Ranih Zakaria Soliman

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Research

Significance of Toll-like Receptor 4 ( TLR4 )& Liver Fatty Acid-binding Protein (L-FABP) Expression in Hepatocellular Carcinoma An Immunohistochemical Study

Authors : Eman El-Gendy1; Ranih Zakaria1; Taghreed Abd Elsamee1; Hala Agina1; Reda El badawy

Abstract :Back ground: Persistent inflammatory conditions can induce tumorigenesis . It is therefore very important to explore the molecular mechanisms involved in progression from chronic hepatitis to cirrhosis to HCC - to identify factors useful for the development of effective therapies that improve patient survival. Aim of the study: Evaluation of TLR-4 and L-FABP expression in cases of chronic hepatitis, cirrhosis and HCC and correlate them with clinicopathological parameters. Methods: A retrospective, immunohistochemical study was performed on 50 liver cases; 32 cases of HCC, 10 cases of chronic hepatitis C, and 8 cases of cirrhosis. Results: There was statistical significant increase in TLR-4 expression in HCC than both chronic liver hepatitis and cirrhosis (P<0.05). There was positive statistical significant correlation between TLR-4expression and size & grade of HCC (P<0.05) . There was highly statistical significant decrease in L-FABP expression in HCC than both chronic liver hepatitis and cirrhosis (P< 0.001). Conclusion: TLR-4 has a role in hepatocarcinogenesis as TLR-4 expression increased with progression from chronic hepatitis to cirrhosis to HCC. Increased TLR-4 expression associated with large tumor size and higher grade of HCC, so it may serve a tool for prognosis of HCC. L-FABP expression decreased with progression from chronic hepatitis to cirrhosis to HCC. So its downregulation may contribute in pathogenesis of HCC.

Keywords : TLR-4; L-FABP; Hepatocellular carcinoma; chronic hepatitis C

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Significance of Insulin-Like Growth Factor II Mrna-Binding Protein 3 (IMP3) Expression in Selected Thyroid Lesions

Authors : Taghreed Abd ElAziz; Ranih Amer; Omnia Bassyoni; Hanan Ahmed*

Abstract :Background: Differentiation of benign from malignant follicular thyroid lesions remains difficult and the ability of molecular markers to differentiate between them still unclear. The aim of this study was to evaluate the usefulness of IMP3 expression to distinguish benign from malignant thyroid lesions. Methods: This is a retrospective study upon selected 57 thyroid lesions designated as; 7 cases of Hashimoto thyroiditis (HT), 10 cases of hyperplastic nodules (HN), 15 cases of follicular thyroid adenoma (FTA), 13 cases of conventional papillary thyroid carcinoma (PTC), 6 cases of follicular variant of papillary thyroid carcinoma (FV-PTC), and 6 cases of follicular thyroid carcinoma (FTC). Immunohistochemistry was applied on formalin-fixed, paraffin-embeded tissue blocks using IMP3. clinicopathological data were reviewed from patients' pathological reports and correlated with IMP3 expression. Results: IMP3 positivity was seen in1/7 cases (14.3%) of HT, 2/10 cases (20%) of HN, 4/15 cases (26.7%) of FTA, 12/13 cases of PTC, and in all (100%) FV-PTC & FTC cases. IMP3 staining was significantly increased from normal thyroid tissue up to malignant tumors (P<0.01). IMP3 showed 96% sensitivity and 78.1% specificity for malignant tumors. IMP3 expression was positively correlated with grade and tumor size in malignant cases (P<0.05). No significant correlation was found in IMP3 expression with patient age, sex, capsular invasion, lymphatic/vascular invasion, lymph node metastasis, distant metastasis and TNM stage. Conclusions: IMP3 is a potential diagnostic marker for thyroid cancer and can be a promising marker for distinguishing benign from malignant follicular patterned thyroid lesions.

Keywords : IMP3, Thyroid

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Significance of silent mating type information regulation 2 homolog 1 and claudin 4 expression in gastric carcinoma and precursor lesions: an immunohistochemical study

Authors :Emara, Nashwa M.Amer, Ranih Z.Elsadek Attia, Khaled M.Rashad, Heba M.Elseady, Adel Z.Elbalshy, Abd El-Latif M.

