Expression And Clinical Signiifcance Of Gli1in Invasive Breast Cancer

[Background]Breast cancer patients could be benefited from further research of tumor molecular mechanism and corresponding individual comprehensive therapy, Survival time of them is gradually prolonged. But there are still some patients with poor prognosis, just like Triple Negative Breast Cancer (TNBC). TNBC is one of molecular subtypes of breast cancer. Molecular typing method about breast cancer is much advanced to reflect the biological characteristics of different individual tumor than pathological typing methods. Molecular typing method which takes therapeutic methods and prognosis statuses between different subtypes into full consideration is good for guide clinical diagnosis and treatment. Hedgehog-gli signal transduction pathway is involved in the development of many tumors, just like breast carcinoma. Glioma-associated Oncogene Homolog1(Glil) is one of the important downstream transcription factors of pathway. It could reflect pathway state and directly activate the transcription of the target oncogenes. Kwon reported that Gli1could up-regulate Matrix Metalloproteinase (MMP) and promote growth of ER-negative breast cancer cell strains. Researched the Gli1expression in different molecular subtypes, could further understand the mechanism that the Hedgehog-gli pathway promotes growth of breast cancer and may find therapeutic targets from key elements of Hedgehog-gli pathway.【Objective】Examined the expression of Gli1in invasive breast cancer tissues and adjacent tissues, and analyzed the relationship between Gli1expression and breast cancer clinical characteristics. The differences of Gli1expression between different Ki-67related molecular subtypes were discussed. Matrix Metalloproteinases-9(MMP-9) and CD34expression were further examined in ER-negative breast cancer tissues. We discussed the relationship between Gli1and MMP-9, analyzed the capability that Gli1, MMP-9promoted ER-negative breast cancer vascular proliferation and tumor growth, metastasis. Finally, we discussed the clinical significance of Gli1expression for breast cancer diagnosis and therapy.【Methods】Selected166Invasive Breast Cancer tissues which from Department of Thyroid and Breast Surgery of Chang-hai Hospital and Pathology Department of Chang-hai Hospital since2010-1to2011-10, and selected15corresponding adjacent tissues for control study. All the tissues had definite pathological diagnosed breast cancer. All the patients are women. No one accepted any therapy for breast carcinoma. Minimum Age of patients was30, Maximum Age was86, and Median Age was54. TNM stages, I stages tissues were collected46cases, II stages were collected76cases, III to IV stages44cases. Tumor size, Ti size were collected57cases, T276cases, T3to T433cases. No were collected71cases, N1-395cases. Pathological Category, Infiltrating Ductal Carcinoma were collected104cases, Infiltrating Lobular Carcinoma38cases, Intraductal Carcinoma with part of the infiltration were collected20cases, Myxoadenocarcinoma patients3cases, Mammary Paget’s disease1cases. Immune index, ER-positive tissues were collected102cases, PR-positive89cases, P53high-expression73cases, HER-2positive expression41cases, Ki-67high-expression94cases. We examined Gli1expression in Invasive Breast Cancer tissues by Envision immunohistochemistry, and examined Gli1expression in adjacent tissues by the same way. Analyzed the relationship between Gli1expression and age, tumor size, TNM stages, lymph node metastasis, Pathological Category, ER, PR, P53, Ki-67, HER-2expression in Invasive Breast Cancer tissues. We discussed the differences of Gli1expression between different Ki-67related molecular subtypes, examined MMP-9, CD34expression in ER-negative Breast Cancer tissues by Envision immunohistochemistry. Analyzed the relationship between Gli1, MMP-9expression and MVD, tumor size, TNM stages, lymph node metastasis, HER-2in ER-negative Breast Cancer tissues. Enumeration data was processed by Chi-Square Test. Ranked data was processed by Mann-Whitney U Test or Kruskal-Wallis H Test. MVD data was processed by Oneway ANOVA. We used spearman analysis for correlation between Gli1and MMP-9expression.【Results】1. Gli1expression in Invasive Breast Cancer tissues were higher than Corresponding adjacent tissues (P<0.01). Gli1expression was related to tumor size, TNM stages, ER and Ki-67expression (P<0.05). Gli1expression was not related to age, lymph node metastasis, Pathological Category, PR, P53, HER-2expression (P>0.05).2. Gli1expression between ki-67related molecular subtypes had Total Difference (P<0.01). Positive rate of Gli1expression in Luminal A subtype, Luminal B subtype, HER-2enriched subtype, Basal-Like subtype were51.35%,81.25%,88.24%,96.15%. Among them, Gli1positive rate in Luminal A subtype that was compared with other subtypes was lowest, there were significant differences (P<0.01). Gli1positive rate in Basal-Like subtype was highest. But it was compared with HER-2enriched subtype, there was no significant differences (P>0.05). 3. The expression of CD34was enhanced by the expression of Gli1and MMP-9in ER-negative breast cancer tissues, There were significant differences (P<0.01). The expression of Gli1and MMP-9were correlated with tumor size and clinical TNM stages in ER-negative breast cancer (P<0.05). The expression of MMP-9was also correlated with lymphatic metastasis (P<0.05). The correlation was existed between the expression of Gli1and MMP-9in ER-negative group(r=0.462, P<0.01).【Conclusion】1. Gli1expression is lower or negative in normal breast tissues. It is positive in breast cancer tissues. Gli1positive expression is important for aided diagnose breast cancer.2. Gli1expression promotes tumor growth and stages progress in Invasive Breast Cancer. It is related to ER and Ki-67expression. Examined Gli1expression is helpful to aided judgment malignancy degree about Invasive Breast Cancer.3. Examined Gli1expression is helpful to diagnose Luminal A subtype. Gli1positive rate in Basal-Like subtype is highest. Maybe Gli1is the target for therapy TNBC.4. Gli1and MMP-9expression are able to promote microvascular proliferation, tumor growth, clinical stages progress in ER-negative breast cancer. Examined Gli1and MMP-9proteins in ER-negative breast cancer maybe contribute to the judgment of malignancy degree. There are other clinical influencing factors in the process that Gli1regulate the expression of MMP-9proteins. These influencing factors should be taken into account for analyzing the effect that The Hedgehog-Gli pathway promotes ER-negative breast cancer.