أهمية الخلايا التائية التنظيمية في سرطان الثدي وعلاقتها مع الواسمات الورمية عند النساء في محافظة كربلاء \ العراق

Importance of Regulatory T cells in Breast Cancer and its Association with Tumor Markers in Women of Kerbala Governorate , Iraq

abstract

Summary
Regulatory T cells ( T reg) are considered one of the most important types of cells in suppressing immunity, and their percentage is low in the blood. They are one of the types of T cells that mediate immune tolerance and prevent autoimmunity by inhibiting multiplying T cells and cytokines. Cancer cells contribute to the production of Treg cells, as they are found in several types of cancers because Cancer cells produce TGF-beta to stimulate myeloid cells, which plays an important role in the development of organisms by converting original T cells into T reg.
The aims of this study were to evaluate the role of T reg, CD28 and (cytotoxic T lymphocyte antigen 4 (CTLA-4), which were calculated by using the flow cytometry technique, in breast cancer, and to evaluate some of the existing tumor markers estrogen receptor (ER), progesterone receptor (PR), human epithelial receptor 2 \neu, B cell lymphocyte 2 and ki67 . In breast tissue using the immunehistochemical technique, 75 women were subjected to the current study. 25 women were normal, which was the control group. 25 women had malignant breast cancer, and the remaining 25 were women with benign breast cancer.
Samples (blood and biopsy ) were collected as an initial diagnosis of the type of breast cancer, whether benign or malignant was achieved. In Kerbala Governorate, female patients were classified according to age group into young patients, whose ages range from 29 to 49, and the second older category, which ranges from 50 to 70 years.
The results showed that there was a clear and significantly increased in Treg cells in (benign and malignant ) breast cancer compared to the control group, (45.61 and 43.42)% respectively . As for the molecules CD28 and their expression on the T reg cells, it was found that their expression decreased in (benign and malignant ) breast cancer compared with control (87.37 and 90.39)% respectively, and the significant differences. As for the mean fluorescence intensity (MFI), the group of patients showed an increased comparative with the control group, especially the benign breast cancer group (41.20)%. As for the expression of the CTLA4 molecule, there was a decrease in the percentage of these molecules compared to the control group, (56.14% in benign ) and (49.53% in malignant ). There was a significant and noticeable decrease, as the p ≤ 0.0001 compared to the control group.
The effect of age on the percentage of breast tissue expression of tumor markers for the malignant breast cancer group was studied. The results were showed that KI67 increased its expression in the breast tissue of the age group (29-49) years, with clear significant differences. The p ≤ 0.01, but for the rest of the markers ( ER, PR, HER2\neu and BCL2), no significant differences appeared. Clearly significant, its expression in breast tissue and the age of patients is evident.
As for the effect of age on Treg cells, the results showed that there was a clear increased in these cells in the two patient groups (benign and malignant), compared to the control group for both age groups. In addition, the control group with an age group of more than 50 years showed significant increased compared with the younger age group less than 50 years in the same group, with a significant difference, the p ≤ 0.01. While the group has the highest percentage of Treg cells, it was the benign cancer group, under 50 years of age, with a clear significant difference, p < 0.0001, while in the malignant breast cancer group, there was an increase in Treg cells with the same significant difference. The same can be said with the age group over 50 years compared to the control group.
The relationship of Treg cells with histological tumor markers of breast cancer was also studied. It was observed that there was non-significant an increase in the percentage of these cells in women with positive expression of these tumor markers. As for the tumor marker Ki 67, there was a positive relationship between it and Treg cells.
As for the patients’ blood group, its effect on the increased or decreased of T reg cells was studied. The results showed that the highest percentage of these cells appeared in the B blood group (51.98%) in the group of patients with benign breast cancer, followed by the blood group O(51.47%), then blood group A(43.32%), and finally blood group AB(29.32%). While the highest percentage of Treg cells was in blood group O(47.55%), then blood group A(45.02%), and the least in blood group B (32.46%) in the malignant breast cancer group.
As for the correlation of blood group with breast cancer, it was investigated, and the results showed that in benign breast cancer the highest percentage was blood type A(40%), blood group O (36%) it was the most closely related to blood group A. As for the malignant breast cancer group, the majority of women with breast cancer were of blood group A (44%), followed by blood group O (36%), and finally blood group B.
In the histological study, the results showed, The percentage of breast tumors expressing estrogen receptor reached 86%, and the percentage of progesterone in tumor tissues was 64%, while her2-neu had a positive expression rate of only 7%, while 93% of patients did not express this marker in their tissues. As for BCL2, the expression percentage was approximately 64% positive expression.
Ki 67, in the tissues of the patients was differed in the percentage of expression of this tumor marker. The percentages ranged from 12 to 80% and they were divided into two categories. The first category was the lower expresseion (35%) of this marker and the other category was the higher expression of 35%. The results showed that the percentage of women who had their breast tissue expressed the second category, which is more than 35%, and them reached 75%.
Also studied the percentage of the relationship between hormone receptors and breast cancer. The largest percentage was when the tumor was double positive for receptors for the hormones estrogen and progesterone, and the percentage of women was 57%, while the relationship of age with double receptors. Hormones: The highest percentage of women with double positive receptors for the hormones progesterone and estrogen were among women who were younger than 50 years, while the relationship of double receptors with the tumor marker Her2-neu was the percentage of positive expression of this marker in women with positive expression of estrogen and negative expression of progesterone. As for BCL2, it was the highest expression rate was in women whose tissues showed double positive expression of the hormones progesterone and estrogen.
Finally, the conclossion about this study , T regulatory cell might be stopped immune activity normal reactivity to cancers, which could explain why immune system-based therapies for breast and other malignancies do not work. Every essential medicine stop growth of T regulatory cell in carcinoma may work in conjunction with regular or boosted immunity to help fight tumors.