Publications by authors named "Ola A Harb"

23 Publications

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Forkhead box M1 over-expression and dachshund homolog 1 down-regulation as novel biomarkers for progression of endometrial carcinoma in Egyptian patients.

Contemp Oncol (Pozn) 2021 1;25(2):107-117. Epub 2021 Jun 1.

Clinical Oncology and Nuclear Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: Forkhead box M1 (FOXM1) is considered as a novel anti-cancer target, because it has many essential functions such as mitosis regulation, cell cycle transition, and other carcinogenesis signaling pathways. Dachshund homolog 1 (DACH1) is a member of the Sno/Ski co-repressor family.

Material And Methods: Expression of DACH1 has been detected in many cancers. Patients and pathologic specimens: 50 patients with endometrial cancer (EC) were included in the study: ten specimens of normal endometrium and twenty specimens of endometrial hyperplasia. All samples underwent processing to investigate FOXM1 and DACH1 expression using immunohistochemistry.

Results: FOXM1 expression was detected in EC tissues more than normal endometrium and endometrial hyperplasia tissues ( = 0.001) and 0.01. Increased FOXM1 expression was positively associated with larger tumor size ( = 0.002), high grade ( = 0.004), myometrial invasion, presence of lymph node metastases, higher Federation of Gynecology and Obstetrics (FIGO) stage ( < 0.001), and worse progression-free survival (PFS) and overall survival (OS) rates. The expression of DACH1 was lower in EC cells than normal endometrium and endometrial hyperplasia tissues ( = 0.071) and 0.252. Low DACH1 expression was associated with high grade ( = 0.001), presence of lymph node metastases ( = 0.49), higher FIGO stage ( = 0.022), and unfavorable PFS and OS rates ( = 0.037). We found an inverse association between expression of FOXM1 and DACH1 in EC tissues and in non-neoplastic endometrial tissues ( = 0.007).

Conclusions: FOXM1 over-expression and DACH1 down-regulation in EC were related to poor clinical and pathological parameters and unfavorable prognosis.
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http://dx.doi.org/10.5114/wo.2021.106697DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506436PMC
June 2021

Prognostic and clinicopathological significance of TMEFF2, SMOC-2, and SOX17 expression in endometrial carcinoma.

Exp Mol Pathol 2021 10 31;122:104670. Epub 2021 Jul 31.

Department of Gynecology and Obstetrics, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background there is a need for novel biomarkers and targeting therapies for predicting Endometrial carcinoma (EC) progression and recurrence. TMEFF2 is a gene that was found to play a role in EMT. SMOC-2 is expressed in embryogenesis and it was identified as a recent stem cell-related gene that has a role in cancer progression. SRY-box 17 (SOX17) is a member of the SRY-related HMG-box (SOX) family of transcription factors. Dysregulation or downregulation of SOX17 expression was found in many cancer tissues.

Aim: In the present study, we aimed to assess the tissue protein expressions of TMEFF2, SMOC-2, and SOX17 in EC using immunohistochemistry to evaluate their clinicopathological values and prognostic roles in EC patients.

Patients And Methods: This is prospective cohort study included 120 patients with EC. Sections from 120 paraffin blocks were retrieved and stained with TMEFF2, SMOC-2, and SOX17 using immunohistochemistry, the expression of markers in all tissue samples was assessed, analyzed and correlation of pathological parameters with the levels of expression was done. All patients were followed up till death or till the last known alive data for about 50 months (range from 25 to 60).

