J Breast Cancer.  2012 Jun;15(2):162-171. 10.4048/jbc.2012.15.2.162.

Overexpression of Cell Cycle Progression Inhibitor Geminin is Associated with Tumor Stem-Like Phenotype of Triple-Negative Breast Cancer

• Di Bonito
• Cantile M
• Collina F
• Scognamiglio G
• Cerrone M
• La Mantia
• Barbato A
• Liguori G
• Botti G

• KMID: 2242186
• DOI: http://doi.org/10.4048/jbc.2012.15.2.162

Abstract

PURPOSE
Triple-negative breast cancer, has a significant clinical relevance being associated with a shorter median time to relapse and death and does not respond to endocrine therapy or other available targeted agents. For this reason, identifying the molecular pathways associated with increased aggressiveness, for example the presence of stem cell populations within the tumor and alteration of genes associated with cell cycle regulation represents an important objective in the clinical research into this neoplasm.
METHODS
To investigate the role of cell cycle progression inhibitor Geminin in triple-negative breast cancers and its potential correlation with stem-like phenotype of this neoplasm, we used tissue microarray technology to build a specific triple-negative breast cancer tissue micro-array. Geminin and cancer stem cell marker CD133 expression was further investigated at the mRNA level for selected breast tumor samples through realtime polymerase chain reaction quantification.
RESULTS
Our results showed that CD133 expression was significantly associated to high Geminin expression (p=0.017), a strong association between Ki-67 and tumor grade (p=0.020) and an inverse association between Geminin expression and lymphonode metastases (p=0.058), and a trend of statistically significance between Geminin marker expression and survival of triple-negative breast cancer patients (p=0.076).
CONCLUSION
The strong association between the expression of CD133 and Geminin could be useful in molecular stratification of breast tumors and in particular of triple-negative breast cancers.

Keyword

CD133 antigen; GMNN protein; Triple-negative breast cancer

MeSH Terms

Antigens, CD
Breast
Breast Neoplasms
Cell Cycle
Glycoproteins
Humans
Neoplasm Metastasis
Neoplastic Stem Cells
Peptides
Phenotype
Polymerase Chain Reaction
Recurrence
RNA, Messenger
Stem Cells
Antigens, CD
Glycoproteins
Peptides
RNA, Messenger

Figure

• 

  Figure 1 CD133 immunostaining. (A) Immunonegativity for CD133 in normal breast cells (×60). (B) Immunonegativity for CD133 in HER2+ breast sample (×60). (C) CD133 low cytoplasmatic expression in triple-negative (TN) sample 27 (×60). (D) CD133 moderate cytoplasmatic expression in TN sample 131 (×60). (E) CD133 high cytoplasmatic expression in TN sample 7 (×60). (F) CD133 high membranous expression in TN sample 127 (×60).

• 

  Figure 2 Geminin immunostaining. (A) Geminin low cytoplasmatic expression in normal breast cells (×60). (B) Immunonegativity for Geminin in HER2+ breast sample (×60). (C) Geminin low cytoplasmatic expression in triple-negative (TN) sample 27 (×60). (D) Geminin moderate cytoplasmatic expression in TN sample 131 (×60). (E) Geminin high cytoplasmatic expression in TN sample 7 (×60). (F) Geminin high cytoplasmatic expression in TN sample 127 (×60).

• 

  Figure 3 Geminin real time expression in breast samples. All reactions were performed in triplicate and data are expressed as the mean in the relative amount of mRNAs levels. TN=triple-negative.

• 

  Figure 4 Prominin-1/CD133 real time expression in breast samples. All reactions were performed in triplicate and data are expressed as mean of relative amount of mRNAs levels. TN=triple-negative.

• 

  Figure 5 Geminin overall survival Kaplan-Meier curves.

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