الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Although considerable treatment advances have been made since the early 2000s, metastatic disease continues to be a major cause of death in breast cancer patients. It is well documented that defects in cell adhesion are common in the majority of metastatic human cancers. In the metastatic process, tumor cells acquire the ability to change their shape, detach and easily move through spaces disorganizing the normal tissue architecture. This property is due to changes in expression levels of adhesion molecules and/or due to altered levels of secreted proteolytic enzymes, including MMPs.
Matrix metalloproteinases (MMPs) are implicated in the development of cancers including breast cancer. In this respect, animal and cell line studies indicate a paradoxical inhibitory effect of MMP8 on tumorigenesis and metastasis.
E-cadherin is a cell adhesion molecule critical for appropriate embryonic and mammary gland development. In cancer, the disruption of E-cadherin expression and/or signaling leads to the loss of cell contact integrity and initiation of the metastatic cascade.
So, the present study was conducted to investigate the role of MMP-8 and E-cadherin in breast cancer patients and their relation to metastasis.
The study was conducted on a total of 80 females who were divided into four groups; 10 normal healthy females, 10 patients with benign breast lesions, 30 patients with non metastatic breast cancer and 30 patients with metastatic breast cancer.
The mean age of studied groups were 44.0±6.46, 37.40± 7.21, 52.03 ±10.39 and 48.43±11.62 years in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer, respectively.
All subjects under study were subjected to thorough history taking and clinical examination as well as routine laboratory investigations including liver function tests (SGOT, SGPT), kidney function tests (urea, creatinine) and complete blood picture.
The mean SGOT levels in normal females, patients with benign breast lesions, patients with non-metastatic BC and patients with metastatic breast cancer, were 9.10 ± 1.66, 8.80 ± 2.74, 42.03 ± 109.81and 33.03 ± 32.04 IU/L, respectively. The mean serum SGOT levels were significantly increased (p< 0.001) in both groups of breast cancer patient as compared with normal females as well as patients with benign breast lesions.
The mean SGPT levels in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer, were 5.10 ± 1.0, 7.60 ± 2.67, 24.63 ± 25.34 and 30.63 ± 26.72 IU/L, respectively. When compared with normal females, the mean serum SGPT was significantly increased in patients with benign breast lesions (P=0.028) as well as breast cancer patients (p< 0.001). The corresponding levels were significantly increased in both breast cancer patient groups when compared with patients having benign breast lesion (p< 0.001).
The mean urea levels in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer, were 32.40 ± 7.50, 41.40 ± 7.65, 29.60 ± 17.39 and 30.47 ± 9.94 mg/dl, respectively. The mean level of serum urea was significantly increased in patients with benign breast lesions than that in normal females (p= 0.034). The mean serum urea levels were significantly lower in non metastatic (p = 0.001) and metastatic (p = 0.002) breast cancer groups than that in patients having benign breast lesions.
The mean creatinine levels in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer, were 0.76 ± 0.18, 0.97 ± 0.19, 1.21 ± 0.96 and 0.92 ± 0.17 mg/dl, respectively. When compared with normal females, the mean serum creatinine levels were significantly increased in patients with benign breast lesions, non metastatic - and metastatic breast cancer (p= 0.029, 0.001 and 0.022, respectively). The corresponding level was significantly increased in patients with non metastatic breast cancer than in cases with metastatic breast cancer (P=0.025).
The mean Hb levels in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer were 12.19 ± 0.61, 11.76 ± 0.39, 11.03 ± 1.36 and 10.69 ± 1.29 g/dl, respectively. A significant decrease was only observed between patients with metastatic breast cancer and normal control females (P=0.010).
The mean WBC counts in normal females, patients with benign breast lesions, patients with non-metastatic breast cancer and patients with metastatic breast cancer were 6.42 ± 1.33 , 8.32 ± 1.65 ,6.79 ± 3.50, 6.43 ± 2.31 (×103cell/µL), respectively. A significant increase was observed in patients with benign breast lesion when compared with normal control females (P=0.015). Also a significant decrease was observed in patients with non metastatic breast cancer (p=0.003) and metastatic breast cancer (p=0.028) when compared with patients having benign breast lesion.
The pathological diagnosis of breast lesions depended on fine needle aspiration and tissue biopsy including either excision biopsy or mastectomy. Tumor tissue sections were stained by haematoxylin & eosin (H&E) for histopathological diagnosis. All breast cancer patients were invasive ductal carcinoma except for three of the non-metastatic group were invasive lobular carcinoma.
The clinical grades (GI, II and III) of non-metastatic patients were diagnosed in 1, 23 and 6 cases, respectively. The corresponding grades of metastatic breast cancer patients were diagnosed in 2, 23 and 5 cases, respectively.
Immunohistochemical analysis of breast cancer tissue sections for ER and PR revealed that ER+/PR+ expression was observed in 26 cases (86.7%) and 18 cases (60%) of patients with non-metastatic breast cancer and those with metastatic breast cancer, respectively. ER-/PR- expression was observed in 2 cases (6.7%) and 7 cases (23.3%) of non- metastatic and metastatic breast cancer patients, respectively. ER+/PR- expression was observed in 1 case (3.3%) and 5 cases (16.7%) of non metastatic and metastatic breast cancer patients, respectively. ER-/PR+ expression was observed only in 1 case (3.3%) of patients with non-metastatic breast cancer.