Introduction. Radiation therapy for oligometastatic non-small cell lung cancer (NSCLC) showed overall survival (OS) benefit in phase II clinical trials, with stereotactic body radiation therapy (SBRT) being the main modality for distant metastases. This study aimed to assess the benefit of consolidative irradiation of the primary lesion in patients with partial response or stationary disease after first-line therapy, regardless of their metastatic burden. Material and methods. Stage IV NSCLC patients without progressive disease after initial systemic therapy were randomly assigned to arm 1 (consolidative primary radiotherapy 45Gy/15 fractions followed by standard treatment) or arm 2 (standard treatment). The primary endpoint was progression-free survival (PFS), and the secondary endpoints were OS and toxicity. Results. Between September 2020 and January 2023, 75 patients were randomized: 37 to the radiotherapy arm and 38 to the control arm. The median follow-up was 13.50 months (4.50-35.93). Median PFS was 15.37 months in the radiotherapy group versus 10.93 months in the control group (univariate HR = 1.99; 95% CI 1.16-3.41; p = 0.012). Median OS was 18.30 months versus 13.73 months, respectively (HR = 1.84; 95% CI 0.98-3.46; p = 0.057). Except for one patient in the radiotherapy group who experienced grade 3 dysphagia, no grade 3 or higher toxicities were noted. Conclusions. Primary consolidative radiotherapy in metastatic NSCLC after standard systemic treatment added a benefit for patients who had stationary disease or showed partial response to standard systemic treatment.

Worldwide, female breast cancer (BC) has surpassed lung cancer as the most commonly diagnosed cancer. Early diagnosis of cancer recurrence can provide substantial benefits for BC patients who are at high risk of relapse. We aimed to investigate the role of ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA as potential diagnostic markers in BC patients and as markers for early prediction of recurrence. Fifty BC patients (10 patients showed recurrence), 26 BBD patients and 22 healthy controls were included. Real-time q-PCR was used to measure the concentration of ALU 247 and ALU 115 in plasma then cfDNA integrity index was calculated. "ECLIA" was used to measure the concentration of CA15-3 and CEA in serum. Our results showed significant higher levels of ALU 247, ALU 115, CA15-3 and CEA in BC patients in comparison to healthy controls (P=0.02, 0.008, <0.001 and < 0.001 respectively). Also, cfDNA integrity index was higher in BC patients in comparison to healthy controls but statistically insignificance (p = 0.46). In recurrent BC patients; ALU 247, ALU 115, cfDNA integrity index, CA15-3 and CEA levels were higher compared to non-recurrent BC patients but with no statistic significant (p = 0.46, 0.59, 0.09, 0.85 and 0.84 respectively). This may result from the short period of follow up (1-2 years) and the relatively small sample size due to exclusion of patients with chronic diseases or inflammation as well as those who received therapy or post-surgery. By using the ROC curve, the sensitivity of ALU 247, ALU 115, CA15-3 and CEA for discriminating BC patients from BBD patients and healthy controls was 79%, 79.2 %, 76.0 % and 88.0 % respectively. This study suggested that ALU 247, ALU 115, CA15-3 and CEA could be promising non-invasive markers of BC for diagnosis and early prediction of recurrence after validation in largescale future studies.

BACKGROUND:Serine-Arginine (SR) proteins are a conserved family of proteins involved in RNA splicing and are reported to be over-expressed in multiple cancers. The aim of the study is evaluation of the expression of Serine arginine protein kinase 1 (SRPK1) and Minichromosome maintenance protein 2 (MCM2) in epithelial ovarian cancer (EOC) and their correlation with clinicopathological features, response to therapy, progression-free survival (PFS), and cancer-specific survival (CSS). METHODS:This study was carried out on surgical specimens of 65 patients diagnosed with EOC which were submitted to immunohistochemical staining by SRPK1 and MCM2 antibodies. RESULTS:About 89.2% of cases showed SRPK1 expression and its high expression was significantly associated with type II tumors and advanced stage. All cases showed nuclear immunoreaction for MCM2 with high expression in 49.2% of cases. There was a significant relationship between high values of SRPK1 H-score and percentage of MCM2. Postmenopause, type II pathology, advanced stage, absence of complete response to the treatment, resistance to platinum-based chemotherapy, and surgery done by a general surgeon were the factors affecting PFS. Response to treatment and platinum sensitivity were the most independent factors affecting patients' PFS. The factors associated with shorter CSS were suboptimal debulking, advanced stage, absence of complete response to the treatment, platinum resistance, and high SRPK1. High SRPK1 expression and platinum sensitivity were the independent factors affecting patients' CSS. CONCLUSIONS:SRPK1 is an unfavorable biomarker in EOC patients because of its association with aggressive histologic type, advanced International Federation of Gynecology and Obstetrics (FIGO) stage, and worse survival. SRPK1 could promote the proliferation of EOC by up-regulation of MCM2.

