• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5483-5486
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• 2014

Recently, the transcription factor SOX11 has gained extensive attention as a diagnostic marker in a series of cancers. However, to date, the possible roles of SOX11 in breast cancer has not been investigated. In this study, immunohistochemical staining for SOX11 was performed for 116 cases of breast cancer. Nuclear SOX11 was observed in 42 (36.2%) and cytoplasmic SOX11 in 52 (44.8%) of breast cancer samples. Moreover, high expression of cytoplasmic and nuclear SOX11 was associated with clinicopathological factors, including earlier tumor grade, absence of lymph node metastasis and smaller tumor size. Kaplan-Meier survival curves demonstrated high nuclear SOX11 expression to be associated with more prolonged overall survival than those with low expression and it could be an independent predictor of survival for breast cancer patients. It is worthwhile to note that cytoplasmic SOX11 was not correlated with prognosis of breast cancer patients. These data suggest the possibility that nuclear SOX11 could be as a potential target for breast cancer therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1789-1795
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• 2016

Background: Breast cancer is the commonest female cancer worldwide and its propensity to metastasize negatively impacts on therapeutic outcome. Several clinicopathological parameters with prognostic/predictive significance have been associated with metastatic suppressor expression levels. The role of metastatic suppressor gene (MSG) KiSS1 in breast cancer remains unclear. Our goal was to investigate the possible clinical significance of KiSS1 breast cancer. Materials and Methods: The study was conducted on 87 histologically proven cases of breast cancer and background normal tiisue. Quantitative reverse transcriptase polymerase chain reaction (qRT PCR) and immunohistochemistry (IHC) were used to investigate KiSS1 at gene and protein levels, respectively, for correlation with several patient characteristics including age, family history, hormonal receptor status, stage, tumor size, nodal involvement and metastatic manifestation and finally with median overall survival (OS). Results: Our study revealed (i) KiSS1 levels were generally elevated in breast cancer vs normal tissue (P < 0.05). (ii) however, a statistically significant lower expression of KiSS1 was observed in metastatic vs non metastatic cases (P = 0.04). (iii) KiSS1 levels strongly correlated with T,N,M category, histological grade and advanced stage (p<0.001) but not other studied parameters. (iv) Lastly, a significant correlation between expression of KiSS1 and median OS was found (P = 0.04). Conclusions: Conclusively, less elevated KiSS1 expression is a negative prognostic factor for OS, advancing tumor stage, axillary lymph node status, metastatic propensity and advancing grade of the breast cancer patient. Patients with negative KiSS1 expression may require a more intensive therapeutic strategy.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1881-1886
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• 2012

Breast cancer is a heterogeneous disease that is affected by ethnicity of patients. According to hormone receptor status and gene expression profiling, breast cancers are classified into four molecular subtypes, each showing distinct clinical behavior. Lack of sufficient data on molecular subtypes of breast cancer in Iran, prompted us to investigate the prevalence and the clinicopathological features of each subtype among Iranian women. A total of 428 women diagnosed with breast cancer from 2002 to 2011 were included and categorized into four molecular subtypes using immunohistochemistry. Prevalence of each subtype and its association with patients' demographics and tumor characteristics, such as size, grade, lymph-node involvement and vascular invasion, were investigated using Chi-square, analysis of variance and multivariate logistic regression. Luminal A was the most common molecular subtype (63.8%) followed by Luminal B (8.4%), basal-like (15.9%) and HER-2 (11.9%). Basal-like and HER-2 subtypes were mostly of higher grades while luminal A tumors were more of grade 1 (P<0.001). Vascular invasion was more prevalent in HER-2 subtype, and HER-2 positive tumors were significantly associated with vascular invasion (P=0.013). Using muti-variate analysis, tumor size greater than 5 cm and vascular invasion were significant predictors of 3 or more nodal metastases. Breast cancer was most commonly diagnosed in women around 50 years of age and the majority of patients had lymph node metastasis at the time of diagnosis. This points to the necessity for devising an efficient screening program for breast cancer in Iran. Further, prospective surveys are suggested to evaluate prognosis of different subtypes in Iranian patients.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.503-511
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• 2018