Results: TMEFF2, SMOC-2 expression was correlated with the presence of lymph node metastases (p = 0.023), distant metastasis (p = 0.039) recurrence of the tumor after successful therapy, overall survival, and disease-free survival (p < 0.001). SOX17 positive expression was positively correlated with low grade (p = 0.019), absence of lymph node metastasis (p = 0.001), absence of distant metastasis (p = 0.013), low stage (p = 0.03), and its negative expression was positively correlated with recurrence of the tumor after successful therapy, overall survival and disease-free survival (p = 0.001). In conclusion, we demonstrated that both TMEFF2 and SMOC-2 were highly expressed in EC and were associated with a shortened survival rate, dismal outcome, and poor prognosis in EC patients. While SOX17 expression was related to a favorable outcome and its down-regulation was associated with dismal EC patient's survival.
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http://dx.doi.org/10.1016/j.yexmp.2021.104670DOI Listing
October 2021

Choosing the Appropriate Individualized Adjuvant Chemotherapy in Stage III Colon Cancer Patients Under and Over 70 Years.

J Gastrointest Cancer 2021 Jul 20. Epub 2021 Jul 20.

Clinical Oncology & Nuclear Medicine Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background: Colon cancer is one of the leading causes of cancer-related deaths worldwide. The increased incidence of comorbid diseases in elderly patients above 70 leads to the need of less aggressive strategies to be used in the adjuvant setting of stage III colon cancer.

Method: Our prospective cohort study was performed in the period from April 2017 to March 2020. Seventy-five patients with newly diagnosed stage III colon cancer received adjuvant chemotherapy after surgery. Patients who either received adjuvant chemotherapy less than 3 months due to intolerability or toxicity from medications or who have more than one type of cancers or metastatic disease from the start were excluded from the study. Patients' clinicopathological characteristics in relation to oxaliplatin- and non-oxaliplatin-based chemotherapeutic regimens were analyzed with survival assessment.

Results: In our study, patients above 70 had better overall survival (OS) in the non-oxaliplatin chemotherapy group (p-value = 0.032) in contrast to OS in patients under 70 which was better in the oxaliplatin group (p-value < 0.001). By comparing the OS between the two age groups, the OS was better in patients < 70 years (p-value = 0.001). Additionally, we found that the DFS in patients above 70 was better in oxaliplatin-based regimens than in the non-oxaliplatin group (p-value = 0.011) with better survival rates (81.8% vs 15.7%), and markedly high DFS in patients under 70 for oxaliplatin based regimens (p-value < 0.001), with survival rates (31.1% vs 0%). By comparing the DFS between the two age groups, the DFS was better in patients < 70 years (p-value < 0.001). The disease recurrence was in favor of the non-oxaliplatin group with significant p-value = 0.003, while mortality occurred more in the oxaliplatin group (p-value < 0.001).

Conclusions: The appropriate selection of a personalized strategy for treatment of stage III colon cancer plays an important role in the outcome of the disease. Our findings supported the use of oxaliplatin-based chemotherapy as a standard treatment option in the adjuvant management of stage III colon cancer patients in all age groups. The benefit of non-oxaliplatin-based chemotherapy was limited to patients above 70 which might be an effective option for elderly patients.
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http://dx.doi.org/10.1007/s12029-021-00666-2DOI Listing
July 2021

The Diagnostic and Prognostic Roles of Combined Expression of Novel Biomarkers in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: An Immunohistochemical Study.

Iran J Pathol 2021 21;16(2):162-173. Epub 2020 Dec 21.

Histology and Cell Biology Department, Faculty of Medicine, Tanta University, Tanta, Egyp t.

Background & Objective: Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry.

Methods: The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values.

Results: SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC ( 0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (=0.038 and =0.019, respectively).

Conclusion: The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.
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http://dx.doi.org/10.30699/IJP.2020.130944.2452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085294PMC
December 2020

Evaluating the value of Amphiregulin, Phosphatase and Tensin Homologue (PTEN) and P21 Expression for Anti-EGFR Treatment in Metastatic Colorectal Carcinoma.

Asian Pac J Cancer Prev 2021 Apr 1;22(4):1025-1034. Epub 2021 Apr 1.

Department of Pathology, Faculty of Medicine, Zagazig University, Egypt.

Background: Despite the significant progress in target therapy for the treatment of metastatic colorectal carcinoma (mCRC), the overall survival isn't satisfactory.