Purpose/Objective The aim is to evaluate impact of vitamin D supplementation on oral mucositis in patients with head and neck cancer patients receiving radiotherapy with or without chemotherapy and to assess its effect on response to treatment. Material/Methods This is a prospective randomized clinical study conducted on sixty eight patients diagnosed as head and neck cancer that would receive either radiotherapy alone or concurrent chemo-radiotherapy at clinical oncology and nuclear medicine department, Menoufia university. Intervention group vitamin D prescribed. Control group :without vitamin D. All the patients were examined clinically weekly after the start of radiotherapy for WHO mucositis score. Response to treatment was assessed according to revised RECIST guideline (version 1.1) after 2-3 months end of treatment. Results Vitamin D supplementation reduced oral mucositis in head and neck cancer patients receiving radiotherapy with or without chemotherapy with significant p-value < 0.001 at week one, two, three, four, five, six and p-value was 0.042 at seventh week. Skin toxicity, taste changes and dysphagia were significantly better in intervention arm than control arm with significant P-value at week one, two, three, four, five, six and seven (0.011, 0.16, 0.001, <0.001.0.001*5*, 0.001 and 0.121 respectively). Response to treatment was better in intervention arm with significant p - value <0.001. Conclusion This study demonstrates that vitamin D administration had beneficial effect on reducing oral mucositis and other complications like skin toxicity, taste changes and dysphagia during radiotherapy with or without chemotherapy in head and neck cancer patients. It also improved response to treatment.

Assessment of ADC kinetics at regular intervals throughout RT is potentially able to predict the response to RT and oncologic outcome. Further studies with larger cohorts and multi-institutional data are needed for validation of our results.

ObjectiveThis study aims to assess the effect of natural killer (NK) cells and natural killer T (NKT) cells on response to imatinib (IM) therapy in patients with chronic myeloid leukemia (CML).BackgroundNK cells and NKT cells play a vital role in innate immunity against tumors. NKT cells recognize tumor cells by receptor-ligand interaction. After contact with the ligand, NKT cells activate NK cells through inflammatory cytokines [interferon-gamma (IFN-γ) and interleukin 2].Patients and methodsA total of 48 newly diagnosed patients with CML (chronic phase) were included. They were followed up for 1 year after the start of IM therapy and were categorized into IM-responder patients with CML (n = 23) and IM-resistant patients with CML (n = 25). Flow cytometry was used to measure NK and NKT cells. Serum levels of IFN-γ were determined by enzyme-linked immunoassay.ResultsWe found that NK cell% and NKT cell% were increased in the IM-responder group after 1 month of IM therapy. IFN-γ was increased at both presentation and 1 month after the start of IM therapy. Major molecular response was achieved earlier in the IM-responder group, with increased NK cell%, absolute count of NK cell, and IFN-γ.ConclusionWe conclude that NK cells have a critical role in the response of patients with CML to IM therapy and are a predictor of major molecular response in patients with CML.

Breast cancer (BC) is the most common malignancy in female individuals worldwide. It constitutes about 38.8% of all malignant tumors among Egyptian female individuals. Neuropeptide Y1 receptor (NPY1R) is one of the most abundant peptides in the central and peripheral nervous systems of mammals. It has been found to promote proliferation, vascularization, and stimulate migration in several cell types and tissues and some types of tumor. This the first immunohistochemical study to evaluate the expression of NPY1R in BC and its correlation with clinicopathologic parameters and patient survival. This study included 92 patients with BC. Immunohistochemical staining for NPY1R was done on paraffin-embedded formalin-fixed tissue sections. Statistically significant increases in NPY1R expression was seen in malignant (46/92; 50%) versus non-neoplastic tissue (12/29; 20.7%) (P<0.001). The receiver operating characteristic curve showed that NPY1R is a poor diagnostic test for BC (P<0.001, area under the curve=0.686) in breast tissue. Membranous was the most common pattern of positivity in carcinoma cases (24/46; 52.2%). Statistically significant associations were found between positive NPY1R expression and the presence of metastatic disease (P<0.001), clinical stage (P=0.0003), perineurial invasion (P=0.003), estrogen receptor expression (P=0.004), molecular subtype (P=0.015), Nottingham Prognostic Index risk group (P=0.04), radiotherapy treatment (P=0.01), hormonal treatment (P=0.015), and type of endocrine therapy (P=0.011). Although no significant association was detected between NPY1R-positive and NPY1R-negative cases regarding overall survival and progression-free survival, cases with non-nuclear (membranous+cytoplasmic) expression showed near significantly shorter survival (P=0.063). This study shows that NPY1R was identified in about 50% of malignant BC cases. Its expression correlates with some features of the aggressive disease being associated with metastasis, perineurial invasion, advanced stages, and poor Nottingham Prognostic Index. This suggests a potential prognostic role of NPY1R in BC. Non-nuclear expression of NPY1R seems to be more important in terms of prognosis of BC.

