Lack of expression of c-KIT in ovarian cancers is associated with poor prognosis

Tonary, Angela M.; Macdonald, Elizabeth; Faught, Wylam; Senterman, Mary K.; Vanderhyden, Barbara C.

doi:10.1002/1097-0215(20000520)89:3<242::aid-ijc6>3.0.co;2-6

Cited by 80 publications

(50 citation statements)

References 26 publications

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“…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. On the other hand, the prognostic value of the c-kit expression was demonstrated based on multivariate analyses for nueroblastomas (Krams et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…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%

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

et al. 2006

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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.

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Section: Discussionmentioning

confidence: 99%

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

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“…CD117 CD117, expressed in over 70% of EOC (Tonary et al 2000), was found as a single marker to enrich for TICs derived from human EOC cell xenografts (Luo et al 2011). The penetrance of tumourigenicity of the CD117-expressing cells was 33% when 1000 cells were injected, suggesting that CD117 alone afforded only a modest enrichment of TICs.…”

Section: Cd133mentioning

confidence: 99%

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Garson¹,

Vanderhyden²

2015

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The lack of significant progress in the treatment of epithelial ovarian cancer (EOC) underscores the need to gain a better understanding of the processes that lead to chemoresistance and recurrence. The cancer stem cell (CSC) hypothesis offers an attractive explanation of how a subpopulation of cells within a patient's tumour might remain refractory to treatment and subsequently form the basis of recurrent chemoresistant disease. This review examines the literature defining somatic stem cells of the ovary and fallopian tube, two tissues that give rise to EOC. In addition, considerable research has been reviewed, that has identified subpopulations of EOC cells, based on marker expression (CD133, CD44, CD117, CD24, epithelial cell adhesion molecule, LY6A, ALDH1 and side population (SP)), which are enriched for tumour initiating cells (TICs). While many studies identified either CD133 or CD44 as markers useful for enriching for TICs, there is little consensus. This suggests that EOC cells may have a phenotypic plasticity that may preclude the identification of universal markers defining a CSC. The assay that forms the basis of quantifying TICs is the xenograft assay. Considerable controversy surrounds the xenograft assay and it is essential that some of the potential limitations be examined in this review. Highlighting such limitations or weaknesses is required to properly evaluate data and broaden our interpretation of potential mechanisms that might be contributing to the pathogenesis of ovarian cancer.

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“…This has raised hopes that some carcinomas could be treated with imatinib mesylate. In ovarian carcinomas, the reported frequency of KIT and PDGFRA expression has been highly variable, and little is known about their molecular background and association with clinical parameters (Henriksen et al, 1993;Inoue et al, 1994;Arber et al, 1998;Dabrow et al, 1998;Parrott et al, 2000;Tonary et al, 2000;Schmandt et al, 2003;Singer et al, 2003;Apte et al, 2004a;Matei et al, 2004). GISTs with KIT mutation, particularly in exon 11, show a clearly better response to imatinib therapy as compared to tumours with no mutation, suggesting that detection of gain-of-function mutation and not solely KIT expression should be a requirement for the treatment (Heinrich et al, 2003).…”

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confidence: 99%

Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

et al. 2004

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KIT and PDGFRA are receptor tyrosine kinases that can be specifically inactivated by small-molecule tyrosine kinase inhibitors, notably imatinib mesylate. In ovarian carcinoma, expression of KIT and PDGFRA protein has been documented, but the frequency and the molecular background of expression are poorly known. We analysed the expression of KIT and PDGFRA by immunohistochemistry in 522 serous ovarian carcinomas, and mutations of KIT and PDGFRA by denaturing high-performance liquid chromatographyin 125 and 187 serous ovarian carcinomas, respectively. No mutations of KIT or PDGFRA were detected. KIT expression was detected in 12% of carcinomas: low expression in 10% and high expression in 2% of cases. Using normal serous epithelium as a reference, decreased PDGFRA expression was detected in 12% and increased expression in 13% of carcinomas. Both KIT and PDGFRA expression were associated with high tumour grade, high proliferation index and poor patient outcome. By fluorescence in situ hybridisation, no KIT amplification was found in carcinomas with high KIT expression, but two cases showed a relative gain of chromosome 4. In conclusion, no mutations of KIT or PDGFRA were found, but a subset of serous ovarian carcinoma showed overexpression of the proteins, which was associated with aggressive tumour characteristics.

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Lack of expression of c-KIT in ovarian cancers is associated with poor prognosis

Cited by 80 publications

References 26 publications

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

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

Epithelial ovarian cancer stem cells: underlying complexity of a simple paradigm

Genetic alterations and protein expression of KIT and PDGFRA in serous ovarian carcinoma

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