Large, Central Acellular Zones Indicating Myoepithelial Tumor Differentiation in High-Grade Invasive Ductal Carcinomas as Markers of Predisposition to Lung and Brain Metastases

Tsuda, Hitoshi; Takarabe, Teruko; Hasegawa, Fumio; Fukutomi, Takashi; Hirohashi, Setsuo

doi:10.1097/00000478-200002000-00005

Cited by 191 publications

(188 citation statements)

References 7 publications

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“…Such tumours may be worth identifying separately as they probably need a different therapeutic approach. The 'high-grade ductal carcinoma with extensive central scar' (ring carcinoma), may be one of these lesions that is becoming gradually more defined morphologically and clinically, 3,[32][33][34] in spite of the absence of an agreed name. Further analysis of more cases may lead to the identification of other distinct subtypes.…”

Section: Discussionmentioning

confidence: 99%

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma

Kesse‐Adu

Shousha

2004

Modern Pathology

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Around 20% of invasive breast carcinoma are oestrogen receptor alpha (ER) negative. Theoretically, this negativity could be either due to the result of downregulation of ER expression in the tumour cells, or the result of the tumour being derived from or differentiating towards cells which normally lack that expression. Normal basal, including myoepithelial, cells of the breast are ERnegative. CD10, smooth muscle actin and S100 are markers of these basal cells that can be used for their demonstration in routinely processed sections. This study was aimed at comparing the incidence of positivity for three myoepithelial markers in ER-negative and ER-positive invasive breast carcinoma. We have examined sections of 117 cases of breast carcinoma, including 77 ER-negative and 40 ER-positive cases, for the expression of CD10, smooth muscle actin and S100, using the avidin-biotin complex immunoperoxidase technique. A tumour was considered positive if more than 10% of the tumour cells were positively stained. In all, 36 (47%) ER-negative tumours were positive for one or more of these myoepithelial markers. The percentage of positively stained tumour cells varied between 30 and 100%. Of the 40 ER-positive tumours, only three (8%) were positive; two for S100 and one for actin, with none being positive for CD10. If cases stained only with S100 are excluded, as some of these may represent luminal differentiation, definite myoepithelial differentiation seems to be present in 29% (22/77) of ER-negative tumours as compared with 2.5% (1/40) of ER-positive tumours; a difference which is highly significant (Po0.001). It is suggested that at least 29% of ER-negative invasive breast carcinomas may be derived from or differentiating along the direction of basal nonconventional luminal epithelial breast cells that normally lack the expression of ER but totally or partially express various myoepithelial markers. Such tumours might need a different therapeutic approach.

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Section: Discussionmentioning

confidence: 99%

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma

Kesse‐Adu

Shousha

2004

Modern Pathology

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“…114 However, when compared with either ERÀ non-basal-like cancers 72 or grade-matched non-basal-like cancers, 42 carcinomas with a basal-like phenotype are not associated with a poorer outcome in some studies, whereas a more adverse prognosis is observed in others. 19,116 The pattern of metastatic spread of tumors with a basal-like phenotype seems to be different from that of non-basal-like cancers: they are reported to less frequently disseminate to axillary nodes and bones 42,117 and to favor a hematogenous spread, 42,[117][118][119] with a peculiar proclivity to develop metastatic deposits in the brain and lungs. 120 It should be noted that patients with triple-negative and basal-like cancers tend to develop adverse events and die due to disease within the first 5-8 years after diagnosis.…”

Section: Clinical Behavior Of Basal-like and Triple-negative Breast Cmentioning

confidence: 99%

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

et al. 2011

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Breast cancer is a heterogeneous disease encompassing a variety of entities with distinct morphological features and clinical behaviors. Although morphology is often associated with the pattern of molecular aberrations in breast cancers, it is also clear that tumors of the same histological type show remarkably different clinical behavior. This is particularly true for 'basal-like cancer', which is an entity defined using gene expression analysis. The purpose of this article was to review the current state of knowledge of basal-like breast cancers, to discuss the relationship between basal-like and triple-negative breast cancers, and to clarify practical implications of these diagnoses for pathologists and oncologists.

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“…12 Studies have employed basal/myoepithelial cytokeratins and other markers to identify a subset of ER-and HER2-negative breast carcinomas that are associated with a poor prognosis, further supporting the idea that a basal-like phenotype exists. [13][14][15][16][17][18] The prevalence and poor prognosis of basal-like breast carcinomas have been validated immunohistochemically; in a 564-case tissue microarray, van de Rijn et al 12 demonstrated that 16% of tumors stained positive for cytokeratin 5/6 or cytokeratin 17, and that basal cytokeratin expression was associated with a poor prognosis. Abd El-Rehim evaluated 1944 cases of invasive breast carcinoma and found that approximately 18% of tumors show basal cytokeratin immunoreactivity, and again, these tumors showed a poor prognosis.…”

mentioning

confidence: 99%

“…Abd El-Rehim evaluated 1944 cases of invasive breast carcinoma and found that approximately 18% of tumors show basal cytokeratin immunoreactivity, and again, these tumors showed a poor prognosis. 14 Tsuda et al 17,18 described myoepithelial differentiation in a group of high-grade invasive ductal carcinomas showing a large, central acellular zone. These tumors showed aggressive behavior with increased risk of brain and lung metastasis.…”

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confidence: 99%

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

et al. 2006

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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.

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Large, Central Acellular Zones Indicating Myoepithelial Tumor Differentiation in High-Grade Invasive Ductal Carcinomas as Markers of Predisposition to Lung and Brain Metastases

Cited by 191 publications

References 7 publications

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma

Myoepithelial markers are expressed in at least 29% of oestrogen receptor negative invasive breast carcinoma

Basal-like and triple-negative breast cancers: a critical review with an emphasis on the implications for pathologists and oncologists

Phenotypic evaluation of the basal-like subtype of invasive breast carcinoma

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