Ductal carcinoma in situ associated with triple negative invasive breast cancer: evidence for a precursor–product relationship

Thike, Aye Aye; Iqbal, Jabed; Cheok, Poh Yian; Tse, Gary M.; Tan, Puay Hoon

doi:10.1136/jclinpath-2012-201428

Cited by 23 publications

(15 citation statements)

References 41 publications

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“…According to Zhou et al, the risk of recurrence for triple-negative DCIS was significantly higher amongst all the molecular subtypes after a follow-up period of 10 years [47]. Triplenegative DCIS has been found to be associated with triplenegative invasive breast cancer, and is likely to be the precursor lesion [19]. The same study found that 97.9 % of DCIS associated with triple-negative invasive breast cancer were also triple negative, suggesting that its higher occurrence amongst our cases of symptomatic DCIS may implicate aggressive behaviour of invasive recurrences.…”

Section: Discussionmentioning

confidence: 99%

“…This was followed by incubation in an oven overnight at 80°C to increase adhesion of the sections to the slides. Immunohistochemistry (IHC) was performed using antibodies to oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR), and cytokeratins (CK14 and 34bE12) according to previously published protocol [19]. Details of the antibodies, dilution factors, and antigen retrieval methods are provided in Table 1.…”

Section: Immunohistochemistrymentioning

confidence: 99%

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Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients

Koh

Lim

Thike

et al. 2015

Breast Cancer Res Treat

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Breast cancer is the most common malignancy in Singapore women. Ductal carcinoma in situ (DCIS) is the putative, non-obligate precursor of the majority of invasive breast cancers. The efficacy of the Singapore breast-screening pilot project in detecting early stage breast cancer led to the launch of a national breast-screening programme, BreastScreen Singapore (BSS), in January 2002. In this study, we compared clinicopathological and immunohistochemical characteristics, as well as clinical outcomes, between screen-detected and symptomatic DCIS. The study cohort comprised 1202 cases of DCIS diagnosed at Singapore General Hospital from 1994 to 2010. Comparison of clinicopathological parameters, immunohistochemical results of ER, PR, HER2, CK14, EGFR, and 34βE12, and clinical outcomes was carried out between the 2 groups. Amongst 1202 cases, 610 (50.7%) were screen-detected and 592 (49.3%) were symptomatic DCIS. Screen-detected cases were smaller in size (P < 0.001), of lower nuclear grade (P = 0.004), and more frequently expressed ER (P < 0.001). Luminal A phenotype was more frequently observed in screen-detected DCIS, while triple-negative and HER2 phenotypes were more common in symptomatic DCIS (P < 0.001). The basal-like phenotype was also more frequent in symptomatic DCIS (P = 0.041). Mean and median follow-up was 99.7 and 97.8 months, respectively, with a maximum follow-up of 246.0 months. More symptomatic patients developed invasive recurrences compared to screen-detected patients (P = 0.001). A trend for better disease-free survival was observed in screen-detected patients (P = 0.076). Patients who were screen-detected experienced better overall survival than those with symptomatic DCIS (P = 0.007). Our data indicate a more favourable outcome of screen-detected DCIS patients confirming the role of BSS in early identification of this curable disease.

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Section: Discussionmentioning

confidence: 99%

Section: Immunohistochemistrymentioning

confidence: 99%

Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients

Koh

Lim

Thike

et al. 2015

Breast Cancer Res Treat

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“…TMA sections (4 µm) were subjected to IHC using antibodies shown in table 1, according to published protocols 33. IHC for ER, PR and HER2 was conducted to reconfirm triple negativity; epidermal growth factor receptor (EGFR) and cytokeratins (CK14 and high molecular weight clone 34βE12) were used to detect basal-like phenotype 2.…”

