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Updated: May 29, 2026
Mutagenesis and Analysis of Genetic Mutations in the GC-rich KISS1 Receptor Sequence Identified in Humans with Reproductive Disorders
Published on: September 4, 2011
Clinical significance of KISS1 protein expression for brain invasion and metastasis
Ilya V Ulasov1, Natalya V Kaverina, Peter Pytel
1The Brain Tumor Cancer Center, The University of Chicago, Chicago, Illinois, USA.
Background:
Metastases to the brain represent a feared complication and contribute to the morbidity and mortality of breast cancer. Despite improvements in therapy, prognostic factors for development of metastases are lacking. KISS1 is a metastasis suppressor that demonstrates inhibition of metastases formation in several types of cancer. The purpose of this study was to determine the importance of KISS1 expression in breast cancer progression and the development of intracerebral lesions.
Methods:
In this study, we performed a comparative analysis of 47 brain metastases and 165 primary breast cancer specimens by using the antihuman KISS1 antibody. To compare KISS1 expression between different groups, we used a 3-tier score and the automated score computer software (ACIS) evaluation. To reveal association between mRNA and protein expression, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Significance of immunohistochemistry stainings was correlated with clinicopathological data.
Results:
We identified that KISS1 expression is significantly higher in primary breast cancer compared with brain metastases (P < .05). The mRNA analysis performed on 33 selected ductal carcinoma brain metastatic lesions and 36 primary ductal carcinomas revealed a statistically significant down-regulation of KISS1 protein in metastatic cases (P = .04). Finally, we observed a significant correlation between expression of KISS1 and metastasis-free survival (P = .04) along with progression of breast cancer and expression of KISS1 in primary breast cancer specimens (P = .044).
Conclusions:
In conclusion, our study shows that breast cancer expresses KISS1. Cytoplasmic expression of KISS1 may be used as a prognostic marker for increased risk of breast cancer progression.
Insights
KISS1 protein expression is lower in brain metastases than in primary breast cancer. Lower KISS1 levels correlate with increased breast cancer progression and risk, suggesting it as a prognostic marker.
Area of Science:
- Oncology
- Cancer Metastasis Research
- Molecular Pathology
Background:
- Brain metastases are a significant cause of mortality in breast cancer patients.
- Prognostic factors for brain metastasis development are currently limited.
- KISS1, a known metastasis suppressor, inhibits metastasis formation across various cancers.
Purpose of the Study:
- To investigate the role of KISS1 expression in breast cancer progression.
- To determine the association between KISS1 expression and the development of intracerebral lesions.
Main Methods:
- Comparative analysis of KISS1 expression in 47 brain metastases and 165 primary breast cancer specimens using immunohistochemistry.
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to correlate mRNA and protein expression.
- Correlation of KISS1 expression with clinicopathological data.
Main Results:
- KISS1 expression was significantly higher in primary breast cancer compared to brain metastases (P < .05).
- mRNA analysis revealed a significant down-regulation of KISS1 protein in metastatic cases (P = .04).
- Significant correlation observed between KISS1 expression and metastasis-free survival (P = .04) and breast cancer progression (P = .044).
Conclusions:
- Breast cancer expresses KISS1, with expression levels decreasing in metastatic lesions.
- Cytoplasmic KISS1 expression may serve as a prognostic marker for elevated risk of breast cancer progression.