Abstract :Background Silent mating type information regulation 2 homolog 1 (SIRT1) and claudin 4 have been implicated in tumorigenesis in many cancers, but their significance in gastric carcinoma (GC) remains unclear. The aim of this study was to assess their possible significance in GC. Materials and methods Immunohistochemistry was performed to examine the expression of SIRT1 and claudin 4 in 68 cases of GC and three adjacent precursor lesions (chronic gastritis, intestinal metaplasia, and dysplasia). Statistical analysis methods were used to evaluate the relationship between SIRT1 and claudin 4 and various clinicopathological parameters. Results SIRT1 and claudin 4 were found highly expressed in GC. The two markers significantly correlated with depth of tumor invasion, distant metastasis, and TNM stage. SIRT1 was positively correlated with advanced tumor grade, whereas claudin 4 was inversely correlated with it. No significant correlation between SIRT1 and claudin 4 was detected. Conclusion The results suggested that both SIRT1 and claudin 4 might be involved in gastric carcinogenesis. The more advanced the TNM GC stage, the higher the expression of SIRT1 and claudin 4. This suggests their possible role in GC progression.

Keywords : gastric carcinoma, SIRT1 and claudin 4

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The expression of Hypoxia-inducible factor-1 in astrocytoma

Authors : Samah Ibrahim, Magda Hamed Bakr, Eman Saad Omar, Ranih Zakaria, Rasha Mohammed Elsawi

Abstract :Objective: Evaluation of Hypoxia-Inducible Factor-1 (HIF-1) expression in astrocytictumors of various grades to assess its prognostic role in astrocytoma. Material and Methods: This retrospective study included 40 cases of astrocytoma. The materials included archival formalin fixed paraffin embedded blocks from Pathology Department, Faculty of Medicine, Benha University during the period of 2010 to 2013. All cases were H & E stained and immunohistochemically stained by HIF-1. HIF-1 expression was estimated using immunohistochemistry under the light microscope as nuclear brown granules. Statistical analysis was performed in all examined groups. Results: All (100%) Grade I astrocytoma cases do not show any HIF-1 expression, while it was observed in 44.4% of Grade II cases, in 50% of Grade III and in 84.6% of Grade IV cases. There was a significant statistical correlation between HIF-1 extent of expression and the grade of astrocytoma (p value <0.05). Additionally HIF-1 expression is statistically correlated with age, three-year disease free survival and recurrence of studied cases of astrocytoma (p-value <0.05). Conclusion: The results of this study suggest that HIF-1 expression may be associated with the development and progression of astrocytic tumors.

Keywords : Hypoxia-inducible factor-1 , astrocytoma

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Assessment of ERBB2 protein expression and gene amplification in urothelial bladder carcinoma by immunohistochemistry and fluorescence in situ hybridization

Authors :Ahlam Abdelmaksoud, Nashwa M Emara, Ranih Zakaria

Abstract :Background: The goal of this study was to investigate ERBB2 (HER2) gene amplification and protein expression in bladder urothelial carcinoma. The HER2 status of 40 patients with transurethral resection or cystectomy was investigated. All cases were analyzed for both HER2 overexpression using immunohistochemistry and HER2 gene amplification using fluorescence in situ hybridization. Eighteen cases had a HER2 score-0 or score-1 (45%), 10 cases had a score-2 (25 %), and 12 cases had a score-3 (30%) with immunohistochemistry. HER2 gene amplification was observed in 16 out of 40 cases (40%). HER2 overexpression and gene amplification were correlated to a high histological grade (P< 0.0001), stage (P< 0.0001) and 5-year survival (P< 0.0001). A good correlation was observed between protein overexpression and gene amplification (p< 0.0001). Conclusion: Those data indicated that ERBB2 genetic abnormalities were associated with the prognosis of bladder cancer. Clinical assessment of ERBB2 amplification may represent an important factor for the development of personalized treatment programs for bladder urothelial cancer.