Section: Methodsmentioning

confidence: 99%

Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women

et al. 2017

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BackgroundTriple-negative breast cancers (TNBCs) are defined by their lack of oestrogen receptor, progesterone receptor and epidermal growth factor receptor 2. Although heterogeneous, the majority are aggressive and treatment options are limited. Caveolin acts as tumour suppressor or promoter depending on the cancer type.AimIn this study, we aimed to determine if the expression levels of the candidate biomarker caveolin-1 on stromal or tumour cells were associated with clinicopathological parameters and disease outcomes in TNBCs from an ethnically diverse cohort of Asian women.MethodsTumour specimens from 699 women with TNBC were subjected to immunohistochemical analysis of the frequency and intensity of caveolin-1 expression in tumour and stromal cells. A subset of 141 tumour samples also underwent Nanostring measurement of CAV1 mRNA. Results were correlated with clinicopathological parameters and disease outcomes.ResultsExpression of caveolin-1 in stromal cells was observed in 14.4% of TNBC cases. TNBCs of the basal-like phenotype (85% of samples) were significantly more likely to exhibit stromal cell caveolin-1 expression (p=0.028), as were those with a trabecular growth pattern (p=0.007). Lack of stromal caveolin-1 expression in both TNBCs and those with the basal-like phenotype was significantly associated with worse overall survival (p=0.009 and p=0.026, respectively): accordingly, increasing mRNA levels of CAV1 in TNBC samples predicted better overall survival. Caveolin-1 expression on TNBC tumour cells was not associated with clinical outcome.ConclusionStromal, but not tumoural, caveolin-1 expression is significantly associated with survival in Asian women with TNBC.

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“…The presence of TRP63 is a proposed biomarker for basal cancer (Shekhar et al 2013, Thike et al 2010a) but not all investigations concur (Thike et al 2013, Buckley et al 2011). TRP63, KRT5 and smooth muscle actin (ACTA2) are expressed coordinately in normal basal mammary myoepithelial cells but are not invariably synchronously expressed in human breast cancers (Jumppanen et al 2007, Laakso et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Trp63 is regulated by STAT5 in mammary tissue and subject to differentiation in cancer

Assefnia¹,

Kang²,

Groeneveld³

et al. 2014

Endocrine-Related Cancer

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Trp63, founding member of the Trp53 family, contributes to epithelial differentiation and is expressed in breast neoplasia. Trp63 features two distinct promoters yielding specific mRNAs encoding two major TRP63 isoforms, a transactivating transcription factor and a dominant negative isoform. Specific TRP63 isoforms are linked to cell cycle arrest, apoptosis, survival and epithelial mesenchymal transition. Although TRP63 overexpression in cultured cells is used to elucidate functions, little is known about Trp63 regulation in normal and cancerous mammary tissue. This study used ChIP-seq to interrogate transcription factor binding and histone modifications of the Trp63 locus in mammary tissue and RNA-seq and immunohistochemistry to gauge gene expression. H3K4me2 and H3K4me3 marks coincided only with the proximal promoter, supporting RNA-seq data showing the predominance of the dominant negative isoform. STAT5 bound specifically to the Trp63 proximal promoter and Trp63 mRNA levels were elevated upon deleting STAT5 from mammary tissue, suggesting its role as a negative regulator. The dominant negative TRP63 isoform was localized to nuclei of basal mammary epithelial cells throughout reproductive cycles, and retained in a majority of the triple negative cancers generated from loss of full-length BRCA1. Increased expression of dominant negative isoforms was correlated with developmental windows of increased progesterone receptor binding to the proximal Trp63 promoter and decreased expression during lactation was correlated with STAT5 binding to the same region. TRP63 is present in the majority of triple negative cancers resulting from loss of BRCA1 but diminished in less differentiated cancer subtypes and in cancer cells undergoing epithelial mesenchymal transition.

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Ductal carcinoma in situ associated with triple negative invasive breast cancer: evidence for a precursor–product relationship

Cited by 23 publications

References 41 publications

Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients

Characteristics and behaviour of screen-detected ductal carcinoma in situ of the breast: comparison with symptomatic patients

Caveolin-1 expression as a prognostic marker in triple negative breast cancers of Asian women

Trp63 is regulated by STAT5 in mammary tissue and subject to differentiation in cancer

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