Literature DB >> 12893208

The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus.

Lina Wang1, Juan C Felix, Joyce L Lee, Peik Y Tan, David E Tourgeman, Anne T O'Meara, Charles A Amezcua.   

Abstract

OBJECTIVE: The proto-oncogene c-kit encodes for a 145-kDa transmembrane tyrosine kinase receptor. Interaction with its ligand, stem cell factor, is essential in the development of hematopoietic stem cells, mast cells, gametocytes, melanocytes, and interstitial cells of Cajal. C-kit expression has been identified in a number of different neoplasms that includes mastocytosis/mast cell leukemia, acute myeloblastic leukemia, seminoma/dysgerminoma, and gastrointestinal stromal tumors. This study examines c-kit expression in uterine endometrial stromal sarcomas, leiomyomas, and leiomyosarcomas using immunohistochemistry.
METHODS: Archival tissue from 38 patients with the uterine mesenchymal tumors (16 leiomyosarcomas, 8 leiomyomas, 11 low-grade endometrial stromal sarcomas, and 3 high-grade endometrial stromal sarcomas) was stained with polyclonal antibody for c-kit. Modified avidin biotin (ABC) immunoperoxidase method was employed for antibody detection. Individual tumors were considered positive if more than 10% of the cells comprising the neoplasm displayed immunoreactive staining. Staining intensity was graded 1+ to 3+ and distribution graded as focal (10-30% of the cells), intermediate (30-60% of the cells), or diffuse (>60% of the cells).
RESULTS: C-kit was positive in 12 (75%) of the 16 leiomyosarcomas. The staining was 3+ and diffuse in the majority of the positive tumors. C-kit expression was not detected in any of the 8 leiomyomas. Two of the 3 high-grade endometrial stromal sarcomas displayed c-kit positivity. Staining was diffuse and 3+ in both of these tumors. Expression of c-kit was observed in only 3 of the 11 low-grade endometrial stromal sarcomas.
CONCLUSIONS: C-kit is expressed in uterine leiomyosarcomas and endometrial stromal sarcomas. Adjunctive diagnostic studies using c-kit may be useful in distinguishing leiomyosarcomas from benign leiomyomas in uterine tumors that offer uncharacteristic features. Furthermore, studies should investigate the prospect of treating these malignant tumors with tyrosine kinase inhibitors.

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Year:  2003        PMID: 12893208     DOI: 10.1016/s0090-8258(03)00274-9

Source DB:  PubMed          Journal:  Gynecol Oncol        ISSN: 0090-8258            Impact factor:   5.482


  12 in total

Review 1.  Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma.

Authors:  Takuma Hayashi; Akiko Horiuchi; Kenji Sano; Nobuyoshi Hiraoka; Yae Kanai; Tanri Shiozawa; Susumu Tonegawa; Ikuo Konishi
Journal:  Protein Cell       Date:  2010-08-28       Impact factor: 14.870

2.  Constitutive activation with overexpression of the mTORC2-phospholipase D1 pathway in uterine leiomyosarcoma and STUMP: morphoproteomic analysis with therapeutic implications.

Authors:  Sadhna Dhingra; Michelle E Rodriguez; Qi Shen; Xuizhen Duan; Melissa L Stanton; Lei Chen; Rongzhen Zhang; Robert E Brown
Journal:  Int J Clin Exp Pathol       Date:  2010-01-28

3.  Uterine leiomyosarcoma management, outcome, and associated molecular biomarkers: a single institution's experience.

Authors:  Kristelle Lusby; Kari Brewer Savannah; Elizabeth G Demicco; Yiqun Zhang; Markus Ph Ghadimi; Eric D Young; Chiara Colombo; Ryan Lam; Tugce E Dogan; Jason L Hornick; Alexander J Lazar; Kelly K Hunt; Matthew L Anderson; Chad J Creighton; Dina Lev; Raphael E Pollock
Journal:  Ann Surg Oncol       Date:  2013-01-20       Impact factor: 5.344

Review 4.  Genetic aberrations in soft tissue leiomyosarcoma.

Authors:  Jilong Yang; Xiaoling Du; Kexin Chen; Antti Ylipää; Alexander J F Lazar; Jonathan Trent; Dina Lev; Raphael Pollock; Xishan Hao; Kelly Hunt; Wei Zhang
Journal:  Cancer Lett       Date:  2008-07-22       Impact factor: 8.679

5.  Over-expression of c-kit in a primary leiomyosarcoma of the thyroid gland.

Authors:  An-Shiou Day; Pei-Jen Lou; Wei-Chou Lin; Chi-Chun Chou
Journal:  Eur Arch Otorhinolaryngol       Date:  2007-01-26       Impact factor: 3.236

6.  Uterine C-Kit positive low grade stromal sarcoma.

Authors:  Jovitha Martin; Anita Ramesh; Sarah Kuruvilla; D Lalitha
Journal:  Indian J Med Paediatr Oncol       Date:  2009-07

7.  Molecular Approach to Uterine Leiomyosarcoma: LMP2-Deficient Mice as an Animal Model of Spontaneous Uterine Leiomyosarcoma.

Authors:  Takuma Hayashi; Akiko Horiuchi; Kenji Sano; Nobuyoshi Hiraoka; Yae Kanai; Tanri Shiozawa; Susumu Tonegawa; Ikuo Konishi
Journal:  Sarcoma       Date:  2011-03-08

8.  Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy.

Authors:  Takuma Hayashi; Akiko Horiuchi; Kenji Sano; Nobuyoshi Hiraoka; Mari Kasai; Tomoyuki Ichimura; Tamotsu Sudo; Yoh-Ichi Tagawa; Ryuichiro Nishimura; Osamu Ishiko; Yae Kanai; Nobuo Yaegashi; Hiroyuki Aburatani; Tanri Shiozawa; Ikuo Konishi
Journal:  Sci Rep       Date:  2011-12-05       Impact factor: 4.379

9.  Molecular mechanisms of uterine leiomyosarcomas: involvement of defect in LMP2 expression.

Authors:  Takuma Hayashi; Yuto Shimamura; Taro Saegusa; Akiko Horiuchi; Yukihiro Kobayashi; Nobuyoshi Hiraoka; Yae Kanai; Hiroyuki Aburatani; Kenji Sano; Ikuo Konishi
Journal:  Gene Regul Syst Bio       Date:  2008-07-22

10.  Endometrial stromal tumors: immunohistochemical and molecular analysis of potential targets of tyrosine kinase inhibitors.

Authors:  Carmen Balañá; Enrique de Álava; Ruth Sardinha; Teresa Hernández; Susana Fraile; Francesc Tresserra; August Vidal; Maria Carmén Gómez; Aurora Astudillo; Nieves Hernández; Javier Saenz de Santamaría; Jaume Ordi; Luis Gonçalves; Rafael Ramos
Journal:  Clin Sarcoma Res       Date:  2013-03-07
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