Fications [2] [3]. miRNAs, partially due to their size, are potentially more 57773-63-4 robust to FFPE-dependent degradation than mRNAs. Therefore miRNAs could be a viable alternative for expression profiling. Furthermore, it has been demonstrated in multiple studies that miRNAs are minimally affected by FFPE treatment, as isolated miRNAs displayed reliable expression levels as compared to frozen tissue samples [4] [5] [6] [7]. Although extensive research on molecular mechanisms involved in breast cancer has been done recently, challenges still prevail in the early diagnosis 11967625 and management of breast cancer patients, such as unpredictable response and development of resistance to adjuvant therapies. miRNAs, as regulators of protein-coding genes, could serve as novel diagnostic and prognostic candidates, and thus as potential therapeutic targets. Recent studies have indicated that circulating miRNAs may serve as minimally invasive biomarkers for cancer diagnosis [8]. Since the deregulation of miRNA in breast cancer was first reported in 2005 [9], there have been many studies on the expression of various miRNAs and their roles in breast cancer (Table 1). miRNA profiling studies have led to the identification of miRNAs that are aberrantly expressed in human breast cancer, with miR-10b, miR125b and miR-145 being down-regulated and miR-21 and 155 being up-regulated. Tumor formation may arise from miRNA deregulation. Iorio et al. [9] identified 29 miRNAs that were differentially expressed in breast cancer tissue compared to normal tissue, and a further set of 15 miRNAs that could be used to discriminate between tumor from normal cells. In addition, miRNA expression has been correlated with biopathological features such as ER and PR expression (miR-30) as well as tumor stages (miR-213 and miR-203). Differential expression of several let7 isoforms was associated with PR status (let-7c), lymph node MedChemExpress LED-209 metastasis (let-7f-1, let-7a-3, let-7a- 2), or high proliferation index (let-7c, let-7d) in tumor samples. Mattie et al. identified unique sets of miRNAs associated with breast cancers currently defined by their HER2 or ER/PR status [10]. miRNAs exert their function by directly targeting downstream genes and their associated pathways with sequence preference on mRNA seed sequence [11]. They can function as either tumor suppressors [12?5] or oncogenes (sometimes refer to as oncomir) [16?3]. Thus, tumor formation, progression and metastasis may arise from a suppression of tumor suppressor miRNAs and/or overexpression of an oncogenic miRNA. We attempt to profile miRNA expression patterns to identify potential biomarkers for the diagnosis of preinvasive breast lesions. In this study, we identified 8-patient FFPE blocks that contain multiple components of the tissue, such as histologically normal epithelial, ADH, DCIS and/or invasive tumor cells. We microdissected each sample as described earlier [24] and collected tissue samples. Total RNAs were isolated for miRNA microarray analysis. We observed different miRNA expression patterns between different subgroups, which may allow us to identify unique miRNA signatures for each neoplasm type. AfterTable 1. Microdissected samples from breast cancer FFPE blocks.PatientsLesions NORMAL ADH X B2 X D2 E2 X G2 X DCIS A3 B3 C3 D3 X F3 X X IDC A4 B4 C4 X E4 F4 G4 HA B C D E F G HA1* B1 C1 D1 E1 F1 G1 H*The letters (A, B, C …) represent each patient and the numbers, 1, 2, 3, 4 indicate “Normal”, “ADH”, “DCIS”, “IDC” respe.Fications [2] [3]. miRNAs, partially due to their size, are potentially more robust to FFPE-dependent degradation than mRNAs. Therefore miRNAs could be a viable alternative for expression profiling. Furthermore, it has been demonstrated in multiple studies that miRNAs are minimally affected by FFPE treatment, as isolated miRNAs displayed reliable expression levels as compared to frozen tissue samples [4] [5] [6] [7]. Although extensive research on molecular mechanisms involved in breast cancer has been done recently, challenges still prevail in the early diagnosis 11967625 and management of breast cancer patients, such as unpredictable response and development of resistance to adjuvant therapies. miRNAs, as regulators of protein-coding genes, could serve as novel diagnostic and prognostic candidates, and thus as potential therapeutic targets. Recent studies have indicated that circulating miRNAs may serve as minimally invasive biomarkers for cancer diagnosis [8]. Since the deregulation of miRNA in breast cancer was first reported in 2005 [9], there have been many studies on the expression of various miRNAs and their roles in breast cancer (Table 1). miRNA profiling studies have led to the identification of miRNAs that are aberrantly expressed in human breast cancer, with miR-10b, miR125b and miR-145 being down-regulated and miR-21 and 155 being up-regulated. Tumor formation may arise from miRNA deregulation. Iorio et al. [9] identified 29 miRNAs that were differentially expressed in breast cancer tissue compared to normal tissue, and a further set of 15 miRNAs that could be used to discriminate between tumor from normal cells. In addition, miRNA expression has been correlated with biopathological features such as ER and PR expression (miR-30) as well as tumor stages (miR-213 and miR-203). Differential expression of several let7 isoforms was associated with PR status (let-7c), lymph node metastasis (let-7f-1, let-7a-3, let-7a- 2), or high proliferation index (let-7c, let-7d) in tumor samples. Mattie et al. identified unique sets of miRNAs associated with breast cancers currently defined by their HER2 or ER/PR status [10]. miRNAs exert their function by directly targeting downstream genes and their associated pathways with sequence preference on mRNA seed sequence [11]. They can function as either tumor suppressors [12?5] or oncogenes (sometimes refer to as oncomir) [16?3]. Thus, tumor formation, progression and metastasis may arise from a suppression of tumor suppressor miRNAs and/or overexpression of an oncogenic miRNA. We attempt to profile miRNA expression patterns to identify potential biomarkers for the diagnosis of preinvasive breast lesions. In this study, we identified 8-patient FFPE blocks that contain multiple components of the tissue, such as histologically normal epithelial, ADH, DCIS and/or invasive tumor cells. We microdissected each sample as described earlier [24] and collected tissue samples. Total RNAs were isolated for miRNA microarray analysis. We observed different miRNA expression patterns between different subgroups, which may allow us to identify unique miRNA signatures for each neoplasm type. AfterTable 1. Microdissected samples from breast cancer FFPE blocks.PatientsLesions NORMAL ADH X B2 X D2 E2 X G2 X DCIS A3 B3 C3 D3 X F3 X X IDC A4 B4 C4 X E4 F4 G4 HA B C D E F G HA1* B1 C1 D1 E1 F1 G1 H*The letters (A, B, C …) represent each patient and the numbers, 1, 2, 3, 4 indicate “Normal”, “ADH”, “DCIS”, “IDC” respe.