Methods: We assessed the expression of Amphiregulin, PTEN, and P21 in sections from 23 paraffin blocks prepared from 23 patients with left-sided mCRC using immunohistochemistry (IHC). The relationship between their level of expressions, clinicopathological parameters, response to anti-EGFR, and prognosis were analyzed.

Results: High Amphiregulin, PTEN and low P21 expression levels were associated with low tumor grade (p= 0.038 and 0.025 respectively), better response to anti-EGFR treatment (p <0.001), and favorable outcome {progression-free survival (PFS) and overall survival (OS)} (p <0.05). There was a direct relation between Amphiregulin and PTEN expressions (phi coefficient=+0.840), while there was an inverse relation between P21expression and both Amphiregulin (phi coefficient= -0.840) and PTEN expressions (phi coefficient = -1.000), which was statistically significant (P <0.001).

Conclusion: High Amphiregulin and PTEN expression levels and low P21 expression levels were associated with better response to anti-EGFR therapy and improved survival outcome. They might be considered predictive markers of response to anti-EGFR therapy in mCRC.

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http://dx.doi.org/10.31557/APJCP.2021.22.4.1025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325139PMC
April 2021

The validity, reliability, and reviewer acceptance of VI-RADS in assessing muscle invasion by bladder cancer: a multicenter prospective study.

Eur Radiol 2021 Sep 19;31(9):6949-6961. Epub 2021 Feb 19.

Department of Radio-diagnosis, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.

Objective: To assess diagnostic validity and reliability of VI-RADS in predicting muscle invasion by bladder cancer (BCa) and evaluate reviewer acceptance of VI-RADS for clinical routine.

Methods: A prospective multicenter study enrolled 331 patients with suspected/untreated BCa who underwent preoperative multiparametric MRI examination (mp-MRI) of the urinary bladder. Four experienced radiologists independently evaluated all mp-MRI using VI-RADS. The diagnostic validity of VI-RADS for predicting muscle invasion by BCa was calculated using histopathology of the first transurethral resection bladder tumor (TURBT) and second TURBT as the reference standards. The kappa statistics (κ) were applied to assess the interreader agreement (IRA). Reviewer acceptance was evaluated with questionnaires.

Results: The risk of muscle invasion in VI-RADS 2, 3, 4, and 5 after the first and second TURBT was 21.8%, 45.8%, 69.6%, and 96.4% and 24.4%, 58.3%, 87%, and 99.2%, respectively. The overall diagnostic validity of VI-RADS was high. The optimal cut-off value for predicting muscle invasion after first TURBT was > VI-RADS 3 (sensitivity = 84.1% and specificity = 92.3%), and after second TURBT was > VI-RADS 2 (sensitivity = 89.9% and specificity = 90.1%). VI-RADS categorization showed a very good IRA (κ = 0.93). Reviewers fully agreed with the statement, "The application of structured reporting of bladder tumor should be encouraged" (score = 20).

Conclusions: VI-RADS showed high diagnostic validity and reliability for predicting muscle invasion by BCa, especially VI-RADS 4 and 5. However, VI-RADS 2 and 3 require further modifications to enhance their diagnostic validity. VI-RADS is highly encouraged to be used in daily practice.

Key Points: • VI-RADS showed high diagnostic validity and reliability in predicting BCa muscle invasion, especially VI-RADS 4 and 5. • In VI-RADS 2 and 3, we observed a notable percentage of BCa with muscle invasion and this would require further modifications to enhance the diagnostic validity for these scores. • Overall VI-RADS is well-accepted by radiologists who recommend it for daily practice.
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http://dx.doi.org/10.1007/s00330-021-07765-5DOI Listing
September 2021

Clinico-pathological and prognostic implications of Srx, Nrf2, and PROX1 expression in gastric cancer and adjacent non-neoplastic mucosa - an immunohistochemical study.

