Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer

Dobrescu, Andrei; Chang, Monique; Kirtani, Vatsala; Turi, George K.; Hennawy, Randa; Hindenburg, Alexander

doi:10.5402/2011/673790

Cited by 9 publications

(5 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The current study showed that high FEN1 expression is significantly associated with aggressive behaviour of DCIS. Similar to previous studies [54][55][56], the current study showed high expression of FEN1 is associated with ER and PR negativity. Abdel-Fatah et al [36] reported that FEN1 could interact directly with ER and increase the interaction of ER-α with DNA-containing oestrogen response elements and impact the expression of oestrogen-responsive genes in cells.…”

Section: Discussionsupporting

confidence: 91%

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

Al-Kawaz

Miligy

Toss

et al. 2021

Breast Cancer Res Treat

View full text Add to dashboard Cite

Background Impaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS). Methods Expression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC); n = 239) using immunohistochemistry (IHC). Results FEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval. Conclusion High FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.

show abstract

Section: Discussionsupporting

confidence: 91%

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

Al-Kawaz

Miligy

Toss

et al. 2021

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…Breast cancer evolves from normal epithelial ducts through a sequence of increasingly abnormal proliferative lesions that begin with atypical hyperplasia, to pre-malignant in situ disease, before progressing into neoplasia [47,48]. DCIS is characterized by epithelial carcinoma within the ducts, surrounded by myoepithelial cells and with the basement membrane intact [49].…”

Section: Discussionmentioning

confidence: 99%

TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets

Wong

Hussain

2020

PLoS ONE

View full text Add to dashboard Cite

Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10 −11 ). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4 + ; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4 + ; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.

show abstract

“…It suggests that these tumors do not need as much of this protein once they become invasive. Higher expression levels of other proteins have also been reported in DCIS including ER, PR, and Her-2neu receptors [ 34 , 35 ], suggesting that some tumors express variable levels depending on which is the critical step(s) in tumorigenesis. Genomic instability tends to correlate with triple negative (ER/PR/Her-2neu-receptor negative) breast cancer [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer

Chen

Dahlstrom

Chandra

et al. 2012

Breast Cancer Res Treat

View full text Add to dashboard Cite

Long interspersed nuclear element 1 (L1) belongs to a family of retrotransposons. Expression of the normally repressed L1 retrotransposons has been shown to induce genome instability by creating DNA double-stranded breaks and chromosomal rearrangements through the process of retrotransposition. At present, little is known about the expression of L1-encoded ORF1p and ORF2p which are indispensable for its retrotransposition activity. Given its potentially harmful effects on the genome, we investigated the implications of both ORF1p and ORF2p expression and their subcellular localization in a range of breast cancer cell lines and breast tumor tissues including 15 normal breast tissues, 25 fibroadenomas, 25 ductal carcinomas in situ (DCIS), and 95 invasive cancers. Clinicopathologic parameters and survival outcomes were investigated in association with the cytoplasmic and nuclear expression of ORF1p and ORF2p using univariate and multivariate analysis. High cytoplasmic expression of ORF1p and ORF2p was seen in DCIS tumors, but they were not related with survival outcome. The majority of invasive cancers were found to express both ORF1p and ORF2p in the cytoplasm, while nuclear expression was also seen in a subclass of those invasive cancers in the range of 28–31 %. Tumors with high nuclear expression of ORF1p and ORF2p were more significantly associated with lymph node metastasis (p = 0.001) and the worst patient survival (p < 0.0001) than those with cytoplasmic expression. This is the first study examining the effects of both ORF1p and ORF2p expression in breast cancer tissues. Our observation shows altered expression patterns of ORF1p and ORF2p within invasive cancers, which are related to differences in overall patient survival. The differing patterns of both cytoplasmic and nuclear ORF1p and ORF2p expression indicate that further studies of the biology and function of L1 retrotransposons are required in breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-012-2246-7) contains supplementary material, which is available to authorized users.

show abstract

Study of Estrogen Receptor and Progesterone Receptor Expression in Breast Ductal Carcinoma In Situ by Immunohistochemical Staining in ER/PgR-Negative Invasive Breast Cancer

Cited by 9 publications

References 23 publications

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

The prognostic significance of Flap Endonuclease 1 (FEN1) in breast ductal carcinoma in situ

TRPM4 is overexpressed in breast cancer associated with estrogen response and epithelial-mesenchymal transition gene sets

Prognostic value of LINE-1 retrotransposon expression and its subcellular localization in breast cancer

Contact Info

Product

Resources

About