Basal-like Breast Carcinomas: Identification by the Expression of Basal Cytokeratins, P-cadherin, P63 and EGFR (original) (raw)
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Clinical Cancer Research, 2004
Purpose: Expression profiling studies classified breast carcinomas into estrogen receptor (ER)؉/luminal, normal breast-like, HER2 overexpressing, and basal-like groups, with the latter two associated with poor outcomes. Currently, there exist clinical assays that identify ER؉/luminal and HER2-overexpressing tumors, and we sought to develop a clinical assay for breast basal-like tumors.
Basal-like breast carcinoma: a phenotypically distinct entity
Archives of pathology & laboratory medicine, 2010
Gene microarray profiling of human breast carcinomas has recently categorized invasive breast carcinomas into 5 distinct subtypes; luminal A, luminal B, normal breastlike, human epithelial growth factor receptor 2 (HER2) overexpressing, and basal-like. Basal-like breast carcinomas are characterized by high expression of basal cytokeratins; low or absent expression of estrogen receptor, progesterone receptor, and HER2/neu; and expression of epidermal growth factor receptor (EGFR) and/or c-kit, and they are frequently associated with breast cancer 1 (BRCA1) mutations and poor clinical outcome. Recent studies have begun to provide insights into the molecular genetics, biology, morphology, and clinical outcome of this subtype of breast carcinoma. We reviewed the literature related to basal-like breast carcinomas to better understand this clinically significant subtype of breast carcinoma.
Relationship of P-cadherin expression to basal phenotype of breast carcinoma
Polish journal of pathology: official journal of the Polish Society of Pathologists
P-cadherin (P-CD) is a molecule expressed mainly by basal cells involved in cell adhesion. We evaluated expression of P-CD in operable breast carcinomas and its relationship with immunohistochemical markers of the basal-like phenotype and with clinical outcome. Expression of P-CD was analyzed by immunohistochemistry in 194 tissue specimens of invasive operable ductal breast cancer. 112 cases (57.7%) were identified as being P-CD-positive. P-CD-positive tumors usually lacked steroid receptors (p = 0.042), expressed basal type cytokeratins (p = 0.001), and were positive for cyclin E (p = 0.039). In a univariate analysis of cancer-specific survival with a median follow-up period of 58 months, P-CD expression was not associated with prognosis (5-year survival rate for positive vs. negative patients 67.0 vs. 77.0%, log rank p = 0.121). P-CD may be regarded as an additional immunohistochemical marker of basal-like breast carcinomas. However, P-CD expression is not an adverse prognostic fa...
Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma
2005
Microarray profiling of invasive breast carcinomas has identified five distinct subtypes of tumors (luminal A, luminal B, normal breast-like, HER2 overexpressing, and basal-like) that are associated with different clinical outcomes. The basal-like subtype is associated with poor clinical outcomes and is the subtype observed in BRCA1-related breast cancers. The aim of this study was to characterize the histologic and immunophenotypic properties of breast basal-like carcinomas that were first positively identified using DNA microarray analysis. Detailed histologic review was performed on 56 tumors with known microarray profiles (23 basal-like, 23 luminal, and 12 HER2 þ). Immunohistochemistry for estrogen receptor (ER), HER2, EGFR, smooth muscle actin (SMA), p63, CD10, cytokeratin 5/6, cytokeratin 8/18, and vimentin was performed on 18 basal-like, 16 luminal, and 12 HER2 þ tumors. The basal-like tumors were grade 3 ductal/NOS (21/23) or metaplastic (2/23) carcinomas that frequently showed geographic necrosis (17/23), a pushing border of invasion (14/23), and a stromal lymphocytic response (13/23). Most basal-like tumors showed immunoreactivity for vimentin (17/18), luminal cytokeratin 8/18 (15/18), EGFR (13/18), and cytokeratin 5/6 (11/18), while positivity for the myoepithelial markers SMA (4/18), p63 (4/18) and CD10 (2/18) was infrequent. All basal-like tumors tested were ERÀ and HER2À. Morphologic features significantly associated with the basal-like subtype included markedly elevated mitotic count (Po0.0001), geographic tumor necrosis (P ¼ 0.0003), pushing margin of invasion (P ¼ 0.0001), and stromal lymphocytic response (P ¼ 0.01). The most consistent immunophenotype seen in the basal-like tumors was negativity for ER and HER2, and positivity for vimentin, EGFR, cytokeratin 8/18, and cytokeratin 5/6. The infrequent expression of myoepithelial markers in basal-like carcinomas does not support a direct myoepithelial cell derivation of these tumors. These findings should further assist in the identification of basal-like carcinomas in clinical specimens, facilitating treatment and epidemiologic studies of this tumor subtype.
Basic and Applied Pathology, 2010
Background and aim: DNA expression profiling studies of breast cancer have identified subtypes including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) overexpression, and basal-like type. Among them, the basallike type was associated with poor outcome. The purpose of this study was to classify breast carcinoma by immunohistochemistry and evaluate its characteristic histopathologic features. Methods: One hundred and four cases of resected infiltrating ductal carcinoma were immunostained for estrogen receptor, HER2, cytokeratin 5/6 and p63 to classification, and basal-like subtype were evaluated for its histopathologic characteristics. Results: The prevalence of subtypes was luminal A 48.1%, luminal B 24.0%, HER2 overexpression 11.5%, normal breast-like 4.8%, and basal-like 11.5%. There was significant correlation between the basal-like type and histologic grade. And it was significantly associated with several morphological features including expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration. Conclusions: The results of this study showed that the basal-like type occupied 11.5% of infiltrating ductal carcinoma and was associated with expanding growth pattern, presence of tumor necrosis and peritumoral lymphocytic infiltration.