Lysophosphatidic acid (LPA) is known to play a critical role in breast cancer metastasis to bone. In this study, we tried to investigate any role of LPA in the regulation of osteoclastogenic cytokines from breast cancer cells and the possibility of these secretory factors in affecting osteoclastogenesis. Effect of secreted cytokines on osteoclastogenesis was analyzed by treating conditioned media from LPA-stimulated breast cancer cells to differentiating osteoclasts. Result demonstrated that IL-8 and IL-11 expression were upregulated in LPA-treated MDA-MB-231 cells. IL-8 was induced in both MDA-MB-231 and MDA-MB-468, however, IL-11 was induced only in MDA-MB-231, suggesting differential LPARs participation in the expression of these cytokines. Expression of IL-8 but not IL-11 was suppressed by inhibitors of PI3K, NF-kB, ROCK and PKC pathways. In the case of PKC activation, it was observed that $PKC{\delta}$ and $PKC{\mu}$ might regulate LPA-induced expression of IL-11 and IL-8, respectively, by using specific PKC subtype inhibitors. Finally, conditioned Medium from LPA-stimulated breast cancer cells induced osteoclastogenesis. In conclusion, LPA induced the expression of osteolytic cytokines (IL-8 and IL-11) in breast cancer cells by involving different LPA receptors. Enhanced expression of IL-8 by LPA may be via ROCK, PKCu, PI3K, and NFkB signaling pathways, while enhanced expression of IL-11 might involve $PKC{\delta}$ signaling pathway. LPA has the ability to enhance breast cancer cells-mediated osteoclastogenesis by inducing the secretion of cytokines such as IL-8 and IL-11.

• Korean Journal of Head & Neck Oncology
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• v.18 no.1
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• pp.23-29
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• 2002

Mutation of the P53 tumor suppressor gene playa major role in the development of many carcinomas, namely in the colon, breast and bladder, whereas the role played by such mutations in thyroid carcinogenesis remains controversial. Vascular endothelial growth factor (VEGF) induces proliferation of endothelial cells, stimulates angiogenesis, and increases vascular permeability. Increased VEGF expression has been associated with poor clinical outcomes in many malignancies E-cadherin, a calcium-dependent transmembrane glycoprotein, is an adhesion molecule Expression of p53, VEGF and E-cadherin was assessed immunohistochemically in 19 tall columnar variant of papillary carcinoma, 24 common papillary carcinoma and 7 follicular carcinoma. The aim of this study was to evaluate the expression of P53,VEGF and E-cadherin as a potential maker for the prognosis of thyroid carcinomas. The results are as follows: 1) There were no significance in any clinical parameters examined among tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma. 2) The expression of P53 demonstrated low in tall columnar variant of papillary carcinoma, common papillary carcinoma and follicular carcinoma, but a significantly high in regional lymph node metastasis. 3) The expression of VEGF demonstrated a significantly high in regional lymph node metastasis than those without metastasis in papillary thyroid carcinoma. 4) The expression of E-cadherin demonstrated less often among papillary carcinomas with lymph node metastasis than in those without metastasis in papillary thyroid carcinoma. In conclusion, it is suggested that VEGF and E-cadherin will be useful for the diagnosis of thyroid carcinoma and serves as a biological marker for thyroid carcinoma lymph node metastasis.

• Nuclear Medicine and Molecular Imaging
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• v.42 no.6
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• pp.451-455
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• 2008

Purpose: Lymphoscintigraphy and sentinel node biopsy has become a standard method for detection of axillary lymph node metastasis in breast cancer patients, but the standard radiopharmaceutical was not prepared. About detection of axillary lymph node metastasis by lymphoscintigraphy and sentinel node biopsy in breast cancer patient, we compared the results of Tc-99m Tin-colloid and Tc-99m Phytate by subareolar injection. Materials and Methods: This study included 382 breast cancer patients who were performed operation during 2001-2008. Three hundred forty nine patients was injected 0.8ml of Tc-99m Tin-colloid (37-185 MBq) by subareolar injection. Thirty three patients was injected 0.8ml of Tc-99m Phytate (37-185 MBq). Lymphoscintigraphy was performed in supine position and sentinel node localization was performed by hand-held gamma probe in operation. Result: Among 349 patients by Tc-99m Tin-colloid, 312 cases (89.4%) localized the sentinel node by lymphoscintigraphy, 304 cases (87.1%) localized by gamma probe. Among 33 patients by Tc-99m Phytate, 32 cases (97.0%) localized by lymphoscintigraphy, 33 cases (100%) localized by gamma probe. Detection rate by lymphoscintigraphy and gamma probe was superior for Tc-99m Phytate compared to that with Tc-99m Tin-colloid, with a statistically significant difference. (p<0.05, p<0.05) Conclusion: Tc-99m Phytate is a better choice for localization of sentinel node than Tc-99m Tin-colloid in breast cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.6081-6084
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• 2013

