Introduction: Triple negative breast cancer (TNBC) is an aggressive form of breast cancer associated with a poor prognosis. No targeted treatment is available for this subtype. Tumor microenvironment (TME) has been increasingly considered a diagnostic and a prognostic biomarker and a therapeutic target for breast cancer. Tumor associated macrophages (TAM) are a pivotal member of TME and have been proposed as potential targets of therapy. Material and Methods: The immunohistochemical expression of CD68+ve TAM was studied in both tumor stroma (TS) and tumor nest (TN) in 50 cases of triple negative invasive ductal carcinoma as well as in 10 control cases of benign breast lesions. Results: The cases were divided into high or low density groups according to the median. The median in CD68+ve TAM in TS was (61.88), while in CD68+ve TAM in TN was (49.88). The expression of CD68+ve TAM in TS was low in 22 cases and high in 28 cases, while its expression in TN was low in 35 cases and high in 15 cases. There was no statistical association between high CD68+ve TAM in TN and different clinicopathological parameters, meanwhile a statistically significant association was found between high CD68 +ve TAM in TS and tumor grade, lymph/vascular invasion and lymph node metastasis. Conclusions: High expression of TAM in TS, but not in TN, is of clinical significance in patients with TNBC and highlights the importance of analyzing the localization rather than merely the presence of TAM as a marker for prognosis and a potential target for future treatment of triple negative breast cancer.
Introduction: The associations between programmed cell death ligand 1 (PD-L1) and the prognosis of various cancers have always been a research topic of considerable interest.However, the prognostic value of PD-L1 in breast cancer patients remains a controversial subject. We aimed to evaluate the role of programmed death-1 receptor and programmed death ligand-1 (PD-1/PD-L1) expressing lymphocytes, monocytes and granulocytes, as potential mechanism of immune escape in breast cancer patients. Also, serum levels of Bcl-2 were analyzed among patients with different stages of breast cancer. Material and Methods: The study was conducted on a total of seventy-five females; fifty-five of them represented the breast cancer females at early (24 females) and advanced (31 females) stages and 20 ages matched female donors represented the control group. Patients were recruited from the Cancer Research and Management Department, Medical Research Institute, Alexandria University. Venous blood samples obtained from all females under study were used for determination of PD-1/PD-L1 expression using flowcytometry technique and measurement of Bcl-2 serum levels using ELISA technique. Results: Significantly higher expression levels of PD-L1 were found in patients with positive lymph node, advanced tumor stage, histological grade II, tumor size T2, ER, PR, Her-2 negativity and TNBC subtype. Whilst a general increase in PD-1 positive expression between the breast cancer patients and control group regarding percentage and MFI of positive PD-1 expressing monocytes and granulocytes. Also, the results showed a highly significant association between PD-1+ and PD-L1+ expression in early and advanced breast cancer patients (p<0.0001). There was a significant increase in the mean of Bcl-2 serum concentration in patients compared to healthy individuals. Finally, the results showed that Bcl-2 serum concentration correlated positively with positive PD-L1+ expressing granulocytes. While the correlation between serum Bcl-2 and PD-1+ expressing lymphocytes, monocytes and granulocytes did not show any statistical significance. Conclusions: Our study suggested that PD-L1 could serve as an important target for antibody based immunotherapies, especially in the TNBC, where treatment options are limited. The direct correlation between PD-L1+ expression and serum Bcl-2 concentration may explore a role of apoptotic machinery in the pathogenesis of breast cancer.
Several prognostic factors are evaluated in the breast carcinoma and there is a need for new markers for better discrimination of the biologic differences in the primary tumor. Epidermal growth factor (EGF) is presumed to play an important role in the local regulation of breast cell proliferation so, the aim of the current study, was to evaluate the serum level of EGF in breast cancer female patients in comparison with other prognostic parameters. It was carried out on fifty-seven females divided into two groups. A control group of twenty healthy women of comparable age and socioeconomic status with a group of thirty-seven breast cancer patients. All females were chosen non-pregnant, not on contraceptive therapy, not previously exposed to radiation, and have no previous history of cancer. To all patients, thorough clinical examination, plain X-ray for the chest and ultrasonography of the abdomen and pelvis were done. Preoperative fine needle aspiration cytology was also done for their breast lumps. In addition, blood samples were collected and analyzed for hemoglobin, fasting serum glucose, urea, and creatinine levels, aspartate and alanine aminotransferase activities, and also the epidermal growth factor level. The breast cancer tissues, removed by surgery, were subjected to histopathologic examination. The median of serum EGF in breast cancer patients group was relatively lower than that in control group but it did not reach the level of significance. No significant differences between the serum EGF levels were found in relation to the change in tumor size, type, grade, and stage. However, there was positive correlations between EGF level and tumor size (r=0.341, p=0.039) and AJCC stages (r=0.354, p=0.032). Also, in patients without lymph node metastasis, there were positive correlations between serum EGF level and both tumor size (r=0.596, p=0.024) and AJCC stages (r=0.596, p=0.024). In patients having lymph node metastasis, there was significant negative correlation between serum EGF level and the number of lymph node metastasis (r=-0.859, p<0.001).There was significant increase in EGF level in patients having lymph node metastasis (3 LN) when compared to patients having no LN metastasis (p=0.004) and its level in patients having (>3 LN) metastasis was significantly decreased than that in both patients having no LN metastasis (p=0.019) and patients having 3 LN metastasis (p<0.001). In addition, EGF level was significantly increased in patients with estrogen receptor (ER) negative than in patients with ER positive (p=0.049). Also, there was a negative correlation between EGF level and ER positivity (r=-0.454, p=0.005). Similar correlation was also found in patients having LN metastasis (r=-0.680, p<0.001). But there was no significant relationship between serum EGF level and the state of progesterone receptor. In conclusion, determination of serum EGF in combination with certain histological parameters could be useful in determining tumor prognosis and in deciding the selection of treatment modality, however...
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