Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients' outcome

Abstract

BACKGROUND: c Kit (CD117) expression in tissues has been reported as a relevant target for specific therapy in some human malignancies, but has been poorly documented in breast carcinomas METHODS: The prognostic significance of c Kit in a series of 924 breast carcinomas (mean follow-up, 79 months) was investigated using standardised high-throughput quantitative densitometry of immunohistochemical precipitates in tissue microarrays. RESULTS: c Kit was expressed in 14.7% breast carcinomas (and in 42 out of 586 node-negative tumours). In univariate analysis, (log-rank test) the score of c Kit expression correlated with poor patient outcome P ¼ 0.02 and particularly in node-negative cases (P ¼ 0.002). In multivariate Cox analysis, c Kit was an indicator of metastasis independent of 25 other concomitantly evaluated markers of prognosis. Logistic regression showed that c Kit ranked 10 out of 25 (P ¼ 0.041), and was included in a 10-marker signature that allowed 79.2% of the patients to be correctly classified in the metastatic or metastasis-free categories independently of hormone receptors and HER-2 status. Interestingly, c Kit was also a significant predictor of metastasis in node-negative tumours (2 out of 25 ranking, Po0.0001) and included in a six-marker signature of prognosis, correctly classifying 88.6% of the patients (Po0.0001). CONCLUSION: We concluded that, as assessed by quantitative immunohistochemistry, c Kit is an independent prognostic indicator that could also potentially serve as a target for specific therapy in breast carcinomas.

Disparate Impact of Butyroyloxymethyl Diethylphosphate (AN-7), a Histone Deacetylase Inhibitor, and Doxorubicin in Mice Bearing a Mammary Tumor

“…Overexpression of c-Kit in tumors points to the presence of cancer stem cells and predicts treatment resistance and poor outcomes. Therefore, disruption of c-Kit expression in c-Kit-driven tumors represents a promising therapeutic approach [46], [47]. In this study we demonstrated that both Dox and AN-7 substantially reduce Ki-67 and c-Kit expression in the tumor and AN-7+Dox abolish it, supporting the notion that the combination treatment can potentially benefit treatment-resistance and aggressive tumors.…”

c-kit (CD117) Expression in Human Tumors and its Prognostic Value: An Immunohistochemical Analysis

“…Concerning c-kit expression and prognosis the available data are controversial. In a recent study by Charpin et al [28] c-Kit expression in patients with breast carcinomas correlated with a poor patient outcome while a other study found that a loss of the c-kit expression is associated with an advanced stage of breast cancer [32].…”

“…While numerous clinical studies showed that cancer patients with either over-expression and/or mutations of c-Kit in their clinical samples have significantly poor prognosis, lower survival rates and show resistance to chemotherapy [25][26][27][28][29][30] other studies found no prognostic significance of c-kit expression [31][32][33].…”

Functional Activity of Ehrlich Carcinoma Cells After Treatment With Hybrid Nanocomplexes Containing Orthovanadates of Rare-Earth Elements, Cholesterol and Luminescent Dye

“…При цьому збільшувалася концентрація диференційованих CD44 + СD24 + -, CD44 -СD24 +та CD117 + -клітин порівняно з контролем. Деякими авторами підвищення рівня експресії CD117 вважається можливим тестом ефективності протипухлинної терапії [26]. У такому разі відзначене нами підвищення концентрації CD117 + -клітин удвічі порівняно з контролем на тлі пригнічення росту АКЕ на 58,24±3,45% може бути взаємозумовлюючим та свідчити про позитивний ефект цієї терапії (див.…”