Quantitative immunohistochemical expression of c Kit in breast carcinomas is predictive of patients' outcome.
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=0.02 and particularly in node-negative cases (P=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=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, P<0.0001) and included in a six-marker signature of prognosis, correctly classifying 88.6% of the patients (P<0.0001).


CONCLUSIONS
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.
Charpin
C
C
Department of Pathology, Hôpital Nord and Université de la Méditerranée (Aix Marseille II), Marseille, France. colette.charpin@ap-hm.fr
Giusiano
S
S
Charfi
S
S
Secq
V
V
Carpentier
S
S
Andrac
L
L
Lavaut
M-N
MN
Allasia
C
C
Bonnier
P
P
Garcia
S
S
D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D003720:Densitometry / Q000379:methods; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D016015:Logistic Models; D008207:Lymphatic Metastasis; D046228:Microarray Analysis / Q000379:methods; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D011237:Predictive Value of Tests; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D012372:ROC Curve
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit