title: C-KIT expression in ductal carcinoma in situ of the breast: co-expression with HER-2/neu.
abstract: The proto-oncogene c-KIT (CD117) is highly expressed in normal breast epithelium and is decreased in invasive breast cancer. In this study, we analyzed the protein expression and the mutational status of c-KIT in ductal carcinoma in situ (DCIS) of the breast and correlated these findings with nuclear grade, architectural pattern, and expression of HER-2, estrogen receptor (ER)-alpha, and progesterone receptor (PR). C-KIT, HER-2, ER, and PR expression were analyzed immunohistochemically in 106 cases of paraffin-embedded DCIS (85 pure DCIS and 21 DCIS with concurrent carcinoma). Direct sequencing of exons 9 and 11 of the c-KIT gene was performed to analyze the hot spot mutational regions in representative cases. C-KIT expression was found in 55 (52.8%) of all DCIS, correlating with high nuclear grade (P < .0001), comedonecrosis (P < .0001), and solid growth pattern (P = .001). Furthermore, c-KIT expression was strongly associated with HER-2 positivity (P < .0001) and was significantly lower in ER- or PR-positive cases (P = .001 and P = .006, respectively). C-KIT expression alone or co-expression with HER-2 in pure DCIS did not differ significantly from DCIS with invasive component (P = .09). Mutational analysis in 6 c-KIT-positive DCIS revealed no activating mutations in exons 9 or 11. Our findings suggest that the expression of c-KIT protein might define a subset of poorly differentiated, HER-2-positive DCIS with decreased expression of steroid hormone receptors, comedonecrosis, and a solid growth pattern. The implications of c-KIT and HER-2 co-expression for breast carcinogenesis should be further evaluated.
authors.affiliation: Institute of Pathology, Heinrich-Heine-University of Düsseldorf, Germany.
authors.forename: Raihanatou
authors.initials: R
authors.lastname: Diallo
authors.forename: Achim
authors.initials: A
authors.lastname: Rody
authors.forename: Christian
authors.initials: C
authors.lastname: Jackisch
authors.forename: Evelyn
authors.initials: E
authors.lastname: Ting
authors.forename: Karl-Ludwig
authors.initials: KL
authors.lastname: Schaefer
authors.forename: Stefan
authors.initials: S
authors.lastname: Kissler
authors.forename: Thomas
authors.initials: T
authors.lastname: Karn
authors.forename: Helene
authors.initials: H
authors.lastname: Geddert
authors.forename: Knut
authors.initials: K
authors.lastname: Engels
authors.forename: Manfred
authors.initials: M
authors.lastname: Kaufmann
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Shroyer
authors.forename: Christopher
authors.initials: C
authors.lastname: Poremba
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000145:classification / Q000378:metabolism*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit / Q000096:biosynthesis*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis
chemical_list: D000090063:Proto-Oncogene Mas; D019009:Proto-Oncogene Proteins c-kit; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C000715470:MAS1 protein, human