c-Kit expression in patients with uterine leiomyosarcomas: a potential alternative therapeutic treatment.
OBJECTIVE
Uterine leiomyosarcomas are rare tumors characterized by their resistance to chemotherapy and radiation treatment. Surgery is the primary method of treatment, but for patients with unresectable disease, alternate therapeutic options are clearly warranted. According to initial observations of c-KIT expression, correlation with a bad prognosis, and the successful therapeutic possibility of STI571 in gastrointestinal stromal tumors, the data have encouraged us to study c-KIT expression in these tumors.


METHODS
We analyzed the expression of c-KIT and genetic assessment of exon 11 of c-kit gene in 32 uterine leiomyosarcomas.


RESULTS
In 17 cases (53.1%), we observed a c-KIT expression in tumor cells. Of the 17 patients with distinct c-KIT-positive immunoreactivity, eight had I or II stage disease and nine had III or IV stage disease. Molecular genetic analysis of exon 11, analyzed by direct DNA sequencing, was performed for all of the c-KIT-positive uterine leiomyosarcomas. No mutations were found.


CONCLUSIONS
The conventional chemotherapy in leiomyosarcomas appears to be ineffective for patients with metastatic or unresectable disease, and the management of these patients poses a special problem. In these women, new therapeutic strategies are warranted. The treatment with STI571 in leiomyosarcoma patients might be hypothesized, because uterine leiomyosarcomas also express c-KIT.
Raspollini
Maria Rosaria
MR
Department of Human Pathology and Oncology, University of Florence, Florence, Italy. mariarosaria.raspolini@unifi.it
Amunni
Gianni
G
Villanucci
Alessandro
A
Pinzani
Pamela
P
Simi
Lisa
L
Paglierani
Milena
M
Taddei
Gian Luigi
GL
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology; D001549:Benzamides; D004247:DNA / Q000378:metabolism; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000068877:Imatinib Mesylate; D007150:Immunohistochemistry; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D008875:Middle Aged; D010879:Piperazines / Q000494:pharmacology; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D011743:Pyrimidines / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D004247:DNA; D019009:Proto-Oncogene Proteins c-kit