Contemp Oncol (Pozn) 2020 4;24(4):229-240. Epub 2021 Jan 4.

General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: Sulfiredoxin (Srx), which is an endogenous antioxidant substance which could, regulate the signaling pathways of reactive oxygen species. Nuclear factor erythroid 2-related factor 2 (Nrf2) is Cap-N-collar (CNC) transcription factors family member that have essential roles in regulation of antioxidant response. The transcription factor PROX1 is a transcription factor and a key regulatory protein in cancer development.

Aim Of The Study: To analyze levels of tissue expression of Srx, Nrf2, and PROX1 in gastric cancer and adjacent non-neoplastic gastric mucosa to clarify the relationship between their expression levels, clinical, pathological parameters and patients' outcome. The results might lead to discovering novel targeted therapies to gastric cancers.

Material And Methods: We included 70 paraffin-embedded samples: 50 specimens from gastric carcinomas and 20 specimens from adjacent non-neoplastic gastric mucosa. All samples are stained with Srx, Nrf2, and PROX1 using immunohistochemistry, correlated their expression with clinicopathological and prognostic parameters of patients.

Results: High levels of Srx and Nrf2 expression were positively associated with higher cancer grade ( = 0.006, 0.031 respectively), advanced stage ( < 0.001, 0.02 respectively), higher incidence of distant metastases ( = 0.029, 0.03 respectively) and dismal outcome ( < 0.001). High levels of PROX1 expression were associated with lower cancer grade ( = 0.005), absence of lymph nodes metastases ( = 0.023), early stage ( = 0.003), absence of relapse ( = 0.004), and favorable outcome ( < 0.001).

Conclusions: Srx and Nrf2 expression increase gastric cancer invasiveness, suggesting their utility as poor prognostic markers, but PROX1 serves as a favorable prognostic marker of gastric cancer patients.
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http://dx.doi.org/10.5114/wo.2020.102671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836280PMC
January 2021

Prognostic and clinic-pathological significances of HOXB8, ILK and FAT4 expression in colorectal cancer.

Contemp Oncol (Pozn) 2020 30;24(3):183-192. Epub 2020 Oct 30.

Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: HOXB8 is a protein that was found to promote cancer proliferation and invasion. ILK is a protein kinase which has a role in carcinogenesis. FAT4 is a tumor homologue that has a role in EMT and autophagy regulation.

Aim Of The Study: To identify expression of Human HOXB8, Integrin-linked kinase (ILK1) and FAT homolog 4 (FAT4) in colorectal cancer (CRC) correlating their expression with pathological, prognostic and clinical parameters of CRC.

Material And Methods: We assessed the expression of HOXB8, ILK and FAT4 in fifty CRC patients and ten samples from nearby non-neoplastic colonic mucosa using immunohistochemistry.

Results: The expression of HOXB8 and ILK in CRC was positively associated with high tumor grade, advanced tumor stage, lymph node involvement ( < 0.001), occurrence of distant metastases ( = 0.003 and 0.024 respectively), higher incidence of tumor recurrence ( = 0.03, < 0.001 respectively), worse survival rates ( = 0.038 and 0.003 respectively). The expression of FAT4 in CRC was correlated with lower grade, early stage of the tumor, absence of lymph node involvement ( < 0.001) and lack of distant metastases ( = 0.011). High FAT4 expression was associated with absence of tumor recurrence ( < 0.001) and favorable survival rates ( < 0.001 and 0.003).

Conclusions: High immunohistochemical expression of HOXB8 and ILK in addition to low immunohistochemical expression of FAT4 was associated with unfavorable prognostic and pathological parameters of CRC.
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http://dx.doi.org/10.5114/wo.2020.100281DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670183PMC
October 2020

TFAP2B, AP-1 and JAZF1 Expression in Tissues of Papillary Thyroid Carcinoma Patients; Clinical, Pathological and Prognostic Values.

