Metaplastic Carcinoma of the Breast: p53 Analysis Identified the Same Point Mutation in the Three Histologic Components

Wang, Xiaojuan; Mori, Ichiro; Tang, Weihua; Yang, Qifeng; Nakamura, Misa; Nakamura, Yasushi; Sato, Misako; Sakurai, Takeo; Kakudo, Kennichi

doi:10.1038/modpathol.3880456

Cited by 50 publications

(32 citation statements)

References 12 publications

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“…44 However, in mixed mesenchymal breast tumors, reports on unequivocal mesenchymal lineages are numerous including chondroid and osteogenic differentiation. 45,46 That it really represents metaplasia (the divergent hypothesis) instead of a multiclonal tumor (the convergent hypothesis) has become increasingly clear based on the numerous studies of genetic markers in microdissected cells from within different compartments of the tissue. 46,47 The criteria in the present study used to categorize the cells as myofibroblastic were a fibroblastoid morphology, expression of the mesenchymal markers Thy-1 and vimentin, and most importantly the concomitant loss of keratins in some of the cells expressing ␣-sm actin.…”

Section: Discussionmentioning

confidence: 99%

Epithelial to Mesenchymal Transition in Human Breast Cancer Can Provide a Nonmalignant Stroma

Petersen¹,

Nielsen²,

Gudjonsson³

et al. 2003

The American Journal of Pathology

263

196

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A breast carcinoma biopsy showed cytochemical evidence of epithelial mesenchymal transition and an ␣-smooth muscle actin-positive stromal reaction. To study the lineage, and the nature of the cells in the stromal reaction, we derived a novel cell line, HBFL-1, from the explanted biopsy. HBFL-1 cells are immortal and exhibit a shared non-random X-chromosome inactivation pattern with the epithelial tumor of origin. Yet they closely resemble normal, finite-life-span fibroblasts by morphology, lack of tumor formation in nude mice, marker expression profile, protein pattern using two-dimensional gel electrophoresis and the ability to undergo myofibroblast conversion. HBFL-1 interacts reciprocally with tumor cells in collagen gel to induce activation of MMP2, leading to tumor-like behavior of epithelial colonies. In vivo, HBFL-1 cells resembled normal-derived myofibroblasts and conferred a significant 3.5-to 7-fold increase in MCF-7 tumor size in nude mice. However, that they were indeed not normal fibroblasts was revealed by residual keratin expression and formation of epithelial microfoci in a reconstituted basement membrane and in nude mice. We conclude that breast cancer can generate its own nonmalignant stroma and that one function for this is that of a reciprocal interac- Epithelial mesenchymal transition (EMT) was originally described as a normal developmental process. 1,2 Later, it was adopted as an explanation for mesenchymal conversion in a number of cultured epithelial cells. 3,4 In cancer, EMT generally depicts a more aggressive behavior of the tumor cells. 5,6 In breast cancer, EMT has been estimated to occur in as much as 18% of tumors in vivo. [7][8][9] Under these conditions EMT is defined as the occurrence of a variable proportion of tumor cells that express mesenchymal markers such as vimentin, tenascin and stromelysin-3. 7,10 In its most elaborate form, EMT-derived cells of mixed epithelial-mesenchymal breast tumors may be difficult to distinguish from resident normal stromal cells. 11 These tumors which are also referred to as carcinosarcomas or metaplastic carcinomas in particular offer an excellent opportunity to study the nature and the consequence of this subset of EMT. 5,6 Such studies, however, have been hampered by lack of representative cell lines most likely due to low frequency of overtly metaplastic carcinomas but also to difficulties in culturing breast cancer cells in general. In the present study we succeeded in isolating a mesenchymal-like cell line from a metaplastic human breast carcinoma. Clonality analysis revealed that the cell line and the epithelial tumor cells of origin had a common ancestor. Even though the cells were immortal and severely aneuploid, and exhibited a rudimentary epithelial phenotype in terms of keratin expression and formation of microfoci in Matrigel and in vivo, they nevertheless behaved remarkably like normal resident fibroblasts. In particular they responded to transforming growth factor-␤ (TGF-␤) by having ␣-smooth muscle actin (␣-sm actin) induced and t...

