Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor.
Metastatic breast cancer remains a highly lethal disease, and it is very important to evaluate the biomarkers associated with the distant metastasis. MicroRNA (miRNA) are small non-protein coding RNA that regulate various cellular functions. Recent investigations have demonstrated the importance of some miRNA in breast cancer, but the significance of the great majority of miRNA remains largely unclear in breast cancer metastasis. Therefore, in this study, we first examined expression profiles of miRNA in stage IV breast carcinoma tissues, comparing stage I-III cases by miRNA PCR array, and identified miR-1 as the miRNA which was the most associated with the distant metastasis. However, miR-1 has not yet been examined in breast carcinoma tissue, and its significance remains unknown. Therefore, we further examined miR-1 expression in breast carcinoma using in situ hybridization (ISH). miR-1 was localized in carcinoma cells in 20% of breast carcinoma cases, but it was negligible in non-neoplastic mammary glands or stroma. miR-1 ISH status was significantly associated with stage, pathological T factor, lymph node metastasis, distant metastasis, histological grade, estrogen receptor, progesterone receptor and Ki-67 in breast carcinoma. Moreover, the miR-1 status was demonstrated using multivariate analysis as an independent worse prognostic factor for both disease-free and breast cancer-specific survival. These findings suggest that abnormal miR-1 expression is associated with an aggressive phenotype of breast carcinoma and that miR-1 status is a potent prognostic factor in human breast cancer patients.
Department of Pathology and Histotechnology, Sendai, Japan.
Hiroyuki
H
Minemura
Department of Pathology and Histotechnology, Sendai, Japan.
Kiyoshi
K
Takagi
Department of Anatomic Pathology, Sendai, Japan.
Yasuhiro
Y
Miki
Department of Anatomic Pathology, Sendai, Japan.
Yukiko
Y
Shibahara
Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Saki
S
Nakagawa
Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Akiko
A
Ebata
Department of Pathology, Tohoku University Hospital, Sendai, Japan.
Mika
M
Watanabe
Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Takanori
T
Ishida
Department of Anatomic Pathology, Sendai, Japan.|Department of Pathology, Tohoku University Hospital, Sendai, Japan.
Hironobu
H
Sasano
Department of Pathology and Histotechnology, Sendai, Japan.
Takashi
T
Suzuki
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000096:biosynthesis*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D059467:Transcriptome
D014408:Biomarkers, Tumor; C544547:MIRN1 microRNA, human; D035683:MicroRNAs
Breast cancer; PCR array; in situ hybridization; microRNA; prognosis