Indian Journal of Medical Sciences, 2009
BACKGROUND: Normal breast ducts contain at least 3 types of epithelial cells: luminal (glandular) cells, basal/myoepithelial cells and stem cells. Myoepithelial and luminal epithelia can be distinguished by their different cytokeratin expression patterns. The aim of this study is to evaluate the expression of some prognostic biomarkers (ER, PR and HER2), as well as histological grading and lymph node status in cytokeratin-based groups of breast cancer. OBJECTIVE: To evaluate the correlation between expression of basal and luminal markers and hormonal receptors, HER2/neu, age, grade and lymph node status in breast-invasive ductal carcinoma. MATERIALS AND METHODS: Sixtyseven formalin-fixed and paraffin-embedded breast cancer specimens (of invasive ductal carcinoma, 'NOS' type) which had already been studied for ER, PR and HER2/neu were selected. Data concerning age, tumor grade and lymph node status were also obtained from archives. Expression of basal (CK5/6) and luminal (CK7) cytokeratins was detected by immunohistochemistry. Stained sections were classified according to the intensity of staining and the percentage of stained cells. RESULTS: We categorized the cases into 3 distinct phenotype groups: pure luminal, basal phenotype and null. Pure basal, mixed basal and luminal groups were classified as expressing a basal phenotype. There was a significant difference in the ER and/or PR expression between those 3 groups and a significant association between ER and/or PR negativity and basal phenotype expression. There was no significant difference in HER2/neu expression, age of the patients, tumor grade and lymph node status between the 3 cytokeratin-based groups and no significant association between lymph node status and basal phenotype expression. CONCLUSION: We found that to gain a real association between basal phenotype and prognostic markers, we should use a cocktail or a panel of different biomarkers to correctly determine basal-like phenotype of breast cancers. This approach guarantees more concordance with gene expression-based studies.
Metaplastic breast carcinomas are basal-like tumours
Histopathology, 2006
Aims : Recently, an immunohistochemical panel comprising antibodies against HER2, oestrogen receptor (ER), epidermal growth factor receptor (EGFR) and cytokeratin (CK) 5/6 was reported to identify basal-like breast carcinomas, as defined by cDNA microarrays. Our aim was to analyse a series of metaplastic breast carcinomas (MBCs) using this panel plus two other basal markers (CK14 and p63) and progesterone receptor (PR), to define how frequently MBCs show a basal-like immunophenotype.Methods and results : Sixty-five cases were retrieved from the pathology archives of the authors' institutions and reviewed by three of the authors. Immunohistochemistry with antibodies for HER2, ER, EGFR, CK5/6, CK14 and p63 was performed according to standard methods. All but six cases (91%) showed the typical immunoprofile of basal-like tumours (ER– and HER2–, EGFR+ and/or CK5/6+). When CK14 and p63 were added to the panel, two additional cases could be classified as basal-like. The majority of MBCs lacked PR, except 4/19 (21%) carcinomas with squamous metaplasia.Conclusions : Our results demonstrate that MBCs show a basal-like phenotype, regardless of the type of metaplastic elements. Moreover, as these neoplasms frequently overexpress EGFR (57%), patients with MBC may benefit from treatment with anti-EGFR drugs.
The Breast Journal, 2012
n Abstract: Basal-cell phenotype breast carcinoma has been associated with high-grade and metaplastic morphology, expression of basal-type cytokeratins, uniform negativity for ER and HER2, and decreased overall survival. Breast cancers occurring in young women are usually T2 disease at presentation, high-grade and of poor prognosis. We compared two groups of breast cancers, (a) ER-, PR-, HER2-(triple negative) [TNBrCa] and (b) non-triple negative breast cancers (non-TNBrCa) occurring in women under 35, using tissue microarray technology to characterize expression of the basal ⁄ myoepithelial cytokeratins (CK5 ⁄ 6, CK7, and CK14), luminal cytokeratins (CK8, CK18, and CK19), EGFR, p-cadherin, c-kit, p63, and p53. We also sought to identify characteristic histomorphologic features indicative of basal-like phenotype. The triple negative group showed preferential staining versus the age <35 group for CK5 ⁄ 6 (22% versus 4% p = 0.05), CK14 (44% versus 15%, p = 0.013), EGFR (83% versus 24%, p < 0.0001) and c-kit (19% versus 0% p = 0.026). Conversely, non-TNBrCa in women younger than 35 demonstrated increased expression of the luminal CK8 (92% versus 60%) compared with the triple negative patients (p = 0.006). The TNBrCa have characteristic histologic features including higher tumor grade, pushing tumor border, geographic necrosis, syncytial growth pattern, brisk mitotic activity, lack of ⁄ minimal in situ component, medullary-like and metaplastic differentiation. Invasive carcinomas in women younger than 35 usually have an associated in situ component, prominent nucleoli, central acellular fibrotic zone, and infiltrative tumor border. Triple negativity for ER ⁄ PR ⁄ HER2 coupled with EGFR, c-kit, and basal ⁄ myoepithelial cytokeratins (CK5 ⁄ 6, CK14) expression, and distinctive histomorphologic features predict morphology consistent with basal-cell phenotype. n