15. You M, Zhao Z (1997) Positive effects of SH2 domain-containing tyrosine phosphatase SHP-1 on epidermal growth factor- and interferon-gamma-stimulated activation of STAT transcription factors in HeLa cells. J Biol Chem 272:23376–23381

    Article  PubMed  CAS  Google Scholar 

  16. Geissmann F, Lepelletier Y, Fraitag S et al (2001) Differentiation of Langerhans cells in Langerhans cell histiocytosis. Blood 97:1241–1248

    Article  PubMed  CAS  Google Scholar 

  17. Fukunaga A, Nagai H, Noguchi T et al (2004) Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 regulates the migration of Langerhans cells from the epidermis to draining lymph nodes. J Immunol 172:4091–4099

    PubMed  CAS  Google Scholar 

  18. Lehr HA, Mankoff DA, Corwin D, Santeusanio G, Gown AM (1997) Application of Photoshop-based image analysis to quantification of hormone receptor expression in breast cancer. J Histochem Cytochem 45:1559–1565

    Article  PubMed  CAS  Google Scholar 

  19. Pham NA, Morrison A, Schwock J et al (2007) Quantitative image analysis of immunohistochemical stains using a CMYK color model. Diagn Pathol. doi:10.1186/1746-1596-2-8

    PubMed  Google Scholar 

  20. Emile JF, Wechsler J, Brousse N et al (1995) Langerhans’ cell histiocytosis. Definitive diagnosis with the use of monoclonal antibody O10 on routinely paraffin-embedded samples. Am J Surg Pathol 19:636–641

    Article  PubMed  CAS  Google Scholar 

  21. Ramachandran IR, Song W, Lapteva N et al (2011) The phosphatase SRC homology region 2 domain-containing phosphatase-1 is an intrinsic central regulator of dendritic cell function. J Immunol 186:3934–3945

    Article  PubMed  CAS  Google Scholar 

  22. Yu RC, Abrams DC, Alaibac M, Chu AC (1994) Morphological and quantitative analyses of normal epidermal Langerhans cells using confocal scanning laser microscopy. Br J Dermatol 131:843–848

    Article  PubMed  CAS  Google Scholar 

  23. Jaffe R (2005) The diagnostic histopathology of Langerhans cell histiocytosis. In: Weitzman S, Egeler M (eds) Histiocytic disorders of children and adults. Cambridge University Press, Cambridge, pp 14–39

    Google Scholar 

  24. Jaffe R, Weiss LM, Facchetti F (2008) Tumours derived from Langerhans cells. In: Swerdlow SH, Campo E, Harris NL et al (eds) WHO classification of tumors of haematopoietic and lymphoid tissues, 4th edn. IARC, Lyon, pp 358–360

    Google Scholar 

  25. Bank MI, Rengtved P, Carstensen H, Petersen BL (2003) Langerhans cell histiocytosis: an evaluation of histopathological parameters, demonstration of proliferation by Ki-67 and mitotic bodies. APMIS 111:300–308

    Article  PubMed  Google Scholar 

  26. Shamoto M, Osada A, Shinzato M, Kaneko C, Shimizu M (1995) A comparative study on Langerhans cells in lymph nodes with dermatopathic lymphadenopathy and histiocytosis X cells. Adv Exp Med Biol 378:139–141

    PubMed  CAS  Google Scholar 

  27. Shultz LD, Schweitzer PA, Rajan TV et al (1993) Mutations at the murine motheaten locus are within the hematopoietic cell protein-tyrosine phosphatase (Hcph) gene. Cell 73:1445–1454

    Article  PubMed  CAS  Google Scholar 

  28. Nakayama K, Takahashi K, Shultz LD, Miyakawa K, Tomita K (1997) Abnormal development and differentiation of macrophages and dendritic cells in viable motheaten mutant mice deficient in haematopoietic cell phosphatase. Int J Exp Pathol 78:245–257

    Article  PubMed  CAS  Google Scholar 

  29. Sprecher E, Becker Y, Kraal G, Hall E, Shultz LD (1990) Effect of genetically determined immunodeficiency on epidermal dendritic cell populations in C57BL/6 J mice. Arch Dermatol Res 282:188–193

    Article  PubMed  CAS  Google Scholar 

  30. Wellbrock C, Karasarides M, Marais R (2004) The RAF proteins take centre stage. Nat Rev Mol Cell Biol 5:875–885

    Article  PubMed  CAS  Google Scholar 

  31. Lahlou H, Saint-Laurent N, Estève JP et al (2003) sst2 Somatostatin receptor inhibits cell proliferation through Ras-, Rap1-, and B-Raf-dependent ERK2 activation. J Biol Chem 278:39356–39371

    Article  PubMed  CAS  Google Scholar 

  32. Reth M, Brummer T (2004) Feedback regulation of lymphocyte signalling. Nat Rev Immunol 4:269–277

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was partly supported by a grant from Hamazaki Cancer Fund. We thank Dr. Daiichiro Hasegawa (Hyogo Children’s Hospital), Dr. Chihiro Shimazaki (Kyoto Prefectural University of Medicine), Dr. Nobuyo Yoshida (Kagoshima University Graduate School of Medicine and Dental Sciences), Dr. Teruhisa Koyama (NHO Okayama Medical Center), Dr. Sanae Kawakami (Ehime University School of Medicine), Dr. Takashi Kanazawa (Gunma University School of Medicine), Dr. Toshinori Hori (Aichi Medical University), Dr. Takashi Sato (Hiroshima University), Dr. Yoshiyuki Kosaka (Hyogo Children’s Hospital), Dr. Chihaya Imai (Niigata University), Dr. Banryoku Higuchi (Nara Medical University), Dr. Keigo Hamahata (Japanese Wakayama Red Cross Medical Center), Dr. Yutaka Kobayshi (Kyoto Second Red Cross Hospital), Dr. Ritsuo Nishiuchi (Kochi Medical Center), Dr. Yasuo Horikoshi (Shizuoka Prefectural Children’s Hospital), Dr. Yoshihiko Hoshida (Sumitomo Hospital), Dr. Kunimitsu Kawahara (Osaka Prefectural Medical Center for Respiratory and Allergic Diseases), Dr. Ichiro Yamadori (NHO Okayama Medical Center), Dr. Nobuya Ohara (Okayama Red Cross Hospital), Dr. Yasushi Horie (Tottori University Hospital), Dr. Francis Jaubert (Hôpital Necker-Enfants-Malades), Dr. Takehiro Tanaka, Dr. Koichi Ichimura, and Dr. Hiroyuki Yanai (Okayama University Hospital) for providing clinical information and specimens and Dr. Kenji Yokota (Okayama University Graduate School of Health Sciences) and the Central Research Laboratory, Okayama University Medical School for the help with the microscopes and software.

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We declare that we have no conflict of interest.

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Murakami, I., Oka, T., Kuwamoto, S. et al. Tyrosine phosphatase SHP-1 is expressed higher in multisystem than in single-system Langerhans cell histiocytosis by immunohistochemistry. Virchows Arch 459, 227–234 (2011). https://doi.org/10.1007/s00428-011-1090-1

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