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Section: Discussionmentioning

confidence: 99%

Epithelial to Mesenchymal Transition in Human Breast Cancer Can Provide a Nonmalignant Stroma

Petersen¹,

Nielsen²,

Gudjonsson³

et al. 2003

The American Journal of Pathology

263

196

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“…These phenotypic alterations represent the expression of genotypic and molecular properties not present in normal mammary glandular cells, and in benign as well as some malignant conditions they are likely to be the result of de-repression of the normally coded molecular mechanisms responsible for the epithelial phenotype rather than histogenesis [11,12,13]. In support of this, some authors have demonstrated that basal-like BC may arise from luminal progenitor cells [14].…”

Section: Heterogeneity: Notions From Morphologymentioning

confidence: 74%

“…Mammary glandular cells show a high degree of phenotypic plasticity, which can be appreciated in both benign and malignant conditions [11,12,13]. These phenotypic alterations represent the expression of genotypic and molecular properties not present in normal mammary glandular cells, and in benign as well as some malignant conditions they are likely to be the result of de-repression of the normally coded molecular mechanisms responsible for the epithelial phenotype rather than histogenesis [11,12,13].…”

Section: Heterogeneity: Notions From Morphologymentioning

confidence: 99%

Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine

et al. 2018

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Breast cancer (BC) displays striking clinical, morphological, and behavioural diversity within a single tumour and between tumours. Currently, mounting evidence indicates that the morphological heterogeneity of BC reflects an underlying spectrum of genetic and epigenetic portraits that control BC behaviour. Further understanding of BC heterogeneity will have an impact, not only on the routine diagnostic practices but also on patients' management decisions. Phenomena like diagnostic inconsistencies and therapeutic resistance, both primary and acquired, could be attributed, at least in part, to tumour heterogeneity within the same cancer and between the primary disease and subsequent recurrences. From a practical standpoint, and to minimise the impact of BC intratumoral heterogeneity, pragmatic approaches for adequate tumour sampling have been suggested in translational biomarker discovery and validation research studies and in the clinical setting. Here, we provide a brief overview of BC heterogeneity, with an emphasis on the clinical consequences of intratumoral heterogeneity.

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“…The most explicable theory regarding the histogenesis of the metaplastic components is through transformation of myoepithelial cells. Wang et al 4 in their research consider that the tumor may have been derived from the same duct progenitor cells, and that these cells still remain multipotential after a p53 point mutation. The lineage of cells bound for luminal cells differentiate to ductal carcinoma, cells for basal cells differentiate to squamous carcinomatous element, and cells for myoepithelial cells differentiate to chondrosarcomatoid element.…”

Section: Discussionmentioning

confidence: 98%

“…The lineage of cells bound for luminal cells differentiate to ductal carcinoma, cells for basal cells differentiate to squamous carcinomatous element, and cells for myoepithelial cells differentiate to chondrosarcomatoid element. 4 Recent studies sug- gest that many cases of MC are of myoepithelial origin. Koker and Kleer suggested that p63, a sensitive and specific marker of myoepithelium, is expressed in most MCs of the breast.…”

Section: Discussionmentioning

confidence: 99%

Mixed metaplastic carcinoma of the breast associated with pregnancy: Diagnostic dilemmas in fine‐needle aspiration cytology

Σκάγιας

Vasou

Michalopoulou

et al. 2009

Diagnostic Cytopathology

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Metaplastic carcinoma of the breast represents a rare entity characterized by the simultaneous presence of ductal, squamous, and/or mesenchymal components in several proportions. There are limitations in fine-needle aspiration diagnosis due to its pathological heterogeneity. When it develops under pregnancy and lactation influence, the cytologic evaluation appears to be more difficult and accurate diagnosis often proves challenging. We describe a case of mixed metaplastic carcinoma with dominant areas of squamous metaplasia, sarcomatoid stroma with spindle cells, and a minor component of cartilaginous metaplasia. We notify our experience in diagnostic approach of this entity focusing on differential diagnosis.

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Metaplastic Carcinoma of the Breast: p53 Analysis Identified the Same Point Mutation in the Three Histologic Components

Cited by 50 publications

References 12 publications

Epithelial to Mesenchymal Transition in Human Breast Cancer Can Provide a Nonmalignant Stroma

Epithelial to Mesenchymal Transition in Human Breast Cancer Can Provide a Nonmalignant Stroma

Tumour Heterogeneity of Breast Cancer: From Morphology to Personalised Medicine

Mixed metaplastic carcinoma of the breast associated with pregnancy: Diagnostic dilemmas in fine‐needle aspiration cytology

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