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Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.

Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C - Br. J. Cancer (2009)

Bottom Line: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation.Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032).These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Université Lyon 1, ISPB, Lyon F-69003, France.

ABSTRACT

Background: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer.

Methods: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR.

Results: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours.

Conclusion: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

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Related in: MedlinePlus

Immunohistochemical analysis of Dicer protein expression in normal and breast cancer tissues. (A) Low-intensity staining in the cytoplasm of epithelial luminal normal breast cells. Non-specific staining of mast cells. (B) Low-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. (C) High-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. Images are shown at magnification, × 40 (panels A–C).
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fig4: Immunohistochemical analysis of Dicer protein expression in normal and breast cancer tissues. (A) Low-intensity staining in the cytoplasm of epithelial luminal normal breast cells. Non-specific staining of mast cells. (B) Low-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. (C) High-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. Images are shown at magnification, × 40 (panels A–C).

Mentions: In a preliminary IHC analysis with eight normal mammary gland tissues, Dicer protein was found to be expressed uniformly in the cytoplasm of the luminal cells (Figure 4A). The signal within the cytoplasm of luminal cells was weak (corresponding to intensity 1). No positive immunoreactivity was found either in basal or in stromal cells. In mammary tumour cells, Dicer showed variable expression patterns. Some tumours were negative for Dicer staining (data not shown), whereas other tumour tissues showed a staining intensity comparable with that found in normal tissues (intensity 1 and >60% of stained cells) (Figure 4B). Nevertheless, other tumours showed stronger cytoplasmic Dicer staining with a non-uniform pattern in a reduced tumour cell population (intensity 2 and ⩽60% of stained cells) (Figure 4C). We have found a significant inverse correlation between staining intensity and percentage of stained cells (P=0.013, Supplementary Table S3); therefore, either can be used as a staining score. The majority (67%) of tumours in TMA analysis (58 out of 86) was of staining intensity 1 and 62% (36 out of 58) of them showed more than 60% of stained cells compared with only 29% (5 out of 21) of tumours showing staining intensity scored as 2 (Supplementary Table S3).


Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype.

Grelier G, Voirin N, Ay AS, Cox DG, Chabaud S, Treilleux I, Léon-Goddard S, Rimokh R, Mikaelian I, Venoux C, Puisieux A, Lasset C, Moyret-Lalle C - Br. J. Cancer (2009)

Immunohistochemical analysis of Dicer protein expression in normal and breast cancer tissues. (A) Low-intensity staining in the cytoplasm of epithelial luminal normal breast cells. Non-specific staining of mast cells. (B) Low-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. (C) High-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. Images are shown at magnification, × 40 (panels A–C).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2736830&req=5

fig4: Immunohistochemical analysis of Dicer protein expression in normal and breast cancer tissues. (A) Low-intensity staining in the cytoplasm of epithelial luminal normal breast cells. Non-specific staining of mast cells. (B) Low-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. (C) High-intensity staining in the cytoplasm of infiltrating ductal carcinomatous cells. Images are shown at magnification, × 40 (panels A–C).
Mentions: In a preliminary IHC analysis with eight normal mammary gland tissues, Dicer protein was found to be expressed uniformly in the cytoplasm of the luminal cells (Figure 4A). The signal within the cytoplasm of luminal cells was weak (corresponding to intensity 1). No positive immunoreactivity was found either in basal or in stromal cells. In mammary tumour cells, Dicer showed variable expression patterns. Some tumours were negative for Dicer staining (data not shown), whereas other tumour tissues showed a staining intensity comparable with that found in normal tissues (intensity 1 and >60% of stained cells) (Figure 4B). Nevertheless, other tumours showed stronger cytoplasmic Dicer staining with a non-uniform pattern in a reduced tumour cell population (intensity 2 and ⩽60% of stained cells) (Figure 4C). We have found a significant inverse correlation between staining intensity and percentage of stained cells (P=0.013, Supplementary Table S3); therefore, either can be used as a staining score. The majority (67%) of tumours in TMA analysis (58 out of 86) was of staining intensity 1 and 62% (36 out of 58) of them showed more than 60% of stained cells compared with only 29% (5 out of 21) of tumours showing staining intensity scored as 2 (Supplementary Table S3).

Bottom Line: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation.Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032).These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Université Lyon 1, ISPB, Lyon F-69003, France.

ABSTRACT

Background: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer.

Methods: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription-PCR.

Results: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P=0.008; PR P=0.019; cancer subtype P=0.023, luminal A P=0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio=3.36, P=0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours.

Conclusion: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

Show MeSH
Related in: MedlinePlus