Objective The objective of this study was to add to the scope of the role of vascular endothelial growth factor (VEGF) +936C/T gene polymorphism in the prognosis of B-cell chronic lymphocytic leukemia (CLL) in Egyptian patients. Background CLL is a common lymphoid malignancy that has a highly variable clinical course. Several studies have targeted to determine the high risk of disease progression; VEGF-mediated angiogenesis is one of the most vital regulators of angiogenesis and vascular permeability, which can contribute to the pathogenesis of B-CLL. Patients and methods This prospective case–control study was conducted on 30 patients of CLL and 20 age-matched and sex-matched healthy individuals as a control group from January 2016 to January 2018. All patients were subjected to full history taking, clinical examination, and laboratory investigations. Genotyping of VEGF + 936C/T (rs3025039) single nucleotide polymorphism was done using PCR-restriction fragment length polymorphism method. Results VEGF + 936C/T gene polymorphism showed no statistically significant differences in the distribution of the genotypes and allele frequencies between patients and controls. No significant relation was found between genotype distribution and sex, age, somatic hypermutation, hemoglobin, total leukocytic count, and absolute lymphocytes; however, TT genotype and recessive genetic model (CT + CC) revealed a significant relationship with the platelet count in patients with CLL (P = 0.014). A statistically significant relationship was depicted between TT genotype and recessive genetic model (CT + CC) and poor prognostic markers such as lactate dehydrogenase, β2 microglobulin, and modified Rai staging system (IV). Conclusion VEGF + 936C/T gene polymorphism can predict poor prognosis in patients with CLL.

The first confirmed case of coronavirus disease 2019 (COVID-19) in Egypt was reported on 14 February, 2020. Menoufia Clinical Oncology Centre is at the forefront of delivering care to patients with cancer during this public health crisis in Menoufia Governorate, Egypt. This article highlights the unique circumstances and challenges of cancer treatment during this global pandemic and the importance of organisational structure, preparation and a shared vision for continuing to provide cancer treatment to patients in the face of uncertainty and rapid change.

Objective The aim was to study the human programmed cell death 4 (PDCD4) and p53 as diagnostic and prognostic markers in patients with colorectal cancer (CRC). Background CRC is one of the most common cancers. Novel molecules and pathways continue to emerge in the search for improved therapeutic strategies. Patients and methods A total of 120 patients diagnosed with CRC were included and classified based on stage to group 1 (early-stage patients) and group 2 (advanced-stage patients). Moreover, 60 patients diagnosed with benign colorectal polyps were included as a control group (group 3). P53 and PDCD4 antigen levels were measured at presentation, and their relations to patient demographics and clinical features were estimated. Results For PDCD4, area under the curve was 0.889 at cutoff more than 3 ng/ml, with a diagnostic sensitivity of 85.0% and specificity 93.33%, whereas for P53, area under the curve was 1.000 at cutoff greater than 295 pg/ml, with a sensitivity and specificity of 100%. PDCD4 was significantly elevated in group 1 patients compared with group 2 (mean ± SD: 6.9 ± 3.4 vs 1.6 ± 1), with P value less than 0.001. PDCD4 levels were significantly related to tumor grade in groups 1 and 2 (P = 0.041 and 0.011, respectively). P53 levels were higher among patients in group 1 than group 2 (mean ± SD: 2422 ± 692.5 vs 2392.7 ± 680.3, respectively). P53 levels had statistically significant relation with tumor grade in group 2 patients (P = 0.004). Conclusion Both P53 and PDCD4 had diagnostic value. Elevated PDCD4 levels had a positive prognostic value, whereas elevated P53 levels had a negative prognostic value.