Keywords :ERBB2 (HER2) gene, urothelial bladder carcinoma, in situ hybridization

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Significance of SIRT1 and Claudin 4 Expression in Gastric Carcinoma & Precursor Lesions: An Immunohistochemical study

Authors : Nashwa M. Emara, Ranih Zakaria, KHALED M. ELSADEK ATTIA, et al

Keywords :claudin 4, gastric carcinoma, silent mating type information regulation 2 homolog 1

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Mean Platelet Volume and Hepatic Stellate Cells Activity as Fibrosis Markers in Egyptian Patients with Chronic Hepatitis C

Authors :Maha Zein, Ranih Zakaria, HATEM S ABD ELRAOUF, Mona Elbehisy

Abstract :Background and Aims: liver biopsy is the gold standard in assessing liver histology and stellate cells activation by specific markers as alpha-smooth muscle actin (a-SMA). However, this procedure is invasive and costly, hence, non invasive tests have been proposed to assess the severity of hepatic fibrosis. Mean platelet volume (MPV) is a laboratory marker obtained from complete blood count (CBC) analyzer in routine clinical practice. The goal of the present study was to investigate whether MPV, hepatic stellate cells activity could be markers for fibrosis in chronic hepatitis C (CHC) patients. Methods: A total of 83 patients with CHC and 20 control subjects were included in this study. MPV was recorded at the time of admission. Activated hepatic stellate cells were identified immunohistochemically using antibody to a-SMA immunostaining in 53 of studied cases of CHC and 10 control samples. The clinical characteristics of chronic hepatitis C patients including demographics, laboratory findings were reviewed and liver biopsies were scored for fibrosis in Early Cancer Detection Unit-Benha University and Pathology De-partment of Faculty of Medicine, Benha University. Results: Statistically significant increase in MPV values was observed in CHC patients (9.006±1.71) compared to healthy controls (8.01±0.97) (p<0.01). MPV values also were higher among patients with severe fibrosis as compared to those with mild fibrosis (9.62±2.34 vs 8.85±1.49) but without statistically significant difference (p=0.098). On the other hand, there is statistically significant correlation between a-SMA expression and stage of fibrosis (p<0.00 1). While, MPV was increasing with increased a-SMA expression but without statistically significant difference (p=0.3). Conclusion: The present study showed that MPV increased in CHC patients with severe fibrosis but MPV is not specific marker for fibrosis in relation to stellate cell activity which is directly correlated with stage of fibrosis

Keywords : Mean Platelet Volume, Hepatic Stellate Cells, Egyptian Patients, Chronic Hepatitis C

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P784 INTERLEUKIN-18 AND ITS GENE POLYMORPHISMS INFLUENCE THE PROGRESSION OF CHRONIC HEPATITIS C

Authors : E.M. Said, M.S. Soliman, M.S. Rashed, A.A. Abo El Azm, R. Zakaria, F.M. Abd El Salam

Abstract :Significance of stem cell marker Lgr5 expression in colorectal carcinogenesis Ranih Zakaria Amer, Nashwa Mohamed Emara, Ghada Abd-Elfattah, Heba Mohamed Rashad, Nehal Saad Zafer Pathology Department, Benha Faculty of Medicine, Benha University Abstract BACKGROUND: Lgr5 (Leucine rich repeat containing G–protein- coupled receptors) also known as G-protein- coupled receptor (Gpr-49). It belongs to the large, G-protein– coupled, 7-transmembrane (7TM) family of proteins. In order to determine whether Lgr5 is a potential marker of cancer stem cells, we investigated Lgr5 expression in normal colorectal mucosa, adenoma and carcinoma and compared the results with the clinicopathological data and prognosis. METHODS: This is a retrospective study carried upon 40 Egyptian patients with different types of colorectal lesions, 6 cases of adenoma and 34 carcinoma (20 cases were cribriform adenocarcinoma, 6 signet ring carcinoma and 8 mucoid carcinoma). Six cases were taken as control from adjacent normal mucosa in patients with intestinal infarction. Lgr5 expression was evaluated by immunohistochemistry in the collected colorectal lesions. RESULTS: Lgr5 was detected as cytoplasmic brown granules with different expression patterns in normal colonic mucosa, adenoma and carcinoma. Lgr5 expression was significantly higher in carcinoma than in adenoma (P<0.05). Statistical analysis revealed a significant increase in Lgr5 expression with progression from normal colon towards carcinoma (P<0.01). A significant statistical correlation was also found between lgr5 expression and stage of colorectal carcinoma including depth of tumor invasion, lymph node metastasis and distant metastasis (P<0.05). CONCLUSIONS: Lgr5 may play an important role in colorectal tumorigenesis and invasion, and may be potential therapeutic target for the treatment of patients with colorectal cancer. It may also be considered as a potential marker for colorectal cancer stem cells (CSCs).

