Kit expression in male germ cell tumors.
OBJECTIVE
KIT functions as the receptor for stem cell factor (SCF) and this interaction is essential for regulation of proliferation and survival, particularly for germ cells since it regulates oogenesis, folliculogenesis and spermatogenesis. Up-regulation of KIT signalling has been associated with oncogenic transformation in cells expressing the molecule. Our objective was to investigate the expression of KIT in germ cell tumor patients and correlate it with the patients' clinical characteristics.


METHODS
One hundred and seventy-three archival blocks of formalin fixed, paraffin-embedded tumor samples from histologically confirmed germ cell tumor (GCT) patients were included in the study. Immunohistochemical staining for KIT was performed and the percentage of positive cells was calculated by an independent pathologist. KIT expression was considered as positive if > 10% of tumor cells displayed membranous or cytoplasmic staining.


RESULTS
Sixty-one patients with seminomatous (49 pure, 11 anaplastic, 1 spermocytic) and 112 with non-seminomatous GCTs (36 malignant teratoma undifferentiated (MTU), 15 malignant teratoma trophoblastic (MTT), 20 malignant teratoma intermediate (MTI), 35 malignant teratoma combined (MTC) and six others) were identified. Among pure seminoma patients, 38 (77.5%) revealed a positive staining for KIT, while only two out of eleven (18.2%) anaplastic seminoma patients were identified as positive. This difference was statistically significant (p < 0.001). Among 35 patients with an MTC, 48.6% had a positive KIT staining while only two of the remaining patients with a non-seminomatous GCT had a positive staining. Although KIT was strongly correlated with seminomatous histology (p < 0.001), it failed to correlate with stage (p = 0.19) or treatment response (p = 0.11) in these patients. Overall, four (one seminoma, three MTC) out of 22 chemoresistant patients showed a positive staining for KIT.


CONCLUSIONS
KIT is expressed in the majority of seminomas and in seminomatous components of the combined tumors, but only in a minority of anaplastic seminomas and rarely in non-seminomatous GCTs. The recent development of tyrosine kinase inhibitors may offer a possibility of cure in chemoresistant patients overexpressing KIT.
Nikolaou
M
M
Second Department of Internal Medicine-Propaedeutic, Attikon Hospital, Athens University Medical School, Greece. m_nikolaou@panafonet.gr
Valavanis
C
C
Aravantinos
G
G
Fountzilas
G
G
Tamvakis
N
N
Lekka
I
I
Arapantoni-Dadioti
P
P
Zizi
A
A
Ghiconti
I
I
Economopoulos
Th
T
Pectasides
D
D
D000293:Adolescent; D000328:Adult; D000368:Aged; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy / Q000473:pathology*; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis*; D015854:Up-Regulation
D019009:Proto-Oncogene Proteins c-kit