Objective The aim was to determine the effect of administration of parenteral l-alanyl-l-glutamine-containing formula on occurrence of treatment-related malnutrition and acute radiotherapy (RT)-related toxicities in patients with head and neck cancer. Background Studies have shown that glutamine-containing nutritional therapy can improve the nutritional status of adult patients with cancer. Patients and methods A total of 40 patients with head and neck carcinoma were randomized to receive either parenteral l-alanyl-l-glutamine-containing formula (0.4 mg/kg) during the first 2 weeks of RT (with or without chemotherapy) or placebo. Nutritional assessment was done for all patients at diagnosis and on weekly basis till end of treatment using subjective global assessment tool and anthropometric measures. Treatment-related toxicity was reported and graded. Quality of life (QoL) was assessed using Functional Assessment of Cancer Therapy for patients with head and neck cancer. Results There was a significant difference between the studied groups regarding subjective global assessment tool score from third week till 7th week (P = 0.019, 0.005, <0.001, <0.001, and 0.021, respectively). Low BMI was more frequent in group 2 patients. Conversely, severe weight loss was significantly different between both groups starting from third week (P = 0.020, 0.010, 0.004, 0.031, and 0.044). There was higher frequency and severity of acute RT toxicities in group 2 patients. There was a significant difference between the two groups regarding QoL as well (P = 0.005). Conclusion l-alanyl-l-glutamine nutritional supplement resulted not only in better nutritional status but also in improved treatment tolerance and QoL.

Accumulating evidence has revealed that livin gene and BCL-2 modifying factor (BMF) gene are closely associated with the initiation and progression of colon carcinoma by activating or suppressing multiple malignant processes. Those genes that can detect colon - cancer are a promising approach for cancer screening and diagnosis. This study aimed to evaluate correlation between livin, BMF and p53 genes expression in colon cancer tissues of patients included in the study, and their relationship with clinicopathological features and survival outcome in those patients. In this study, 50 pathologically diagnosed early cancer colon patients included and their tissue biopsy with 50 matched adjacent normal tissue, and 50 adenoma tissue specimens were analyzed for livin gene and BMF gene expressions using real time PCR. The relationship of those genes expressions with clinicopathological features, tumor markers, Time to Progression and overall survival for those patients were correlated in cancer colon group. In this study, there was a significant a reciprocal relationship between over expression of livin gene and down regulation of BMF and p53 genes in colon cancer cells. Livin mRNA was significantly higher, while BMF and p53 mRNA were significantly lower in colorectal cancer tissue compared to benign and normal colon tissue specimens (P < 0.001), however, this finding was absent between colon adenomas and normal mucosa. There was a significant association between up regulation of livin and down regulation of BMF and p53 expressions with more aggressive tumor (advanced TNM stage), rapid progression with metastasis and decreased overall survival in cancer colon patients, hence these genes can serve as significant prognostic markers of poor outcome in colon cancer patients. This work highlights the role of livin, BMF and p53 genes in colorectal tumorigenesis and the applicability of using those genes as a diagnostic and prognostic markers in patients with colon carcinoma and as a good target for cancer colon treatment in the future.

Papillary thyroid carcinoma (PTC) is the most common thyroid cancer with multiple risk factors including exposure to ionising radiation. Oestrogens contribute to papillary carcinoma development by promoting cell proliferation and invasion of mutated epithelial follicular cells. The present study aimed to assess ER-α and PR expression in PTC and to correlate their expression with the clinicopathological parameters in this cancer. This study included 62 primary and six metastatic papillary thyroid carcinoma cases. Nineteen and 38.7% of primary PTC cases showed positive nuclear expression for ER and PR, respectively. Metastatic cases showed 66.7% positive ER expression and all were negative for PR. Oestrogen receptor expression showed significant higher positivity in metastatic compared to primary PTC (p = 0.02) and it was significantly associated with primary PTC associated with thyroiditis (p = .002). Progesterone receptor expression was significantly associated with old age in primary PTC (p = .003) and it showed significant coparallel expression with ER (p = .000). Oestrogen and progesterone receptors expressed in papillary thyroid carcinoma opening the door for further studies to verify if those patients could benefit from hormonal therapy. Oestrogen receptor seems to have a role in metastatic process of PTC as malignant cells express it in metastatic more than primary site. The presence of lymphocytes in the stroma may promote ER expression in adjacent PTC, necessitating further studies on PTC cases associated with Hashimoto thyroiditis to verify this assumed relationship.

