Expression of imatinib mesylate-targeted kinases in endometrial carcinoma

Brian Slomovitz, Russell R. Broaddus, Rosemarie Schmandt, Weiguo Wu, Jonathan C. Oh, Lois M. Ramondetta, Thomas W. Burke, David M. Gershenson, Karen H. Lu

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets c-Kit, Abl, and platelet-derived growth factor receptor (PDGFR). It has been shown to be an effective treatment for patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). These cancers are characterized by activating mutations of the Abl and c-Kit tyrosine kinases, respectively. To determine whether imatinib mesylate could be a potentially useful agent in the treatment of endometrial cancer, we assessed the expressions of Abl, c-Kit, and PDGFR in both primary and recurrent endometrial carcinoma. We performed immunohistochemical analysis on formalin-fixed, paraffin-embedded sections from 63 patients: 33 with endometrioid endometrial carcinoma (EEC), 11 with uterine papillary serous carcinoma (UPSC), 12 with recurrent EEC, and seven with recurrent UPSC. The sections were stained with commercially available antibodies for Abl, PDGFR, and c-Kit. The sections were also stained for phosphorylated Abl and phosphorylated PDGFR. Among the primary EEC, 28/33 (85%) stained positively for Abl and 30/33 (91%) were positive for PDGFR. Of the primary UPSC, 8/11 (73%) were positive for Abl. In addition, 8/11 (73%) of the primary UPSC tumors were positive for PDGFR. Neither the primary EEC (0/33) nor the primary UPSC (0/11) expressed c-Kit. Of the recurrent EEC tumors, 11/12 (92%) were positive for Abl expression, 12/12 (100%) were positive for PDGFR, and 2/8 (25%) were positive for c-Kit. Of the recurrent UPSC, 6/7 (86%) were positive for Abl, 7/7 (100%) were positive for PDGFR, and 2/4 (50%) for c-Kit. In addition, the majority of primary and recurrent tumors were positive for phosphorylated Abl (primary EEC, 91%; primary UPSC, 64%; recurrent EEC, 83%; recurrent UPSC, 86%), and phosphorylated PDGFR (primary EEC, 46%; primary UPSC, 40%; recurrent EEC, 58%; recurrent UPSC, 100%). Within the EEC primary tumors, the differences in kinase expression by grade of tumor were not significant except for PDGFR kinase; the lower grade tumors (1 and 2) had more PDGFR expression than the grade 3 tumors (P < 0.05). The majority of primary and recurrent EEC, as well as primary and recurrent UPSC express Abl and PDGFR. This preclinical data suggest that imatinib mesylate may be useful in the treatment of patients with endometrial carcinoma.

Original languageEnglish (US)
Pages (from-to)32-36
Number of pages5
JournalGynecologic Oncology
Volume95
Issue number1
DOIs
StatePublished - Oct 2004
Externally publishedYes

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Platelet-Derived Growth Factor Receptors
Endometrioid Carcinoma
Endometrial Neoplasms
Papillary Carcinoma
Phosphotransferases
Neoplasms
Imatinib Mesylate
Protein-Tyrosine Kinases
Gastrointestinal Stromal Tumors
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Paraffin
Formaldehyde
Therapeutics

Keywords

  • Abl
  • Endometrial carcinoma
  • Imatinib mesylate
  • PDGFR
  • Uterine papillary serous carcinoma

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Slomovitz, B., Broaddus, R. R., Schmandt, R., Wu, W., Oh, J. C., Ramondetta, L. M., ... Lu, K. H. (2004). Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. Gynecologic Oncology, 95(1), 32-36. https://doi.org/10.1016/j.ygyno.2004.06.052

Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. / Slomovitz, Brian; Broaddus, Russell R.; Schmandt, Rosemarie; Wu, Weiguo; Oh, Jonathan C.; Ramondetta, Lois M.; Burke, Thomas W.; Gershenson, David M.; Lu, Karen H.

In: Gynecologic Oncology, Vol. 95, No. 1, 10.2004, p. 32-36.

Research output: Contribution to journalArticle

Slomovitz, B, Broaddus, RR, Schmandt, R, Wu, W, Oh, JC, Ramondetta, LM, Burke, TW, Gershenson, DM & Lu, KH 2004, 'Expression of imatinib mesylate-targeted kinases in endometrial carcinoma', Gynecologic Oncology, vol. 95, no. 1, pp. 32-36. https://doi.org/10.1016/j.ygyno.2004.06.052
Slomovitz, Brian ; Broaddus, Russell R. ; Schmandt, Rosemarie ; Wu, Weiguo ; Oh, Jonathan C. ; Ramondetta, Lois M. ; Burke, Thomas W. ; Gershenson, David M. ; Lu, Karen H. / Expression of imatinib mesylate-targeted kinases in endometrial carcinoma. In: Gynecologic Oncology. 2004 ; Vol. 95, No. 1. pp. 32-36.
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abstract = "Imatinib mesylate is a tyrosine kinase inhibitor that specifically targets c-Kit, Abl, and platelet-derived growth factor receptor (PDGFR). It has been shown to be an effective treatment for patients with chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). These cancers are characterized by activating mutations of the Abl and c-Kit tyrosine kinases, respectively. To determine whether imatinib mesylate could be a potentially useful agent in the treatment of endometrial cancer, we assessed the expressions of Abl, c-Kit, and PDGFR in both primary and recurrent endometrial carcinoma. We performed immunohistochemical analysis on formalin-fixed, paraffin-embedded sections from 63 patients: 33 with endometrioid endometrial carcinoma (EEC), 11 with uterine papillary serous carcinoma (UPSC), 12 with recurrent EEC, and seven with recurrent UPSC. The sections were stained with commercially available antibodies for Abl, PDGFR, and c-Kit. The sections were also stained for phosphorylated Abl and phosphorylated PDGFR. Among the primary EEC, 28/33 (85{\%}) stained positively for Abl and 30/33 (91{\%}) were positive for PDGFR. Of the primary UPSC, 8/11 (73{\%}) were positive for Abl. In addition, 8/11 (73{\%}) of the primary UPSC tumors were positive for PDGFR. Neither the primary EEC (0/33) nor the primary UPSC (0/11) expressed c-Kit. Of the recurrent EEC tumors, 11/12 (92{\%}) were positive for Abl expression, 12/12 (100{\%}) were positive for PDGFR, and 2/8 (25{\%}) were positive for c-Kit. Of the recurrent UPSC, 6/7 (86{\%}) were positive for Abl, 7/7 (100{\%}) were positive for PDGFR, and 2/4 (50{\%}) for c-Kit. In addition, the majority of primary and recurrent tumors were positive for phosphorylated Abl (primary EEC, 91{\%}; primary UPSC, 64{\%}; recurrent EEC, 83{\%}; recurrent UPSC, 86{\%}), and phosphorylated PDGFR (primary EEC, 46{\%}; primary UPSC, 40{\%}; recurrent EEC, 58{\%}; recurrent UPSC, 100{\%}). Within the EEC primary tumors, the differences in kinase expression by grade of tumor were not significant except for PDGFR kinase; the lower grade tumors (1 and 2) had more PDGFR expression than the grade 3 tumors (P < 0.05). The majority of primary and recurrent EEC, as well as primary and recurrent UPSC express Abl and PDGFR. This preclinical data suggest that imatinib mesylate may be useful in the treatment of patients with endometrial carcinoma.",
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