الفهرس 
TitleOnly 14 pages are availabe for public view
Abstract
Breast cancer is the second most common cancer in the world and the most frequent
among women. Breast cancer can be classified according to the three
immunohistochemistry (IHC) markers into four main molecular subtypes which include
luminal-A, luminal-B, HER2 enriched, and basal cell-like (BCL) or triple-negative breast
cancer (TNBC). Metastasis suppressors are attractive agents to treat metastasis. Several
metastasis suppressor genes were identified, including the KISS1 gene, which encodes for a
145 amino acid protein known as kisspeptin-145, that undergoes a series of proteolytic
cleavage resulting in kisspeptin-14, -13 and -10. All of these kisspeptin fragments can
activate the KISS1 receptor (KISS1R). The KISS1R is a 398 amino acid peptide and a
member of the rhodopsin family of G-protein coupled receptors. Its metastasis related role
in breast cancer remains controversial
The present study aimed to measure mRNA gene expression of KISS1 receptor in
healthy and cancerous breast tissue of patients with breast cancer, and to evaluate the
association of its level with the available molecular subtypes and the traditional clinicopathological
variables.
The study was conducted on 41 operable primary breast cancer patients, from whom
biopsy from both tumor tissue and surrounding normal healthy mammary tissue was taken
following radical surgery done with a safety margin. All cases were subjected to a full
clinical examination to exclude other types of malignancies as well as radiological
investigations. The histopathologically confirmed diagnosis of breast cancer (including
staging) was subjected to immunohistochemical studies to determine the status of estrogen
receptor, progesterone receptor and human epidermal growth factor-2 receptor (HER2).
Relative quantification of KISS1R mRNA expression level was done using a quantitative
real time PCR (qRT-PCR).
In the present study, KISS1R mRNA expression was significantly higher in cases
presenting with stage III compared to cases presenting with stage II cancer. At a cut-off
value for KISS1R mRNA expression of 1.75, stage II was discriminated from stage III with
a diagnostic sensitivity of 77.78 % and a specificity of 95.65 %, with an overall test
accuracy of 87.80%. Furthermore, significant positive correlations were found between
KISS1R mRNA expression and each of tumor size and lymph nodes metastasis.
As regards its relation to immunohistochemical markers, KISS1R mRNA was highly
expressed in ER negative cases compared to ER positive ones, and again was highly
expressed in PR negative cases compared to PR positive ones.
The current study found that there was a statistically significant difference in KISS1R
mRNA expression levels and different molecular subtypes being over-expressed in HER2
and triple negative cancer cases.
In conclusion, our results support studies suggesting that KISS1R may not be
functioning as a metastasis suppressor in breast cancer, being over-expressed in advanced
stages of breast cancer and hence it can be used as a prognostic marker for aggressiveness
of breast cancer. Moreover, its over-expression in triple negative patients could represent a
promising therapeutic target in triple negative cases.
Summary, Conclusion and Recommendations
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Recommendations
In order to continue future research in that field we recommend the following:
1. Conducting such a study on a larger sample size of Egyptian female breast cancer
patients.
2. Proteomic analysis of the kisspeptin protein fragments in relation to the KISS1R
mRNA expression in breast cancer cases.
3. Follow up of the patients to detect the role of KISS1R mRNA expression in
determination of recurrence and its association with survival of patients.
4. Further studies are needed to determine the expression level of KISS1R in metastatic
versus non-metastatic breast cancers.
5. Determination of KISS1R mRNA expression in a larger number of TNBC Egyptian
patients and its association with the expression level of some drug resistance genes such
as breast cancer resistance protein to investigate its possible use in targeted therapy.