ObjectiveTo study p53 codon 72 polymorphism in relation to cytogenetic response to imatinib treatment in patients with chronic myeloid leukemia (CML).BackgroundP53 polymorphism involves the substitution of an arginine for a proline at codon position 72. Many studies have investigated a genetic link between this variation and response to treatment in cancer.Patients and methodsThis study was conducted on 54 CML patients presented to the Clinical Oncology Department, Menoufia University during the period from June 2013 to April 2015. They were classified according to their cytogenetic response to imatinib therapy into 40 CML patients, cytogenetic responders to imatinib and 14 CML patients who are cytogenetic nonresponders to imatinib. Patients were genotyped for p53 codon 72 polymorphism using PCR. Follow up of the patients should be done after 3, 6, 9, 12, and 18 months after diagnosis, and was done by complete blood count, conventional cytogenetic, and fluorescence in-situ hybridization.ResultsAge, sex, hematologic, and cytogenetic response to imatinib in CML patients did not differ significantly among p53 codon 72 genotypes (arg/arg, arg/pro, and pro/pro) (P = 0.44, P = 0.45, and P = 0.11, respectively). P53 codon 72 polymorphism did not significantly alter the risk to imatinib cytogenetic unresponsiveness (P = 0.9221).ConclusionIt could be concluded that p53 codon 72 polymorphism is not associated with imatinib unresponsiveness in CML.

Background: The objective of the study was to compare the levels of preoperative thyroglobulin (TG), thyroid stimulating hormone level (TSH), FT3, FT4 and TG Ab among 50 malignant and 50 benign thyroid swellings. Papillary thyroid cancer (PTC) is the most common malignancy in thyroid gland. TG antibodies (Ab) occur in around 20% of patients with papillary thyroid cancer (PTC), and the presence of TG Ab complicates the follow-up of these patients because TG-Ab interferes with the assay of serum TG7.Methods: A prospective and retrospective study conducted on 100 patients with thyroid nodule diagnosed by neck ultrasound and confirmed by histopathological evaluation in Faculty of Medicine, Menoufia University Hospital, Egypt, during January 2017 to July 2019. History taking, levels of TG, TSH free T3, free T4 and TG Ab, neck ultrasound or CT and pathological evaluation were done.Results: There were statistically significant differences between malignant and benign thyroid swellings regarding, TG level, TSH and T4 level. Also, there was statistically significant difference between the level of TG and tumor recurrence (p=0.01). While, there was no statistical significance between focality, staging, lymph node status, capsular invasion, lymphovascular embolization, and evidence of hashimoto thyroiditis and the level of TG.Conclusions: Preoperative serum TG concentration is a useful marker for predicting the presence of initial distant metastasis of PTC and tumor recurrence. TSH level considered an important prognostic factor for papillary thyroid cancer patients.

Background:Diffuse large B cell lymphoma (DLBCL) accounts for approximately a third of all NHL and is the most common lymphoma subtype in all parts of the world. Advances in DNA array has resulted in further subclassification of DLCBL into germinal center type and activated B cell type (ABC). Activated B cell type has a worse prognosis than germinal center typeAims:To assess the role of intensified chemotherapy for patients with activated B cell type of DLBCL if it would result in better outcome. Primary end point is response rate and secondary end points are PFS and toxicity, OSMethods:This is a randomized phase II study done on 82 patients. Cases are randomized into two arms. Control arm received R‐CHOP (47 patients) and test arm received R‐CHEOP (35 patients). All cases are tested for BCL‐6, MUM‐1 and CD10 to confirm being of ABC type according to Hans algorithm. GCSF was used for prophylaxis in the test arm in the form of daily 1 vial of neupogen for 3 days after the cycle. Evaluation is done by Cheson et. al. criteria. Toxicity was described according to CTCAE V4Results:Both groups were comparable as regard age, gender, performance status, stage and LDH. Median age was 52 years for the control arm and 46 years for the test arm. Results are analyzed at a median follow up of 15 months. Complete remission at end of treatment was 70.2% for the control arm and 91.4% for the test arm (p = 0.019) while interim assessment showed 58% median tumor shrinkage for the control arm and 79% for the test arm (p < 0.001). Median PFS was 25 months for the control arm and not reached for the test arm (p = 0.022) while median overall survival was 28 months for the control group and not reached for the test arm (p = 0.145). At one year of follow up, overall survival was 74.46% for the control arm and 91.4% for the test arm. Toxicity was comparable in both groups regarding neutropenia (p = 0.356), oral mucositis (p = 0.419), diarrhea (p = 0.54), vomiting (p = 0.504), thrombocytopenia (p = 0.308), anemia (p = 0.453), neuropathy (p = 1)Summary/Conclusion:R‐CHEOP showed more tumor shrinkage than R‐CHOP in activated B cell lymphoma with comparable toxicity. PFS was better in the first year of follow up but more time is needed to calculate mature survival dataimage