Asian Pac J Cancer Prev 2020 Aug 1;21(8):2415-2421. Epub 2020 Aug 1.

Department of Biology, College of Science, University of Hafr Al Batin, Hafr Al Batin, Saudi Arabia.

Objective: Transcription factor activating protein 2 B (TFAP2 B) is a transcription factor that regulates many steps of embryogenesis, cell growth, apoptosis and recently oncogenesis and cancer progression. AP-1 is a transcription factor that is a downstream molecule of the MAPK signaling pathway. Juxtaposed with zinc finger gene 1 (JAZF1) is a recently detected transforming growth factor which has a role in carcinogenesis. Hence the present study aimed to assess those markers expression in tissues from patients with such cancer correlation their expression with clinic-pathological findings of the tumor and prognostic and follow-up findings of patients.

Methods: We have collected tissue samples from papillary thyroid cancer patients and adjacent non-neoplastic tissues from 80 patients. We assessed the expression of TFAP2B, AP-1 and JAZF1 using immunohistochemistry.

Results: Expression of TFAP2B was positively associated with lymph nodes metastases (p=0.003), distant metastases (p=0.002), recurrence of the tumor (p=0.002), unfavourable disease-free survival rate (p=0.003). AP-1 expression is positively associated with advanced stage (p=0.002), presence of extra-thyroid invasion (p=0.005), recurrence of the tumor (p=0.005), unfavorable disease-free survival rate (p=0.01). JAZF1 expression is negatively associated with huge tumor size (0.023), vascular invasion (p=0.007) and unfavorable overall survival rate (p=.030).

Conclusion: High expression levels of TFAP2B and AP-1 and low expression levels of JAZF1 were associated with unfavourable pathological, prognostic parameters and dismal patient's outcome.
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http://dx.doi.org/10.31557/APJCP.2020.21.8.2415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771927PMC
August 2020

Comparison of O-RADS, GI-RADS, and IOTA simple rules regarding malignancy rate, validity, and reliability for diagnosis of adnexal masses.

Eur Radiol 2021 Feb 18;31(2):674-684. Epub 2020 Aug 18.

Department of Radio-diagnosis, Benha University, Benha, Egypt.

Objective: The American College of Radiology (ACR) recently published the ovarian-adnexal reporting and data system (O-RADS) to provide guidelines to physicians who interpret ultrasound (US) examinations of adnexal masses (AM). This study aimed to compare the O-RADS with two other well-established US classification systems for diagnosis of AM.

Methods: This retrospective multicenter study between May 2016 and December 2019 assessed consecutive women with AM detected by the US. Five experienced consultant radiologists independently categorized each AM according to O-RADS, gynecologic imaging reporting and data system (GI-RADS), and international ovarian tumor analysis (IOTA) simple rules. Pathology and adequate follow-up were used as reference standards for calculating the validity of three US classification systems for diagnosis of AM. Kappa statistics were used to assess the inter-reviewer agreement (IRA).

Results: A total of 609 women (mean age, 48 ± 13.7 years; range, 18-72 years) with 647 AM were included. Of the 647 AM, 178 were malignant and 469 were benign. Malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS. O-RADS had significantly higher sensitivity for malignancy than GI-RAD and IOTA (p = 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (p > 0.05). O-RADS, GI-RADS, and IOTA showed similar overall IRA (κ = 0.77, 0.69, and 0.63, respectively) with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA.

Conclusions: O-RADS compares favorably with GI-RADS and IOTA. O-RADS had higher sensitivity than GI-RADS and IOTA simple rules with relatively similar specificity and reliability.

