Expression of the c-kit receptor characterizes a subset of neuroblastomas with favorable prognosis

Krams, Matthias; Parwaresch, Reza; Sipos, Bence; Heidorn, Klaus; Harms, D.; Rudolph, Pierre

doi:10.1038/sj.onc.1207145

Cited by 44 publications

(36 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…42) On the contrary, another report stated that cKit positive NBs have favorable prognoses based on the same immunohistochemical method. 43) Based on our findings, although the SCF mRNA expression had no prognostic value for our NB patients, surviving NB patients had high expression of c-kit mRNA compared with little or no c-kit expression in the NB patients who subsequently died. It is possible that NB tumor cells with c-kit expression-positive NB tumor cells can react with SCF (by autocrine or paracrine system), but tumor cells with no such expression can not react, and these tumors continue to be immature.…”

Section: Resultsmentioning

confidence: 99%

Analyses of Novel Prognostic Factors in Neuroblastoma Patients

Ootsuka

Asami

Sasaki

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

Section: Resultsmentioning

confidence: 99%

Analyses of Novel Prognostic Factors in Neuroblastoma Patients

Ootsuka

Asami

Sasaki

et al. 2007

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

“…The survival analyses for the c-kit expression have been demonstrated in several malignant tumours (Tonary et al, 2000;Bar-Sela et al, 2003;Scobie et al, 2003;Krams et al, 2004;Simon et al, 2004;Pan et al, 2005), while there was only one survival analysis (Simon et al, 2004) regarding breast cancer, in which no difference was found in the survival between the patients with or without the c-kit expression. Although no statistically significant difference in clinical outcomes has been found in endometrial adenocarcinomas (Scobie et al, 2003), nasopharygeal carcinomas (Bar-Sela et al, 2003) and small cell carcinomas of the urinary bladder (Pan et al, 2005), two studies on ovarian cancers (Tonary et al, 2000) and neuroblastomas (Krams et al, 2004) indicated an association between a loss of the c-kit expression and poor prognosis. In ovarian cancers, the loss of c-kit expression was associated with a poor prognosis, while the c-kit expression tended to decrease at an advanced stage (Tonary et al, 2000), being similar with our findings in breast cancers.…”

Section: Discussionmentioning

confidence: 99%

“…In ovarian cancers, the loss of c-kit expression was associated with a poor prognosis, while the c-kit expression tended to decrease at an advanced stage (Tonary et al, 2000), being similar with our findings in breast cancers. On the other hand, the prognostic value of the c-kit expression was demonstrated based on multivariate analyses for nueroblastomas (Krams et al, 2004). In the present study, a univariate analysis demonstrated the prognosis of the patients with a loss of the c-kit expression to be significantly worse than those with a positive c-kit expression, while a multivariate analysis demonstrated lymph node metastasis and a proliferative activity determined by MIB-1 counts, but not the c-kit expression, to be independently significant prognostic factors for DFS.…”

Section: Discussionmentioning

confidence: 99%

A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer

et al. 2006

View full text Add to dashboard Cite

To evaluate the c-kit expression in breast cancer, 217 invasive ductal carcinomas of the breast were immunohistochemically stained for c-kit protein. The c-kit expression was positive in 59 (27%) of 217 tumours, while the c-kit expression was negative in 158 (73%) of 217 tumours. There was a significant correlation between a negative expression of the c-kit protein and lymph node metastasis (Po0.0001), and the incidence of a negative expression of the c-kit protein increased as the number of the metastatic lymph nodes increased (P ¼ 0.0003). The c-kit expression did not significantly correlate with the tumour size, nuclear grade, oestrogen receptor status, MIB-1 counts and p53 protein expression. A univariate analysis indicated the patients with the negative c-kit expression to have a worse disease-free survival (DFS) than those with the positive c-kit expression (P ¼ 0.0041), while a multivariate analysis determined lymph node metastases and the MIB-1 counts to be independently significant factors for DFS. In conclusion, a loss of the c-kit expression was found in about three-fourth of invasive ductal carcinoma of the breast and was associated with lymph node metastases. The prognostic implications of the c-kit expression seem to be due to fact that a loss of the c-kit expression is associated with an advanced stage of breast cancer.

show abstract

“…Unlike in other tumors (57,58), the clinical impact of deregulated expression of this ligand/receptor system in CRC remains, at least in part, controversial. As a matter of fact, when KIT or SCF protein expression was analyzed separately, no significant association was found between either patient survival or disease recurrence.…”

Section: Discussionmentioning

confidence: 99%

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Bellone¹,

Smirne²,

Carbone³

et al. 2006

Int J Oncol

View full text Add to dashboard Cite

Abstract. Autocrine/paracrine stimulation of KIT has been observed in colorectal carcinoma (CRC) cell lines. We investigated the expression of KIT and stem cell factor (SCF) in CRC in comparison with premalignant colon lesions and normal colonic mucosa to assess the prognostic and therapeutic relevance of this receptor/ligand system in CRC. Transcript levels of c-kit and the two SCF splicing variants were determined quantitatively by real-time RT-PCR using cDNA obtained from normal, premalignant and malignant snap frozen colon tissue specimens. Immunohistochemistry with specific anti-KIT and anti-SCF antibodies was performed on paraffin-embedded tissue sections in order to localize the relative protein expression in epithelial compartments. Approximately 10% of patients expressed KIT in their adenoma or primary tumor. The majority of KIT-positive carcinomas co-expressed SCF. Real-time RT-PCR showed expression of c-kit and SCF transcripts in all cDNA specimens examined. A significant association between the co-expression of KIT/SCF and a worse clinical outcome was found. In conclusion, KIT expression was observed in a proportion of premalignant and malignant colonic lesions, while it was virtually absent in normal colon mucosa. Moreover, the majority of KIT-positive carcinomas co-expressed SCF, suggesting the possibility of aberrant signaling by an autocrine loop, as confirmed by the negative prognostic value of this association. Therefore, in the subset of CRC patients with concomitant KIT/SCF expression, the activity of Imatinib mesylate, a selective inhibitor of specific tyrosine kinases including KIT, may be exploited in combination with standard therapy.

show abstract

Expression of the c-kit receptor characterizes a subset of neuroblastomas with favorable prognosis

Cited by 44 publications

References 41 publications

Analyses of Novel Prognostic Factors in Neuroblastoma Patients

Analyses of Novel Prognostic Factors in Neuroblastoma Patients

A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer

KIT/stem cell factor expression in premalignant and malignant lesions of the colon mucosa in relationship to disease progression and outcomes

Contact Info

Product

Resources

About