Keywords : P784 INTERLEUKIN-18, GENE POLYMORPHISMS, CHRONIC HEPATITIS C

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Significance of stem cell marker Lgr5 expression in colorectal carcinogenesis

Authors : Kamar, Ghada & Zakaria, Ranih & Emara, Nashwa & Rashad, Heba & Zafer, Nehal

Keywords :stem cell markers, Lgr5, colorectal carcinogenesis

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Evaluation of galectin-3, b-catenin, and nuclear morphometry in different thyroid lesions

Authors :AbdelMaksoud, Ahlam A.AbdElfattah, Ghada A.Amer, Ranih Z.Emara, Nashwa M.

Abstract :This study aimed to evaluate the expression pattern of galectin-3 and β-catenin and assess the nuclear morphometric features of different thyroid lesions in order to investigate their diagnostic significance. Materials and methods Sixty specimens of benign and malignant thyroid lesions, in addition to 10 cases of normal thyroid tissue used as control, were immunohistochemically stained with antibodies against galectin-3 and β-catenin. Hematoxylin and eosin-stained slides were examined using image analyzer Proplus V software. Morphological parameters measured included mean nuclear diameter, mean nuclear perimeter, and mean nuclear area. Results Cytoplasmic immunoreactivity for galectin-3 was strongest in papillary thyroid carcinomas (88.9%), whereas staining was less intense in the follicular variant of papillary thyroid carcinoma and in follicular (60 and 75%, respectively) and poorly differentiated carcinomas (28.6%); it was expressed focally and weakly in follicular adenoma cases and even more weakly in the reactive follicular epithelium of nodular goiter (P<0.5).Membrane β-catenin expression was decreased in only two of 13 (15.4%) adenomas and in 21 of 38 (55.3%) carcinomas (P<0.5). Among carcinomas, reduced membrane β-catenin was associated with progressive loss of tumor differentiation and increased invasiveness (P<0.5).The mean nuclear diameter and the mean nuclear perimeter were higher in undifferentiated carcinomas when compared with other subtypes and were the least for follicular neoplasms. Conclusion Galectin-3 immunostaining and analysis of β-catenin dysregulation may be useful as an adjunct to distinguish benign from malignant thyroid lesions. Quantitative estimation of nuclear features can play a role in assessment of the morphological features and thus help in the diagnosis of thyroid lesions

Keywords : galectin-3, b-catenin, nuclear morphometry, thyroid

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Diagnostic role of AMACR and P63 immunohistochemical expression and their relation with PI-RADS V.2 on Mp-MRI in prostatic lesions

