Evaluating The Expression Of Insulin Like Growth Factor 1 Receptor Lymphangiogenesis And Proliferation Marker In Breast Cancer Patients In Addis Ababa Ethiopia

Background: Breast cancer (BC) is a heterogeneous disease encompassing distinctrnsubtypes that differ in incidence and prognosis. The identification of correctrndiagnosis, prognostic stratification and treatment effect predictive factors was anrnissue of major debate in cancer management. Better characterization of establishedrnbiomarkers, exploration of novel biomarkers and possible treatment targets arernimportant to improve prognostication and tailored therapy. The availability ofrnmultiple treatment modalities and novel therapeutic targets were based on selectionrnof high and low risk patients can predict the type of systemic or local treatment inrncancer management. rnObjective: This study aimed at evaluating the clinico-pathological factors,rnhistopathological classification of breast cancer and its association with thernexpression of insulin like growth factor 1-receptor.Also, aimed to identify reliablernmarkers that can accurately diagnose lymphangiogenesis for potential marker forrnmetastasis and explore the expression of proliferation marker to predict tumour’srnclinical behaviour. rnMaterials & methods: This is a prospective study included 197 primary operablernbreast cancer study participants who were diagnosed between 2013 and 2015 atrnthree different hospital in Addis Ababa. Clinical/demographic data and related riskrnfactors were obtained by using structured questioners. None of the enrolled studyrnparticipants underwent radiotherapy, chemotherapy or hormone therapy prior to thernextraction of pathological specimens. The samples were collected from mastectomyrnspecimens, fixed in 10% neutral buffered formalin (NBF), and embedded in paraffin.rnDiagnosis was done using classical Hematoxylin and Eosin (H&E) then classifiedrnaccording to WHO recommendation. Modified Bloom Richardson score and TNMrnsystem was used to grade and stage the tumors respectively. Nottingham Prognosticrnindex (NPI) was calculated to predict the prognosis. In addition, immunohistochemicalrnrnstaining was performed on samples to obtain immunoprofile data of rnestrogen receptor (ER), progesterone receptor (PR), and human epidermal growthrnfactor receptor 2 (Her-2/neu) and classify into clinical surrogates for molecularrnsubtype. IGF-1R expression was investigated by using immunohistochemicalrnmethods, in paraffin-embedded blocks samples. The mitotic count was assessed onrnH&E sections in 10 high-power fields (HPF), assigned a mitotic score of 1 to 3 usingrnModified Bloom Richardson criteria and Ki-67 expression was estimated byrnimmunohistochemistry, tumors were classified to three levels of Ki67 index; lowrn(30%) on standard section as proliferationrnindex. The lymphangiogenesis was evaluated by investigating the presence ofrnlymphatic vessel invasion (LVI) and counting of lymph microvessel density (LMVD) byrnimmunohistochemistry using D2-40 monoclonal were correlated with clinicpathologicalrnrnfeatures. IHC expression was evaluated semi-quantitatively in terms ofrnintensity and distribution in cancerous tissues. Frequencies, percentages, chi-squarernand odds ratio were estimated to find out an association between variousrnclinicopathological characteristics and lymph node status using SPSS version 21. rnResult: The mean ± SD age of the study participants was 44.77± 13.6 and thernmedian was 42 years. Most study participants were aged less than 50 years (70.6 %)rnat the time of diagnosis. Among the study group 57.4% were pre-menopausal andrn42.6% were postmenopausal. The duration of symptom before presentation to healthrnfacility with the breast tumour ranged from 2 to 48 months with mean ± SD 18.11±rn13. 2 months. Invasive ductal carcinoma was the commonest (79.2%) histologic typernof breast cancer. Of all study participants, (46.2 %) of them had grade 2, whilern(36.5%) had grade 3 or poorly differentiated tumors. Most study participants (70%)rnpresented with advanced stage (III and IV) and (90%) of them with tumor size morernthan 2cm. The mean and median ages of menarche were 13.65 and 13 years of agernrespectively. Most of the study participants (70%) were categorized in normal bodyrnmass index (BMI) range. Significant variation (p= 0.01) of BMI distribution wasrnobserved in different tumor size. The mean ± SD NPI (Nottingham Prognostic index)rnwas 5.17 ±1.40 (range 2.4- 8.8), which is equivalent to the poor prognostic group.rnOnly 8.1% of the cases were in good prognostic group. Breast cancer pathological rnstage (p=0.02), ER (p=0.005), PR (p=0.01), Ki67 risk category (p

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