Background: Left-sided breast cancer radiation therapy has been associated with an increased risk of major coronary events. There is evidence demonstrating that the increase is proportional to mean heart dose. Deep Inspiration Breath Hold (DIBH) is a radiation therapy technique that has shown significant dose reduction to the heart and lung in hypofractionated radiotherapy of adjuvant left-sided breast cancers. This study explores the potential benefit of utilizing a DIBH technique to reduce heart and ipsilateral lung doses. Methods: This study was done on 65 patients with adjuvant left breast cancer. Patients are coached and asked to voluntarily hold their breath. For each patient, using Computed Tomography simulator machine, two CT scans corresponding to free breathing (FB) and vDIBH were acquired during simulation. Using Monaco treatment planning system FB and vDIBH plans were generated for each patient. All patients were treated on linear accelerator utilizing a vDIBH technique. 40.05 Gy in 15 fractions was prescribed. The evaluating parameters are target coverage; the volume of ipsilateral lung received 20 Gy (V20); mean heart dose (MHD) and volume of heart received 25 Gy (V25). All patients followed an offline portal imaging protocol, where the patients were imaged on day 1-3 and then weekly. Results: The comparing result shows there is a significant reduction in ipsilateral lung and heart dose statistics for vDIBH compared to FB plans without compromising the target coverage. For ipsilateral lung, the V20 was reduced by 15% with vDIBH comparing with FB. The volume of the heart receiving >25 Gy was reduced 20% and MHD was reduced by 18%. These reductions are considered to be statistically significant. The vDIBH mean reproducibility was 2mm (range 1- 4 mm) in antro-posterior direction. Conclusions: Voluntary DIBH technique is successfully implemented and is an important tool for cardiac sparing and has been reproducibly associated with a reduction of mean heart dose. This is a benefit for those patients with left-sided breast irradiation and also has been shown to decrease dose to the lungs. Legal entity responsible for the study: Academic Group. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Background Cystectomy is the primary treatment of muscle-invasive urothelial carcinoma, but it is associated with many complications and affects patients' quality of life. Chemotherapy is an alternative modality, but it may not give the expected response. This arouses the need for markers that help to predict the response to chemotherapy. Human epidermal growth factor receptor 2 (HER2-neu), S-phase kinase associated protein 2 (SKP2), and hypoxia-inducible factor-1 (HIF-1) regulate cell cycle progression, tumor adaptation to hypoxic environment, and response to chemotherapy. Aim This study aimed at evaluation of HER2-neu, SKP2, and HIF-1 expressions in muscle-invasive urothelial carcinoma and investigated the association between their expressions and tumor response to chemotherapy. Materials and methods A total of 100 specimens from patients with nonmetastatic muscle-invasive urothelial carcinoma were collected at the pathology Department, and the selected patients received the treatment and follow-up at Clinical Oncology and Urology departments, Menoufia University. HER2-neu, SKP2, and HIF-1 expressions were evaluated using immunohistochemical techniques. The patients received chemotherapy followed by cystoscopic examination. Bladder biopsy was examined to determine tumor response. Results A significant association was found between partial tumor response to chemotherapy and HER2-neu, SKP2, and HIF-1 positive expression (P=0.004, 0.029, and 0.004). SKP2 expression was significantly associated with low apoptotic count and high mitotic one (P=0.008 and 0.01), whereas HIF-1 expression was significantly associated with necrosis (P=0.008). A statistically significant association was found between SKP2 and HR2-neu expression (P=0.018) and between SKP2 and HIF-1 expression as well (P=0.013). Conclusion This study showed that evaluation of HER2-neu, SKP2, and HIF-1 expression can predict poor response to chemotherapy in muscle-invasive urothelial carcinoma and help in selecting patients who will benefit from chemotherapy. In addition, target therapy against these markers can be effective in treatment.