title: C-kit expression in high-risk breast cancer subgroup treated with high-dose or conventional dose-dense chemotherapy.
abstract: The proto-oncogene c-kit is known to be expressed in poorly differentiated breast cancer. In this study, we retrospectively evaluated the prognostic and predictive impact of c-kit in a high risk subgroup of breast cancer patients (>9 axillary node metastases) who received high-dose (HDCT) or dose-dense (DDCT) conventional chemotherapy and correlated these findings with the expression of the basal-type markers CK5 and CK 17, estrogen (ER) and progesterone (PR) receptor, Her-2/neu and MIB 1. C-kit, CK5, CK17, ER, PR, Her-2/neu and MIBI expression was evaluated immunohistochemically using tissue microarrays containing breast cancer samples from 236 patients who were randomized to the WSG AM01 trial (median follow-up of 60 months). There was a significant overall survival (OS) benefit for patients receiving HDCT compared to DDCT (p = 0.027). C-KIT expression was found in 12 % of all breast cancers and correlated with a poorer OS in multivariate analysis (p = 0.051). Furthermore, c-kit correlated with high grade (p = 0.019), CK5- and CK17-positivity (p <0.0001 and p = 0.001, respectively) and ER- and PR-negativity (p = 0.04 and p = 0.008, respectively). In contrast to CK5 and CK17, patients with c-kit positive breast cancers revealed no benefit from high-dose chemotherapy. These findings underline that c-kit expression represents an independent negative prognostic marker in high-risk breast cancer. Correlation with CK5 +/CK17+ and ER-/PR-suggests that c-kit positive carcinomas are at least partly of basal-type.
authors.affiliation: Institut für Pathologie, Universität Düsseldorf.
authors.forename: R
authors.initials: R
authors.lastname: Diallo
authors.forename: E
authors.initials: E
authors.lastname: Ting
authors.forename: O
authors.initials: O
authors.lastname: Gluz
authors.forename: A
authors.initials: A
authors.lastname: Herr
authors.forename: G
authors.initials: G
authors.lastname: Schütt
authors.forename: H
authors.initials: H
authors.lastname: Geddert
authors.forename: S
authors.initials: S
authors.lastname: Mohrmann
authors.forename: H E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: U
authors.initials: U
authors.lastname: Nitz
authors.forename: C
authors.initials: C
authors.lastname: Poremba
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D002986:Clinical Trials as Topic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008207:Lymphatic Metastasis; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics*; D012189:Retrospective Studies; D019089:Stem Cell Factor / Q000235:genetics*; D015996:Survival Rate; D017741:Survivors
chemical_list: D000970:Antineoplastic Agents; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019089:Stem Cell Factor; D019009:Proto-Oncogene Proteins c-kit