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العنوان
Immunohistochemical expression of autophagy-related marker (LC3B) and stem cell marker (CD44) in molecular subtypes of breast cancer /
المؤلف
Sayed, Shimaa Gamal.
هيئة الاعداد
باحث / شيماء جمال سيد
مشرف / محمد جلال
مناقش / حسين عبدالمنعم
مناقش / سناء سطوحى
الموضوع
Breast cancer (BC).
تاريخ النشر
2022.
عدد الصفحات
135 p. ;
اللغة
الإنجليزية
الدرجة
ماجستير
التخصص
أمراض الدم
الناشر
تاريخ الإجازة
1/8/2022
مكان الإجازة
جامعة أسيوط - كلية الطب - Department of Pathology
الفهرس
Only 14 pages are availabe for public view

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from 150

Abstract

BC represents a big challenge for public health and has made as nuisance for people who suffered from this disease. It is the first cause of global cancer incidence in females. BC is the second most common cause of cancer-related deaths in women worldwide as the American Institute for Cancer Research (AICR) reported 18 million newly diagnosed cancer cases worldwide in 2018. According to records from NCI, BC represents 18.9% of total cancer cases among women. BC is a complex heterogeneous disease. This heterogeneity is hypothesized to be a function of BCSCs. BCSCs are a small subpopulation of cells, having the ability to self-renew and differentiate into the entire tumor. CD44 is one of the main markers used to investigate it. Activities of BCSCs are maintained by induction of autophagy. Autophagy is a constitutively active, conserved, catabolic process important for the maintenance of cellular homeostasis in response to cellular stress. LC3B is one of the most specific and widely used biomarkers in study of autophagy. This is retrospective study included Formalin fixed paraffin embedded blocks of fifty BC specimens. These specimens have been obtained from the archived paraffin blocks of Surgical Pathology Laboratories, Assuit University Hospital, Faculty of Medicine and South Egypt Cancer Institute, Assuit University. The H&E stained slides were reviewed to evaluate the histopathological diagnosis, tumor grading, DCIS, presence of LVI and PNI. The fifty specimens were divided into different molecular subtypes (Fourteen specimens were luminal A, eleven specimens were luminal B, eleven specimens were her2 neu over expressing subtype and fourteen specimens were triple negative subtype) based on data obtained from patients medical records in oncology department. The present study evaluated the immunohistochemical expression of both stem cell marker CD44 and autophagy related marker LC3B in different molecular subtypes of IDC/NST, their relation with different clinicopathological criteria, and identify the possible correlation between both markers in the studied groups. As regard to CD44 expression, 92% of specimens showed positive CD44 expression while 8% of specimens showed negative expression. Then the specimens were divided into high and low expression groups with 50% of specimens present in each group. According to LC3B expression, all fifty specimens showed positivity for LC3B in various proportion and different intensity. Finally they were divided into low and high expression groups with 78% of specimens showed high expression and 22% showed low expression. Results of this study revealed that stem cell marker CD44 and autophagy related marker LC3B expression are significantly associated with lymph nodal metastasis, advanced pathological stage and with triple negative molecular subtype. As regard to correlation between CD44 and LC3B, statistically significant positive correlation was found between both tumor markers (r=0.366 and p=0.009). There were no relationships between CD44 & LC3B expression and other clinicopathologic parameters such as age of patients, site, and size of tumor, LVI, PNI, TILs and DCIS were found. Both stem cell marker CD44 and autophagy related marker LC3B expression are significantly associated with lymph nodal metastasis, advanced pathological stage and with triple negative molecular subtype of BC. Statistically positive correlation was also found between both tumor markers. There were no relationships between CD44 & LC3B expression and other clinicopathologic parameters such as age of patients, site, and size of tumor, LVI, PNI, TILs, and DCIS were found. These findings suggest that stem cell marker CD44 and autophagy related marker LC3B play a role in the clinical behavior and progression of BC and might be interesting biomarkers and new therapeutic targets particularly for triple negative/basal-like breast carcinoma. Further studies with larger samples are recommended. Tissue microarray and double staining techniques are recommended. Additional correlations with disease progression, disease recurrence, free survival and patient outcome should be done.