Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions

Mardekian, Stacey K.; Bombonati, Alessandro; Palazzo, Juan

doi:10.1016/j.humpath.2015.11.003

Cited by 50 publications

(44 citation statements)

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“…The currently available therapies are indicated based on the morphological and genetic characteristics of the tumor (1,2). Novel molecular techniques of gene expression profiling and microarray analysis enabled the identification of distinct invasive breast cancer (IBC) molecular subtypes, such as luminal A, luminal B, tumors enriched with human epidermal growth factor receptor 2 (HER-2) and triple-negative tumors.…”

Section: Introductionmentioning

confidence: 99%

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

et al. 2018

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Molecular phenotyping and tissue microarray (TMA) studies have identified distinct invasive breast carcinoma subtypes: Luminal A, luminal B, enriched with overexpressed human epidermal growth factor receptor 2 (HER-2) and triple-negative, i.e., negative for HER-2, as well as for estrogen and progesterone receptor (ER and PR, respectively) expression. These subtypes are useful in clinical management, since they bear distinct prognoses and predictive responses to targeted therapy. However, although molecular profiling provides important prognostic indicators, breast cancer risk stratification remains a challenge in triple-negative cases. What is referred to as claudin-low subtype was identified as a triple-negative subset that is associated with more aggressive tumor behavior and worse prognosis. However, the immunohistochemical expression of claudins has not yet been standardized. Our objective was to verify whether the immunoexpression of claudins 4 and 7 (the main claudins specifically expressed in human breast tissue) in TMA is associated with survival and prognosis in luminal A, HER-2 and triple-negative molecular subtypes. In this diagnostic study, we investigated ER/PR receptor status, HER-2, claudin 4 and 7 expression and stem cell CD44/24 profiles, and verified the association with prognosis and survival outcomes in 803 invasive breast carcinoma cases arranged in four TMAs. Among these, 503 (62.6%) were positive for claudin 4 and 369 (46.0%) for claudin 7. Claudin 4 exhibited the lowest expression in luminal A and triple-negative subtypes, and the highest frequency of expression in HER-2-enriched subtypes, whereas claudin 7 staining was not associated with any subtype. The stem cell phenotype was not associated with subgroups or claudins 4 and 7. Claudin immunoexpression profile was not able to distinguish between patients with better or worse prognosis, and it was not correlated to triple-negative cases. Therefore, it may be concluded that the immunoexpression of claudins 4 and 7, individually or within the usual immunohistochemical context (ER, PR and HER-2), does not provide additional prognostic information on breast cancer subtypes.

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Section: Introductionmentioning

confidence: 99%

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

et al. 2018

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“…Since the introduction of mammography screening, ductal carcinoma in situ (DCIS) constitutes about 20‐25% of newly diagnosed cases of breast cancer in industrialized countries and, although DCIS is a non‐obligate precursor, it may constitute a crucial step in the progression toward invasive ductal carcinoma (IDC) . The progression of DCIS to IDC is a very complex biological phenomenon and recent studies indicate that cells in DCIS lesions likely harbor molecular alterations that render them prone to the acquisition of invasive capability …”

Section: Introductionmentioning

confidence: 99%

Ectopic expression of PLC‐β2 in non‐invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR‐146a

Bertagnolo

Grassilli

Volinia

et al. 2019

Molecular Carcinogenesis

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Cells in non‐invasive breast lesions are widely believed to possess molecular alterations that render them either susceptible or refractory to the acquisition of invasive capability. One such alteration could be the ectopic expression of the β2 isoform of phosphoinositide‐dependent phospholipase C (PLC‐β2), known to counteract the effects of hypoxia in low‐invasive breast tumor‐derived cells. Here, we studied the correlation between PLC‐β2 levels and the propensity of non‐invasive breast tumor cells to acquire malignant features. Using archival FFPE samples and DCIS‐derived cells, we demonstrate that PLC‐β2 is up‐regulated in DCIS and that its forced down‐modulation induces an epithelial‐to‐mesenchymal shift, expression of the cancer stem cell marker CD133, and the acquisition of invasive properties. The ectopic expression of PLC‐β2 in non‐transformed and DCIS‐derived cells is, to some extent, dependent on the de‐regulation of miR‐146a, a tumor suppressor miRNA in invasive breast cancer. Interestingly, an inverse relationship between the two molecules, indicative of a role of miR‐146a in targeting PLC‐β2, was not detected in primary DCIS from patients who developed a second invasive breast neoplasia. This suggests that alterations of the PLC‐β2/miR‐146a relationship in DCIS may constitute a molecular risk factor for the appearance of new breast lesions. Since neither traditional classification systems nor molecular characterizations are able to predict the malignant potential of DCIS, as is possible for invasive ductal carcinoma (IDC), we propose that the assessment of the PLC‐β2/miR‐146a levels at diagnosis could be beneficial for identifying whether DCIS patients may have either a low or high propensity for invasive recurrence.

