الفهرس 
المقدمةOnly 14 pages are availabe for public view
Abstract
This work aimed at studying the immunohistochemical expression of CD163 in tumor cells of invasive breast carcinoma and pure ductal carcinoma in-situ and peri-tumoral tumor associated macrophages (TAMs) together with evaluation of CD47 expression in tumor cells and their effect on the prognosis of the breast cancer.
The expression was assessed in the invasive group (71 cases with assessment of the ductal carcinoma in-situ adjacent to the invasive component in 19 cases out of the 71 cases), in the pure DCIS group (10 cases) and in the normal control breast tissue group (10 cases). Cases were diagnosed in Pathology Department, Faculty of Medicine, Menoufia University during the period between January 2015 and December 2018. Revision of all submitted breast cancer cases in this period was done. The selection of the studied cases was done meticulously according to inclusion and exclusion criteria.
The data collected from the pathology reports of the invasive carcinoma cases included age of patient which ranged between 31 and 80 years with a mean age of 50 years, the site of the tumor that was mostly upper outer quadrant (UOQ) (53.5%) of left sided breast (54.9%), T stage where advanced stages (stage T3, T4) were seen in (21.1%) of the cases and nodal metastasis where (74.7%) of cases were associated with positive LNs involvement metastasis.
Data concerning ER, PR, HER2neu status and Ki67 values were obtained by re-evaluation of the immunohistochemical stained slides. Regarding the invasive carcinoma cases, 70.4% of our cases were ER positive, 12.7% were PR positive, 39.4% were positive Her2neu expression and 53.5% showed high Ki-67 proliferation index.
The data about the different treatment protocols for the invasive carcinoma cases were collected from the archive of the Oncology department, Menoufia university. 90.1% received adjuvant chemotherapy sequence, 8.5% received metastatic chemotherapy, 38.0% received postoperative targeted therapy, 67.6% received post-operative radiotherapy and 64.8% received hormonal therapy.
The paraffin blocks were serially sectioned and stained with hematoxylin-eosin stain for histopathological examination of histologic type where all the invasive breast cancer cases were IDC-NST, histologic grade where grade II tumors were found to represent the highest percentage (71.8%) of cases, LVI, mitotic count and presence of adjacent DCIS. Regarding the cases of pure DCIS, all the cases were of Ductal Carcinoma In-Situ (DCIS). Additional sections were prepared from the paraffin blocks and were immunostained with CD163 and CD47 antibodies.
CD163 imunohistochemical expression was detected in the tumor cells in (94.4%) of the invasive carcinoma cases and in the tumor cells in all the pure in-situ cases (100.0%). In the comparison done between CD163 expression in the invasive carcinoma group, the control breast tissue group and the pure DCIS group, there was a significant difference between all the groups regarding macrophages infiltration density/ 5 HPFs and macrophages infiltration density categorization (p<0.05) with invasive cases showed the highest TAMs infiltration density.
A statistically significant correlation was found between the high expression of CD163 in the tumor cells of the invasive carcinoma cases and higher tumor grades, advanced T staging, advanced AJCC stage grouping, distant metastasis, poor NPI
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group, ER negativity, the triple negative and Her2neu enriched molecular subtypes (p<0.05).
As regard peri-tumoral TAMs in the invasive carcinoma group, according to the quantitative method (84.5%) of the cases showed high index of TAMs infiltration and according to the semi-quantitative method (43.7%) of the cases showed dense category of TAMs infiltration. A statistically significant association was found in our study between the high TAMs infiltration in the invasive carcinoma cases and the higher histological grade, poor NPI group, ER and PR negativity, the triple negative and Her2neu enriched molecular subgroups (p<0.05).
In the current work, there was a significant association between the high CD163 expression in tumor cells on one side and high TAMs infiltration index and the dense category of TAMs infiltration on the other side in both the invasive carcinoma group and the pure DCIS group.
Assesment of IHC expression of CD47 was done in the malignant epithelial cells in the invasive and pure DCIS groups. In comparison done between CD47 expression in the invasive carcinoma group, the control breast tissue group and the DCIS group, the invasive component showed the highest IRS scoring of CD47 expression. CD47 was detected in the tumor cells in all the invasive carcinoma cases. Over-expression (according to IRS score) was detected in about (51%) of the invasive breast cancer cases. Regarding the pure ductal carcinoma in-situ cases, CD47 was expressed in tumor cells of all the pure in-situ cases (100.0%). According to the IRS scoring system; (40.0%) of the pure in-situ cases showed high CD47 expression. A statistically significant correlation was found between the high CD47 expression in the tumor cells of the invasive carcinoma cases and site of the tumor (lower outer quadrant), higher tumor grades, nodal metastasis, high mitotic index, high NPI scoring, poor NPI group, ER negativity, high Ki-67 values, high proliferative index, Her2neu positivity, the triple negative and Her2neu enriched molecular subtypes (p<0.05). Regarding the relationship between the CD47 expression in the tumor cells and CD163 expression in tumor cells and TAMs in both invasive and pure in-situ groups, there was a significant linear proportional association between CD47 expression in the tumor cells, CD163 expression in tumor cells and TAMs density (p<0.05).
In the univariate analysis by using Kaplan-Meier for the overall survival, shortened overall survival was significantly associated with high CD163 IRS score (p<0.05). Also there was an association between shortened overall survival and high CD47 IRS score and dense category of TAMs infiltration.
In the univariate analysis by using Kaplan-Meier for the disease free survival, shortened DFS was significantly associated with high CD163 IRS score (p<0.05). The Multivariate Cox regression analysis; using (OS) and (DFS) time in months and the co-varieties which showed significant association with both of them; revealed that the high CD163 IRS score showed association (that failed to reach significance) in affecting patients’ overall survival (P=0.08).
Regarding the univariate analysis by using Kaplan-Meier for the overall survival (OS) and disease free survival (DFS) and the relation with the CD163 and CD47
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expression and their effect on the different treatment options: we noted shorter (OS), (DFS) and lower percentage of (End study living cases) were seen in the cases with high CD163 IRS score, high CD47 IRS score and dense category of TAMs infiltration in comparison to the cases that showed low CD163 and CD47 IRS scores and absent/sparse TAMs infiltration even with receiving post-operative chemotherapy, endocrine therapy, targeted therapy and radiotherapy.