Authors :Ranih Z. Amer, Ahmed A. Torki, Kareem ElAttar

Abstract :Background and Aims: Accurate diagnosis of clinically significant prostate cancer is essential in identifying patients who should undergo treatment with curative intent. Pathological reporting was used as gold standard in assessing prostate histology and immunohistochemistry. However, this procedure is invasive; hence, non-invasive tests have been proposed to assess the severity of prostatic lesion. Multi-parametric magnetic resonance imaging (MRI) of prostate is a major diagnostic tool in cancer detection. Prostate Imaging Reporting and Data System (PIRADS) Version 2 was recently issued by The American College of Radiology. Each PIRADS score, ranging from 1 to 5, corresponds to a clinically significant cancer. This study aimed at comparing the diagnostic accuracy of immunohistochemistry (using anti- AMACR and P63 antibodies) and Mp-MRI with PIRAD 2.0 scoring system in different prostatic lesions. Patients & Methods: A retrospective study carried on 70 patients with prostatic lesions with mean age of 62 years. The patients underwent PR examination, PSA tests, TRU/S, and Mp-MRI prostate and scored by PIRADS scoring system. Immunohistochemistry using anti-AMACR and anti-P63 antibodies was done. Imaging data were correlated with histopathological and immunohistochemical data using SPSS software. Results: AMACR expression was restricted to malignant lesions (Prostatic carcinoma) and HGPIN and was negative in BPH and LGPIN specimens (P0.05). P63 is highly sensitive and specific marker for non-malignant prostatic lesions. There was significant relationship between higher PIRADS score and findings of cancer on pathology (p7) tumors were found in MP-MRI with high PIRADS score (4 or 5), but without statistical significant difference (P>0.05) as 81.8% of low grade (Gleason score 6-7, grade <4) tumors were also found in PIRADS score 4 or 5. Conclusions: Suspicious lesions and benign mimickers of malignancy must be identified by prostate biopsy and confirmed by combination of immunohistochemical markers as p63 and AMACR which is of great adjunct in combating the morphologically suspicious cases to reduce misdiagnosis. PIRADS scoring system is a useful and sensitive tool in suggesting PCa. However, PIRADS criteria alone are not sufficient for determining clinically significant prostate cancer.

Keywords :prostatic carcinoma, AMACR, P63, PI-RADS

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Differential Expression of Autophagy-Related Marker (Beclin-1) in Relation to Clinicopathological Parameters in Different Breast Cancer Molecular Subtypes

Authors : RANIH Z. AMER, SHAIMAA M.N. EL-ZAMLY, HALA A. AGINA and MONA A.M. ABO EL-KHAIR

Abstract :Background: Beclin-1 plays a vital role in the vesicle nucleation in the process of autophagy and has an important role in development, tumorigenesis, and neurodegeneration. Aim of Study: Study the role of beclin-1 and correlate the degree of its expression with available clinic-pathological data in different molecular types of breast cancer. Material and Methods: Immunohistochemistry was per-formed to examine the expression of Beclin-1 different mo-lecular subtypes of invasive ductal carcinoma and correlating it to clinicopathological parameter. Results: The expression of Beclin-1 was decreased in breast cancer in relation to normal tissue. High expression was significantly correlated with tumor grade, distant metas-tasis and stage. All the cases with high Beclin-1 expression were triple negative breast cancer cases. Conclusions: Triple negative breast cancer cases showed the highest tumor stage, grade, distant metastasis and beclin-1 expression suggesting that the overexpression of Beclin 1 may by itself confer an aggressive biological course. It could be a therapeutic target.

Keywords : Autophagy, Beclin-1, Breast Cancer Molecular Subtypes

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Prognostic Significance of Survivin and Nuclear Morphometry in Nasopharyngeal Carcinoma

Authors : RANIH Z. AMER, ADEL Z. EL-SEAIDEY, AHMED E. ELBADAWY, OMNEYA Y. BASUNY and SAMIA A. YOUSSEF

Abstract :Purpose: American Joint Committee on Cancer (AJCC) TNM staging system has been widely used for prognosis prediction of nasopharyngeal carcinoma (NPC) patients. Although NPC patients can be classified according to their clinical stage in this system, their prognosis may vary signif-icantly. Therefore, it is important to search for novel molecular biomarkers, which can help in improvement of the prognostic prediction. So, this study aimed to evaluate survivin expression and assessment of nuclear morphometric features of nasopha-ryngeal carcinoma to investigate their prognostic significance. Material and Methods: Forty nine cases of nasopharyngeal carcinoma (NPC) with clinical follow-up data were collected and expressions of survivin in tumor tissues were investigated by immunohistochemistry (IHC). Nuclear Morphometry was also studied for all cases. Results: Patients’ follow-up revealed 30 cases (61.2%) developed lymph node metastasis, 18 (36.7%) developed distant metastasis, among them 13 (63.3%) died. Survivin expression was significantly correlated with TNM stage of nasopharyngeal carcinoma (NPC). Patients with low survivin expression had better 3-year survival rate than the group with high survivin expression (75% vs. 25%, respectively, p<0.05). Mean nuclear area in cases with low survivin expression was 37.88, which was significantly lower than that in those with survivin over-expression (52.81) (p<0.05). Conclusion: Nasopharyngeal carcinoma cases express high survivin levels, which may play an important role in tumor progression. Survivin over-expression and high mean nuclear area (MNA) were associated with poor prognosis. So, we suggest that determination of tumor survivin expression and MNA may provide valuable predictive informations on NPC patients.

