Immunohistochemical and genetic study in Iraqi women with breast cancer

العناوين الأخرى

دراسة مناعية-نسيجية و وراثية للنساء العراقيات المصابات بسرطان الثدي

مقدم أطروحة جامعية

Abd al-Jabbar, Rawa Abd al-Amir

مشرف أطروحة جامعية

Adhiah, Ali Husayn
al-Rikabi, Abd al-Amir Nasir Ghalub

الجامعة

جامعة بغداد

الكلية

كلية العلوم

القسم الأكاديمي

قسم علوم الحياة

دولة الجامعة

العراق

الدرجة العلمية

دكتوراه

تاريخ الدرجة العلمية

2014

الملخص الإنجليزي

The study aimed to shed light on some profiles (histopathological classification, demographic presentation, ABO blood group polymorphism, cytogenetic analysis of cultured blood lymphocytes, serum level of estradiol, immunohistochemical evaluation of estrogen, progesterone, HER-1 and HER-2 receptors, tumor-infiltrating immune cells defined by CD4, CD8 and CD68 markers, tumor expression of T-bet, GATA3, IL-17A and FOXP3, and mutational change in exon 3 and exon 7 of estrogen-β gene) of breast tumor (benign and malignant) in a sample of Iraqi female patients; each with 30 participants, who were referred to the Center for Early Detection of Breast Tumor at Al-Alwayia Hospital for Gynecology and Obstetrics (Baghdad) during the period June-December 2011.

Three control groups were also enrolled: married and had children (Married Group), married but had primary infertility (Infertile Group) and single women (Single Group); each with 10 subjects.

The following results were reached: 1.

A histopathological examination of benign breast tumor (BT) biopsies revealed that 56.7% were presented as fibroadenoma.

Two less frequent types were also observed: fibrocystic changes (26.7%) and mammary duct ectasia (16.7%).

For malignant BT, two histopathological types were encountered: invasive ductal carcinoma (IDC) and ductal carcinoma in situ (DCIS) with frequencies of 86.7 and 13.3%, respectively.

Clinical staging of malignant BTs based on TNM grouping revealed that stage II was the most frequent (50.0%), followed by stages III (26.7%) and I (23.3%).

2.

Demographic presentation of malignant and benign BT cases included age at presentation (50.2 ± 1.8 vs.

39.0 ± 2.1 years), menarche age, marriage age, menopausal status, lactation period, oral contraceptive use, family history of breast cancer or other cancers and body mass index.

For malignant BT, 50.0% of patients reached menopause in comparison with 20.0% in benign cases, and the difference was significant (P = 0.015).

It was also observed Summary =================================================================== ii that 60.0% of malignant patients used oral contraceptives, while it was lower in benign patients or married women (20.0% in each group), and such differences attended a significant level at P ≤ 0.01.

Positive family history of breast cancer accounted for 43.3% in malignant cases, while it was less frequent (20.0%) in benign cases, and the difference was significant (P = 0.047).

With respect to body mass index, overweight (25-29.9 Kg/m2) and obese (30-40 Kg/m2) cases accounted for 43.3 and 26.7%, respectively in malignant patients, while they were 36.7 and 33.3%, respectively in benign patients.

Furthermore, most of married and infertile women were overweight (80.0%), while in single women, it accounted for only 20.0%.

Such differences were significant at P ≤ 0.01.

3.

The distribution of ABO blood group phenotypes demonstrated a significant difference (P ≤ 0.05) between malignant patients and controls, but not between benign patients and controls.

Such significant difference was mainly contributed by an increased frequency of B phenotype (36.7 vs.

16.7%) and a decreased frequency of O phenotype (26.7 vs.

55.0%) in malignant patients.

4.

Serum level of estradiol was significantly increased in malignant BT patients (1134.7 ± 159.3 pg/ml) as compared with benign BT patients (72.6 ± 10.3 pg/ml) or married (16.8 ± 3.4 pg/ml), single (32.7 ± 9.4 pg/ml) and infertile (22.5 ± 3.6 pg/ml) women.

5.

Cytogenetic analysis of blood lymphocytes revealed that the highest blast index was observed in malignant patients (14.99 ± 1.04%), followed by benign patients (10.29 ± 0.23%), and the difference was significant (P ≤ 0.05), but both means were significantly (P ≤ 0.05) higher than the means in married (6.32 ± 0.49%), single (6.56 ± 0.52%) and infertile (6.90 ± 0.63%) women.

The metaphase index behaved in a similar manner and malignant patients scored the highest mean (12.61 ± 0.71%), followed by benign patients (6.48 ± 0.28%), and finally married (0.24 ± 0.07%), single (0.43 ± 0.11%) and infertile (0.26 ± 0.09%) women.

Summary =================================================================== iii 6.

Estrogen-α receptor (ER-α) was positive in 20.0% of malignant BTs, while only 6.7% of benign BTs were positive for this receptor.

In contrast progesterone receptor (PgR) was less frequent in malignant BTs than in benign BTs (26.7 vs.

43.3%).

With respect to HER-1, 20.0% of malignant BTs were positive for this receptor in comparison with 30.0% in benign BTs, and the opposite picture was observed in HER-2 (26.7 vs.

20.0%).

In addition, 60.0% of malignant BTs were triple-negative for ER, PgR and HER-2, while in benign BTs, a lower frequency was observed (46.7%).

However, these differences were not significant.

7.

All malignant BTs (100.0%) were positive for CD4 and CD8 (T-helper and - cytotoxic markers, respectively), while the corresponding frequencies in benign BTs were 79.3 and 75.9%, respectively, and the difference was significant.

For CD68 (macrophage marker), both BTs were 100.0% positive.

8.

Malignant BTs showed a significantly higher frequency of positive cases for T-bet (T helper-1 factor) in comparison with benign BTs (93.3 vs.

72.4%), while, GATA3 (T helper-2 factor) showed no significant difference between malignant and benign BTs (66.7 vs.

62.1%).

The expression of IL-17A (T helper-17 marker) was more frequently in malignant BTs than benign BTs (96.7 vs.

69.0%), and the difference was significant (P = 0.005).

FOXP3 (T regulatory marker) was expressed in 83.3% of malignant BTs, while it was observed in 27.6% of benign BTs, and such difference was highly significant (P = 1.7 x 10-5).

9.

Conventional PCR analysis of ER-β gene for specific sequences in exons 3 and 7 revealed that 20.0% malignant BT patients did not show the band of exon 3 (PCR amplified product) after agarose-gel electrophoresis, while the rest of patients and controls showed the band.

For exon 7, 80.0% of malignant BT patients and 23.3% benign BT patients did not show the band, while all women of controls (100%) showed the band.

These differences were highly significant with a probability range of 0.01 - 1.7 x 10-11.

التخصصات الرئيسية

الطب البشري

الموضوعات

• السرطان(مرض)
• العراق
• الثدي
• الجوانب الوراثية

عدد الصفحات

143

قائمة المحتويات

• APA
• MLA
• AMA

لغة النص

الإنجليزية

نوع البيانات

رسائل جامعية

رقم السجل

BIM-599107