KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favourable outcome. Mod Path

Department of Pathology, Institut Curie, Paris Cedex, France.
Modern Pathology (Impact Factor: 6.19). 01/2006; 18(12):1623-31. DOI: 10.1038/modpathol.3800483
Source: PubMed


Recent biological studies have classified breast carcinomas into HER2-overexpressing, estrogen receptor-positive/luminal, basal- and normal-like groups. According to this new biological classification, the objectives of our study were to assess the clinical, morphologic and immunophenotypic characteristics of adenoid cystic carcinoma of the breast in order to classify this subtype of breast carcinoma. A total of 18 cases of adenoid cystic carcinoma were identified from the Institut Curie files. Clinical information was available for 16 patients with a median follow-up of 6.5 years. Morphologically, all tumors were graded according to the system defined by Kleer and Oberman (histologic and nuclear grade). Immunophenotype was assessed with anti-ER, PR, HER-2, KIT, basal (CK5/6) and luminal cytokeratins (CK8/18) and p63 antibodies. One out of 18 tumors was nuclear grade 1 (16%), nine were nuclear grade 2 (50%) and eight were nuclear grade 3 (44%). All cases were estrogen receptor, progesterone receptor and HER-2 negative. Epithelial cells were strongly positive around glandular lumina with one or both cytokeratins, identifying the coexistence of CK5/6+ cells, CK5/6 and CK8/18+ cells, CK8/18+ cells and p63+ cells. All cases (100%) were also KIT positive. In all, 15 patients were treated by surgery. Nine of them received adjuvant radiotherapy. Follow-up was available for 16 patients. In all, 14 patients were alive. Two of them, initially treated by surgery only, presented a local recurrence. Two patients died (one of them treated by radiation therapy only died from her disease). Our study shows that adenoid cystic carcinoma of the breast is a special, estrogen receptor, progesterone receptor, HER-2 negative and highly KIT-positive, basal-like breast carcinoma, associated with an excellent prognosis. This highly specific immunophenotype could be useful to differentiate adenoid cystic carcinoma of the breast from other subtypes of breast carcinoma such as cribriform carcinoma.

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    • "Informed consents were not required, women were informed of the research use of their tissues, and did not declare any opposition for such researches. We performed IHC on these tissues, as described previously [27] and we determined after haematoxylin-eosin-safran (HES) staining that the tumors contained between 50–90% cancerous cells. We recorded ER and PR positive nuclear staining in accordance with standardized guidelines, using 10% as the cut-off for ER and PR positive cells. "
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    ABSTRACT: Triple-negative breast cancer (TNBC) represents a subgroup of breast cancers (BC) associated with the most aggressive clinical behavior. No targeted therapy is currently available for the treatment of patients with TNBC. In order to discover potential therapeutic targets, we searched for protein kinases that are overexpressed in human TNBC biopsies and whose silencing in TNBC cell lines causes cell death. A cohort including human BC biopsies obtained at Institut Curie as well as normal tissues has been analyzed at a gene-expression level. The data revealed that the human protein kinase monopolar spindle 1 (hMPS1), also known as TTK and involved in mitotic checkpoint, is specifically overexpressed in TNBC, compared to the other BC subgroups and healthy tissues. We confirmed by immunohistochemistry and reverse phase protein array that TNBC expressed higher levels of TTK protein compared to the other BC subgroups. We then determined the biological effects of TTK depletion by RNA interference, through analyses of tumorigenic capacity and cell viability in different human TNBC cell lines. We found that RNAi-mediated depletion of TTK in various TNBC cell lines severely compromised their viability and their ability to form colonies in an anchorage-independent manner. Moreover, we observed that TTK silencing led to an increase in H2AX phosphorylation, activation of caspases 3/7, sub-G1 cell population accumulation and high annexin V staining, as well as to a decrease in G1 phase cell population and an increased aneuploidy. Altogether, these data indicate that TTK depletion in TNBC cells induces apoptosis. These results point out TTK as a protein kinase overexpressed in TNBC that may represent an attractive therapeutic target specifically for this poor prognosis associated subgroup of breast cancer.
    PLoS ONE 05/2013; 8(5):e63712. DOI:10.1371/journal.pone.0063712 · 3.23 Impact Factor
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    • "Invasive ductal carcinoma was the most frequent histological subtype identified for the BLBCs in this study (76.59%), in accordance with the literature [7,10,27,28]. Although basal-like tumors were usually shown to have worse prognosis [4,16], several studies have also revealed that carcinomas known to have a good prognosis, such as invasive lobular carcinoma, adenoid cystic carcinoma and tubular carcinomas, may also show basal-like phenotype [29-31]. Most of the medullary carcinomas with their favourable outcome, also, had basal-like phenotype with both GEP and immunohistochemistry [32-34]. "
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    Diagnostic Pathology 10/2012; 7(1):145. DOI:10.1186/1746-1596-7-145 · 2.60 Impact Factor
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    • "The ETV6-NTRK3 and MYB-NFIB fusion genes have been recently described in secretory and adenoid cystic carcinomas, respectively.62,63 In Azoulay’s series (n = 18, median follow-up 6.5 years, one patient died of disease) adenoid cystic TNBCs had excellent outcomes even in the absence of adjuvant chemotherapy, and on reviewing the literature (n = 219 adenoid cystic TNBC cases), they found a 3% breast cancer specific death rate, although information on adjuvant treatment was lacking.64 Despite the histological features of classical medullary carcinomas (ie, highly proliferative, poorly differentiated carcinomas), these tumors frequently carry a good prognosis. "
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