c-Kit Expression in Patients with Uterine Leiomyosarcomas

Raspollini, Maria Rosaria; Amunni, Gianni; Villanucci, A.; Pinzani, Pamela; Simi, Lisa; Paglierani, Milena; Taddei, Gian Luigi

doi:10.1158/1078-0432.ccr-03-0363

Cited by 48 publications

(26 citation statements)

References 14 publications

(8 reference statements)

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“…However, the possibility to use this marker to select patients for innovative targeted therapies using STI571 need to be demonstrated. The immunohistochemical overexpression of c-KIT has been reported also in other malignances such as small cell lung cancer [36] and uterine leiomyosarcomas [37]. Our previous study on c-KIT expression in uterine leiomyosarcomas failed to detect any mutation in exon 11 of the c-kit gene [37].…”

Section: Discussionmentioning

confidence: 85%

“…The immunohistochemical overexpression of c-KIT has been reported also in other malignances such as small cell lung cancer [36] and uterine leiomyosarcomas [37]. Our previous study on c-KIT expression in uterine leiomyosarcomas failed to detect any mutation in exon 11 of the c-kit gene [37]. Therefore, the site of c-kit gene mutation and whether uterine carcinosarcoma patients may respond to KIT inhibition remain to be established and these are questions for future studies.…”

Section: Discussionmentioning

confidence: 97%

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COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Raspollini

Susini

Amunni

et al. 2005

Gynecologic Oncology

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Objectives. Uterine carcinosarcomas are uncommon, highly aggressive neoplasms that frequently recur after surgical treatment and adjuvant chemo-radiotherapy. Patients with recurrent disease respond poorly to salvage chemotherapy and irradiation. New therapeutic options are required for patients with metastatic disease. Clinical evidences showing the effect of a tyrosine kinase inhibitor, STI571, in c-KIT-positive gastrointestinal tumors, the role of COX-inhibitors chemotherapy-associated in colorectal cancer patients and the successful therapeutic possibility of anti-HER2 therapy in metastatic breast carcinoma, have encouraged us to study the expression of c-KIT, COX-2 and HER-2/neu in uterine carcinosarcomas.Methods. We analyzed the expression of COX-2, c-KIT and HER-2/neu in 24 uterine carcinosarcomas and their correlation with clinical outcome. Disease-free interval and actuarial survival rates were the end points of the study.Results. High staining intensity for COX-2 was observed in 8 cases (33.3%). C-KIT was expressed in 4 cases (16.7%) and HER-2/neu in 7 cases (29.2%). Patients with COX-2-positive tumors had a significantly poorer disease-free interval and survival ( P = 0.01 and P = 0.05, respectively). All patients with c-KIT-positive tumors had early stage disease. In spite of this, their survival was not significantly better than that of c-KIT-negative cases. HER-2/neu expression did not show any correlation with clinical outcome.Conclusion. c-KIT, COX-2, and HER-2/neu were expressed in different proportions of uterine carcinosarcomas. COX-2 expression was a strong indicator of unfavorable prognosis. These results warrant further study to evaluate the possible role of a new molecularly targeted cancer therapy with COX-2 inhibitors in patients with uterine carcinosarcomas. The role of c-KIT expression and consequently the hypothetical use of STI571 should be tested in a larger series.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 97%

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Raspollini

Susini

Amunni

et al. 2005

Gynecologic Oncology

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“…Other studies note the wide distribution of mast cells in the uterus (29,30), and some authors have proved that stem cell factor and its receptor c-Kit have been use to study the modulation of tumor angiogenesis in breast cancer cells and prognosis in leiomyosarcomas. Also, that can be used as possible targets for anticancer drug therapies (31,32). Our results show a very intense reaction only for ER␤ in the granules of these cells.…”

Section: Valladares Estrogen Receptors In Leiomyoma Cells Fertil Stmentioning

confidence: 99%

Characterization of estrogen receptors alpha and beta in uterine leiomyoma cells

Valladares

Frı́as

Báez

et al. 2006

Fertility and Sterility

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“…There has been recent evidence demonstrating c-kit proto-oncogene overexpression in leiomyosarcomas of the thyroid and uterus (11,17,18). C-kit is a 145 kDa transmembrane tyrosine kinase receptor involved in cell signal transduction.…”

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confidence: 99%

“…C-kit expression has been identified in a number of different neoplasms, including gastrointestinal stromal tumors (GIST), in which tyrosine kinase inhibitors (i.e., imatinib mesylate, or Gleevac) have been an effective treatment. To date, however, the use of tyrosine kinase inhibitors has not been effective in treating uterine leiomyosarcomas (17,18). Imatinib mesylate was used as an adjuvant treatment in one patient who presented with a high-grade leiomyosarcoma of the thyroid and lung metastases.…”

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Primary Leiomyosarcoma of the Thyroid Gland

Wang

Ocal

Oxley

et al. 2008

Thyroid

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Primary leiomyosarcomas of the thyroid gland are rare. We present the case of a 65-year-old woman with a rapidly enlarging neck mass for 2 months. The preoperative differential diagnosis included medullary thyroid cancer, anaplastic thyroid cancer, and primary versus metastatic sarcoma. The patient underwent total thyroidectomy, bilateral central neck dissections, and cervical thymectomy; she is currently being treated with ifosfamide and adriamycin. We review the literature on leiomyosarcoma of the thyroid, including the differential diagnoses, pathology, and alternative treatment strategies, including surgery and adjuvant therapy.

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c-Kit Expression in Patients with Uterine Leiomyosarcomas

Cited by 48 publications

References 14 publications

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

COX-2, c-KIT and HER-2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?

Characterization of estrogen receptors alpha and beta in uterine leiomyoma cells

Primary Leiomyosarcoma of the Thyroid Gland

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