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KIT protein expression in uterine sarcomas: an immunohistochemical study and review of the literature
11st Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, Greece
2Department of Pathology, “Hippokration” General Hospital, Thessaloniki, Greece
*Corresponding Author(s): M. Zafrakas E-mail: mzafrakas@gmail.com
Purpose: The aim of the present study was to investigate the possibility of treating uterine sarcomas with imatinib mesylate. Imatinib mesylate, a selective tyrosine kinase inhibitor, is very efficient against mesenchymal tumors of the gastrointestinal tract, known as GISTs. Imatinib mesylate acts against a tyrosine kinase encoded by the KIT gene in GISTs, and is more effective in tumors expressing this protein. Methods: Expression of KIT was analyzed immunohistochemically (n = 12) in formalin-fixed paraffin-embedded primary uterine sarcomas. Results: Using a semi-quantitative immunohistochemical score we found that KIT expression was very weak in the majority of tumors, while none of the uterine sarcomas tested showed strong expression. Overall, published studies addressing this issue in small series of uterine sarcomas yielded similar results. Conclusion: Current data suggest that it is unlikely that imatinib mesylate could be used effectively as a single agent in patients with uterine sarcomas.
Uterine sarcoma; KIT; Imatinib mesylate
M. Zafrakas,T.D. Theodoridis,L. Zepiridis,I.D. Venizelos,T. Agorastos,J. Bontis. KIT protein expression in uterine sarcomas: an immunohistochemical study and review of the literature. European Journal of Gynaecological Oncology. 2008. 29(3);264-266.
[1] Forney J.P., Buschbaum H.J.: “Classifying, staging, and treating uterine sarcomas”. Contemp. Obstet. Gynecol., 1981, 18, 47.
[2] Nordal R.R., Thoreson S.O.: “Uterine sarcomas in Norway 1956-1992: incidence, survival and mortality”. Eur. J. Cancer, 1997, 33, 907.
[3] Kanjeekal S., Chambers A., Fung M.F., Verma S.: “Systemic therapy for advanced uterine sarcoma: a systematic review of the literature”. Gynecol. Oncol., 2005, 97, 624.
[4] Benoit L., Arnould L., Cheynel N., Goui S., Collin F., Fraisse J.,Cuisenier J.: “The role of surgery and treatment trends in uterine sarcoma”. Eur. J. Surg. Oncol., 2005, 31, 434.
[5] Menczer J., Levy T., Piura B. et al.: “A comparison between different postoperative treatment modalities of uterine carcinosarcoma”. Gynecol. Oncol., 2005, 97, 166.
[6] Joensuu H., Roberts P.J., Sarlomo-Rikala M. et al.: “Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor”. N. Engl. J. Med., 2001, 344, 1052.
[7] van Oosterom A.T., Judson I., Verweij J., Stroobants S., Donato di Paola E., Dimitrijevic S. et al.: “Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study”. Lancet, 2001, 358, 1421.
[8] Demetri G.D., von Mehren M., Blanke C.D., Van den Abbeele A.D., Eisenberg B., Roberts P.J. et al.: “Efficacy and safety of Imatinib mesylate in advanced gastrointestinal stromal tumors”. N. Engl. J. Med., 2002, 347, 472.
[9] de Mestier P., des Guetz G.: “Treatment of gastrointestinal stromal tumors with imatinib mesylate: a major breakthrough in the understanding of tumor-specific molecular characteristics”. World J. Surg., 2005, 29, 357.
[10] Remmele W., Stegner H.E.: “Recommendation for uniform definition of an immunoreactive score (IRS) for immunohistochemical estrogen receptor detection (ERICA) in breast cancer tissue”. Pathologe, 1987, 8, 138.
[11] Savage D.G., Antman K.H.: “Imatinib mesylate - a new oral targeted therapy”. N. Engl. J. Med., 2002, 2346, 683.
[12] Hirota S., Isozaki K., Moriyama Y. et al.: “Gain of function mutations of c-kit in human gastrointestinal stromal tumors”. Science, 1998, 279, 577.
[13] Winter W.E. 3rd, Seidman J.D., Krivak T.C. et al.: “Clinicopathological analysis of c-kit expression in carcinosarcomas and leiomyosarcomas of the uterine corpus”. Gynecol. Oncol., 2003, 91, 3.
[14] Klein W.M., Kurman R.J.: “Lack of expression of c-kit protein (CD117) in mesenchymal tumors of the uterus and ovary”. Int. J. Gynecol. Pathol., 2003, 22, 181.
[15] Nakayama M., Mitsuhashi T., Shimizu Y., Ban S., Ogawa F., Ishihara O., Shimizu M.: “Immunohistochemical evaluation of KIT expression in sarcomas of the gynecologic region”. Int. J. Gynecol. Pathol., 2006, 25, 70.
[16] Sawada M., Tsuda H., Kimura M., Okamoto S., Kita T., Kasamatsu T. et al.: “Different expression patterns of KIT, EGFR, and HER-2 (c-erbB-2) oncoproteins between epithelial and mesenchymal components in uterine carcinosarcoma”. Cancer Sci 2003, 94, 986.
[17] Menczer J., Kravtsov V., Levy T., Berger E., Glezerman M., Avinoach I.: “Expression of c-kit in uterine carcinosarcoma”. Gynecol. Oncol., 2005, 96, 210.
[18] Raspollini M.R., Susini T., Amunni G., Paglierani Taddai A., Marchionni M., Scarselli G., Taddei G.L.: “COX-2, c-KIT and HER- 2/neu expression in uterine carcinosarcomas: prognostic factors or potential markers for targeted therapies?”. Gynecol. Oncol., 2005, 96, 159.
[19] Raspollini M.R., Amunni G., Villanucci A., Pinzani P., Simi L., Paglierani M., Taddei G.L.: “c-Kit expression in patients with uterine leiomyosarcomas: a potential alternative therapeutic treatment”. Clin. Cancer Res., 2004, 10, 3500.
[20] Serrano C., Mackintosh C., Herrero D., Martins A.S., de Alava E., Hernandez T.: “Imatinib is not a potential alternative treatment for uterine leiomyosarcoma”. Clin. Cancer Res., 2005, 11, 4977.
[21] Rushing R.S., Shajahan S., Chendil D. et al.: “Uterine sarcomas express KIT protein but lack mutation(s) in exon 11 or 17 of c-KIT”. Gynecol. Oncol., 2003, 91, 9.
[22] Leath C.A. 3rd, Straughn J.M. Jr, Conner M.G., Barnes M.N. 3rd, Alvarez R.D., Partridge E.E., Huh W.K.: “Immunohistochemical evaluation of the c-kit protooncogene in sarcomas of the uterus: a case series”. J. Reprod. Med., 2004, 49, 71.
[23] Went P.T., Dirnhofer S., Bundi M., Mirlacher M., Schrami P., Mangialaio S. et al.: “Prevalence of KIT expression in human tumors”. J. Clin. Oncol., 2004, 22, 4514.
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