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“…This type of cancer is regarded as a transitional stage between the normal breast tissue and invasive cancer. It is characterised with a significant diversity of the morphological, immunochemical, molecular and clinical picture [1]. Depending on the tissue architecture, DCIS can be defined as solid, cribriform, papillary and micropapillary; whilst depending on the malignancy grade, as: poorly-, moderately-and highly differentiated and -depending on the presence of the comedo type necrosis -as comedo type carcinoma (with a more aggressive clinical course) and non-comedo type carcinoma.…”

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confidence: 99%

“…The basic arguments for the treatment of ductal carcinoma in situ in the same way as early invasive cancer comprise: -unknown natural history of untreated DCIS [16]; -high risk of undervaluation of the invasive component in the core-needle biopsy [10,[16][17][18]; -increase of recurrence risk with the progress of time [3,[19][20][21]; -lack of verified separators of the groups with the risk of adverse course of the disease [1,2,20]; -the results of the clinical studies confirming the justification of combined local treatment [22][23][24][25][26]; -and the proof that the clinical course of DCIS is the same as early invasive breast cancer [27,28]; -the lack of clinical studies which could justify a limitation of the treatment scope [28][29][30]. Given the fact that a large share of ductal carcinoma in situ is diagnosed as a small lesion seen only in a mammography image, and then treated with a mammotomy biopsy, a substantial part of DCIS is resected during this procedure.…”

mentioning

confidence: 99%

“…For the time being the studies concentrate on the analysis of epigenetic modifications such as DNA methylation and the changes within miRNA, which play a significant role in genetic disorders. Additionally, the tumour increase and invasion are facilitated by a distorted tumour microenvironment, whose fibroblasts and macrophages excrete growth factors and angiogenesis stimulating factors [1]. Another group of molecular studies concern the relationships of the expression of selected biomarkers and the prognoses, where the triple-positive DCIS (p16, COX-2, Ki67) is significantly related to a higher risk of the occurrence of invasive breast cancer [31].…”

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confidence: 99%

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Should local treatment of breast ductal carcinoma in situ be the same as the treatment of early invasive breast cancer

Grodecka-Gazdecka¹

2017

Nowotwory. Journal of Oncology

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Should local treatment of breast ductal carcinoma in situ be the same as the treatment of early invasive breast cancer Sylwia Grodecka-GazdeckaHeterogenicity of breast ductal carcinoma in situ gives rise to opposing proposals concerning its treatment -ranging from attempts to recommend the watch and wait strategy in low risk forms ending with the currently binding standards of treatment of DCIS in the way identical as early invasive cancer in the high risk. Arguments for the treatment of ductal carcinoma in situ in the same way as patients with early invasive cancer have been presented. These arguments comprise: unknown natural history of untreated DCIS, high risk of undervaluation of the invasive component in the core-needle biopsy, the increase of recurrence risk with the progress of time, lack of verified separators of the groups with the risk of adverse course of the disease, the results of the clinical studies confirming the justification of combined local treatment and the proof that the clinical course of DCIS is the same as early invasive breast cancer, and, first and foremost, the fact that there are no clinical studies which could justify a limitation of the treatment scope.NOWOTWORY J Oncol 2017; 67, 1: 74-78

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Ductal carcinoma in situ of the breast: the importance of morphologic and molecular interactions

Cited by 50 publications

References 91 publications

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

Immunoexpression of claudins 4 and 7 among invasive breast carcinoma subtypes: A large diagnostic study using tissue microarray

Ectopic expression of PLC‐β2 in non‐invasive breast tumor cells plays a protective role against malignant progression and is correlated with the deregulation of miR‐146a

Should local treatment of breast ductal carcinoma in situ be the same as the treatment of early invasive breast cancer

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