Objective: Both estrogen receptors, ER alpha ($ER{\alpha}$) and ER beta ($ER{\beta}$), are expressed in 50-70% of breast cancer cases. The role of $ER{\alpha}$ as a prognostic marker in breast cancer has been well established as its expression is negative correlated with tumor size and lymph node metastasis. $ER{\beta}$ is also a favorable prognostic predictor although this is less well documented than for $ER{\alpha}$. Materials and Methods: To explore whether ERs independently or together might influence clinical outcome in breast cancer, the correlation between the ERs with the clinicopathological features was analyzed in 84 patients. Results: $ER{\alpha}$ expression negatively correlated with tumor stage (r=-0.246, p=0.028) and tended to be negatively correlated with lymph node status (r=-0.156, p=0.168) and tumor size (r=-0.246, p=0.099). Also, $ER{\beta}$ was negatively correlated with nodal status (r=-0.243, p=0.028), as was coexpression of $ER{\alpha}$ and $ER{\beta}$ (p=0.043, OR=0.194, 95% CI= 0.040-0.953). Conclusion: Coexpression of ERs might serve as an indicator of good prognosis in breast cancer patients.

• The Korean Journal of Cytopathology
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• v.6 no.1
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• pp.1-9
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• 1995

This study was carried out to determine the usefulness of imprint cytology for detecting p53 protein in breast carcinoma. NCL-DO7 (Novocastra, U.K.) was used to detect p53 protein immunocytochemically. A total of 33 cases was studied, Immunostaining of imprint cytology with NCL-DO7 was positive in 64% (21/33) and showed relatively high coincident rate (80%) with immunostaining of formalin-fixed, paraffin-embedded specimen p53 protein was related to negative estrogen receptor status, but not to the nuclear grade, lymph node metastasis, or tumor size. The fact that p53 protein expression was not related to nuclear grade might be due to predominance of nuclear grade 3. It was easier to determine the nuclear grade is one of the most important prognostic factors, in imprint cytology than in tissue specimen. p53 protein tended to be stained more strongly in imprint cytology than in tissue. It is concluded that the application of imprint cytology in p53 protein detection can be performed easily, and that it may contribute to the evaluation of prognostic factors in breast carcinoma.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3259-3264
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• 2012

Curcumin (CM) possesses anti-cancer activity against a variety of tumors. Matrix metalloproteinases (MMPs) play an important role in remodeling the extracellular matrix and their activities are regulated by tissue inhibitor of metalloproteinases (TIMPs) family. Control of MMP and TIMP activity are now of great significance. In this study, the effect of CM is investigated on metastatic MMPs and anti-metastatic TIMPs genes on MDA breast cancer cells cultured in a mixture of DMEM and Ham's F12 medium and treated with different concentrations of CM (10, 20 and $40{\mu}M$ for various lengths of time. Reverse transcription followed by quantitative real time PCR was used to detect the gene expression levels of MMPs and TIMPs in CM-treated versus untreated cases and the data were analyzed by one-way ANOVA. At high concentrations of curcumin, TIMP-1, -2, -3 and -4 genes were up-regulated after 48 hours of treatment, their over-expression being accompanied by down-regulation of MMP-2 and MMP-9 gene expression levels in a concentration- and time-dependent manner. These results suggest that curcumin plays a role in regulating cell metastasis by inhibiting MMP-2 and MMP-9 and up-regulating TIMP1 and TIMP4 gene expression in breast cancer cells.

• BMB Reports
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• v.49 no.10
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• pp.578-583
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• 2016

Special AT-rich sequence binding protein 1 (SATB1) is a nuclear matrix-associated DNA-binding protein that functions as a chromatin organizer. SATB1 is highly expressed in aggressive breast cancer cells and promotes growth and metastasis by reprograming gene expression. Through genome-wide cross-examination of gene expression and histone methylation, we identified SATB1 target genes for which expression is associated with altered epigenetic marks. Among the identified genes, long noncoding RNA urothelial carcinoma-associated 1 (UCA1) was upregulated by SATB1 depletion. Upregulation of UCA1 coincided with increased H3K4 trimethylation (H3K4me3) levels and decreased H3K27 trimethylation (H3K27me3) levels. Our study showed that SATB1 binds to the upstream region of UCA1 in vivo, and that its promoter activity increases with SATB1 depletion. Furthermore, simultaneous depletion of SATB1 and UCA1 potentiated suppression of tumor growth and cell survival. Thus, SATB1 repressed the expression of oncogenic UCA1, suppressing growth and survival of breast cancer cells.