Key Points: • The malignancy rates were comparable to recommended rates by previous literature in O-RADS and IOTA, but higher in GI-RADS. • The O-RADS had significantly higher sensitivity for malignancy than GI-RADS and IOTA (96.8% vs 92.7% and 92.1%; p = 0.003 and 0.0007, respectively), but non-significant slightly lower specificity (92.8% vs 93.6% and 93.2%, respectively; p > 0.05). • The O-RADS, GI-RADS, and IOTA showed similar overall inter-reviewer agreement (IRA) (κ = 0.77, 0.69, and 0.63, respectively), with a tendency toward higher IRA with O-RADS than with GI-RADS and IOTA.
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http://dx.doi.org/10.1007/s00330-020-07143-7DOI Listing
February 2021

Prognostic Significances of NEDD-9 and FOXL-1 Expression in Intestinal Type Gastric Carcinoma: an Immunohistochemical Study.

J Gastrointest Cancer 2021 Jun;52(2):728-737

Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background: Gastric cancer (GC) is mostly diagnosed at advanced stage, so prognosis is poor. Therefore, it is necessary to understand the molecular mechanism of GC development to design new targeted treatment to improve the prognosis of gastric cancer patients.

Aim Of The Work: To assess the prognostic value of NEDD-9 and FOXL-1 expression in intestinal type gastric cancer patients, as well as their relationship to clinicopathologic features of the disease and patients outcome.

Patients And Methods: This is a retrospective study; we included 50 sections from formalin-fixed, paraffin-embedded tissue samples which included intestinal type GC and adjacent non-neoplastic gastric mucosa in the same block that were subjected to immunohistochemistry with anti-NEDD-9 and anti-FOXL-1 antibody. Patients were retrospectively followed up for about 5 years for assessment of tumor progression and survival in relation to marker expression.

Results: High NEDD-9 and low FOXL-1 expression were found in intestinal type GC more than adjacent non-neoplastic mucosa (p < 0.001). NEDD-9 high expression and FOXL-1 low expression were associated with presence of helicobacter pylori gastritis (p = 0.010, 0.049), high grade (p = 0.007, 0.004), high stage (p < 0.001), presence of distant metastases (p = 0.029, 0.021), poor DFS (p = 0.003), and OS rates (< 0.001).

Conclusion: NEDD-9 overexpression and FOXL-1 deficiency in intestinal type GC can help in prediction of tumor prognosis and it can guide the selection of patients for future therapies in gastric carcinoma.
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http://dx.doi.org/10.1007/s12029-020-00471-3DOI Listing
June 2021

Prognostic and clinicopathological values of tissue expression of MFAP5 and ITM2A in triple-negative breast cancer: an immunohistochemical study.

Contemp Oncol (Pozn) 2020 3;24(2):87-95. Epub 2020 Jul 3.

Department of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Introduction: Triple-negative breast cancer (TNBC) is a markedly aggressive molecular subtype of breast cancer; there is an urgent need to clarify the molecular mechanisms underlying the progression and metastases of BLBC, in order to find a novel targeted therapy. Microfibrillar-associated protein 5 (MFAP5) plays an essential role in the regulation of cell behaviour and survival. Integral membrane protein 2A (ITM2A) is a type II transmembrane protein, which is a member of a family of autophagy related proteins.The aim of this study was to assess the expression of MFAP5 and ITM2A proteins in tissues of BLBC using immunohistochemistry, in order to correlate the expression with clinicopathological and prognostic parameters of such aggressive cancer.

Material And Methods: The present study included sections from archived paraffin blocks retrieved from 120 patients with TNBC. We collected cases from three years, i.e. from 2016 to 2019. We assessed expression of MFAP5 and ITM2A using immunohistochemistry.

Results: High expression of MFAP5 and low expression of ITM2A was associated with advanced stage ( = 0.007), higher grade of tumour ( = 0.005 and = 0.004, respectively), the presence of lymph nodes metastases ( < 0.001 and = 0.002, respectively), lower three-year RFS rate ( < 0.001 and = 0.016, respectively), and lower three-year OS rate ( < 0.001).