Keywords : Survivin, Nuclear Morphometry, Nasopharyngeal Carcinoma

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Significance of Epithelial cell adhesion molecule (EpCAM-CD 326) and Cytoketain 19 Expression in Hepatocellular carcinoma: An immunohistochemical study

Authors :Abd Ellatif Mohammed Elbashy , Eman Saad Omar, Rania Zakaria Amer, Dina Shehata Elazab, Naglaa Hamed Ibrahim

Abstract :Back ground: Hepatocellular carcinoma (HCC) is the most common primary liver cancer. Globally it is the sixth most common cancer worldwide and the third most common cause of cancer death. In Egypt, HCC constitutes 70.48% of all liver tumors among Egyptians. Liver cancer is the first most common cancer in men and the second in women. One of the postulated models for pathogenesis of HCC is the role of CSCs which are responsible for tumor initiation, maintenance, growth, metastasis, and relapse after therapy. There were several proposed stem cells markers in such as epithelial cell adhesion molecule (EpCAM), CD90, CD13, Cytoketain 19 (CK19), CD133, and CD56. Aim of the study: To evaluate expression of EpCAM and CK19 in cases of chronic hepatitis, chronic liver disease with HCC and hepatocellular carcinoma. In addition, studying the relation between their expression and clinicopathological data. Materials and Methods: A retrospective study was performed on paraffin sections of 81 specimens of liver tissues including 6 specimens of normal liver, 24 specimens of chronic hepatitis C and 51 specimens of HCC, 39 cases of non-tumour tissue adjacent to Hepatocellular (HCC). All sections subjected to: Hematoxylin and eosin stain for histopathological assessment to confirm diagnosis and immunohistochemical staining for evaluation of EpCAM and CK19 expression Results: All cases of studied normal group were negative for EpCAM and CK19 expression. Regarding to EpCAM, There was statistical significant increase in EpCAM expression from chronic hepatitis to adjacent non tumor tissue (chronic liver disease with HCC) then decrease in HCC. There was statistical significant relation between EpCAM with AFP level only. Regarding CK19 expression, There was statistical significant difference between +ve CK-19 hepatocytes in all groups as it is only present in HCC group (3.2±14.2) and between +ve CK19 cells with LPC morphology in all groups as the highest levels in non-tumor adjacent group. There was statistical significant relation between CK19 expression in chronic hepatitis group with activity and fibrosis, while in HCC group, there was statistical significant relation between CK19 expression and AFP level and grade. Conclusion: Stem cells have a role in early hepatocarcinogenesis as EpCAM and CK19 increased in both chronic liver disease with or without HCC and decrease in HCC. Increased CK19 expression associated with higher serum AFP level and higher grade of HCC, so it may serve a tool for prognosis of HCC.

Keywords : EpCAM, CK19, Hepatocellular carcinoma, Stem cells

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Significance of tumor-associated macrophage density and CXCR4 expression in renal cell carcinoma

Authors :Amer, Ranih Z.; Bassyoni, Omneya Y.; Gharib, Tarek M.; et al

Abstract :Objective: Renal cancers are considered immunogenic tumors that are frequently infiltrated by immune cells. Tumor-associated macrophages (TAMs) represent a major leukocyte population, infiltrating tumors, and are associated with poor prognosis. Chemokines and their receptors play an important role in the tumorigenesis of many malignancies. The purpose of this investigation was to assess the immunohistochemical expression of TAMrelated marker CD68 and chemokine receptor CXCR4 and study their correlation with other clinicopathological factors to detect the usefulness of these markers in the diagnosis and prognosis of renal cell carcinoma (RCC). Materials and methods: Immunohistochemical expression of CD68 + ve TAM density and CXCR4 was analyzed in 57 cases of RCC and 10 cases of normal renal tissue. Results: The higher expression of CD68 +ve TAMs was 57.8% and CXCR4 in 59.6% in RCC, which was statistically significantly different from the control group, which showed lower expression (P<0.01 and <0.05),