Conclusions: MFAP5 and ITM2A are novel prognostic biomarkers for breast cancer and might be considered as promising therapeutic targets for patients with breast cancer, particularly TNBC molecular subtype, in the future.
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http://dx.doi.org/10.5114/wo.2020.97520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7403766PMC
July 2020

Validity and Reproducibility of the ADNEX MR Scoring System in the Diagnosis of Sonographically Indeterminate Adnexal Masses.

J Magn Reson Imaging 2021 01 26;53(1):292-304. Epub 2020 Jul 26.

Department of Radio-Diagnosis, Faculty of Human Medicine, Zagazig University, Zagazig, Egypt.

Background: The diagnosis of sonographically indeterminate adnexal masses (AM) signifies a major challenge in clinical practice. Early detection and characterization have increased the need for accurate imaging evaluation before treatment.

Purpose: To assess the validity and reproducibility of the ADNEX MR Scoring system in the diagnosis of sonographically indeterminate AM.

Study Type: A prospective multicenter study.

Population: In all, 531 women (mean age, 44 ± 11.2 years; range, 21-79 years) with 572 sonographically indeterminate AM.

Field Strength/sequence: 1.5T/precontrast T -weighted imaging (WI) fast spin echo (FSE) (in-phase and out-of-phase, with and without fat suppression); T -WI FSE; diffusion-WI single-shot echo planner with b-values of 0 and 1000 s/mm ; and dynamic contrast-enhanced perfusion T -WI liver acquisition with volume acceleration (LAVA).

Assessment: All MRI examinations were evaluated by three radiologists, and the AM were categorized into five scores based on the ADNEX MR Scoring system. Score 1: no AM; 2: benign AM; 3: probably benign AM; 4: indeterminate AM; 5: probably malignant AM. Histopathology and imaging follow-up were used as the standard references for evaluating the validity of the ADNEX MR Scoring system for detecting ovarian malignancy.

Statistical Tests: Four-fold table test, kappa statistics (κ), and receiver operating characteristic (ROC) curve.

Results: In all, 136 (23.8%) AM were malignant, and 436 (76.2%) were benign. Of the 350 AM classified as score 2, one (0.3%) was malignant; of the 62 AM classified as score 3, six (9.7%) were malignant; of the 73 AM classified as score 4, 43 (58.9%) were malignant; and of the 87 AM categorized as score 5, 86 (98.9%) were malignant. The best cutoff value for predicting malignant AM was score >3 with sensitivity and specificity of 92.9% and 94.9%, respectively. The interreader agreement of the ADNEX MR Scoring was very good (κ = 0.861).

Data Conclusion: The current study supports the high validity and reproducibility of the ADNEX MR Scoring system for the diagnosis of sonographically indeterminate AM.

Level Of Evidence: 1 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27285DOI Listing
January 2021

The validity of grayscale and color Doppler ultrasound in assessment of scrotal swellings: a retrospective study in a large case series.

Acta Radiol 2021 Feb 26;62(2):266-275. Epub 2020 Apr 26.

Department of Radio-diagnosis, Faculty of Human Medicine, Benha University, Benha, Egypt.

Background: Scrotal swellings have a non-specific clinical picture, so their clinical diagnosis is challenging. Scrotal grayscale and color Doppler ultrasound are non-invasive methods used in both adult and childhood groups and act as accurate screening and diagnostic modalities.

Purpose: To evaluate the diagnostic validity of grayscale and color Doppler ultrasound in the assessment of scrotal swelling to reach accurate diagnosis.

Material And Methods: A retrospective study included 181 patients (mean age = 35.5 ± 7.3, age range = 1-71 years) with scrotal swelling. Examinations were performed by an experienced radiologist using grayscale and color Doppler ultrasound. The diagnostic validity of grayscale and color Doppler ultrasound for diagnosing scrotal swelling were estimated using surgical findings, histopathological results, and imaging and clinical follow-up as reference standards.

Results: Overall, 202 scrotal swellings were detected. The final diagnoses were 13 (6.4%) malignant and 189 (93.6%) benign alterations. Varicocele was the most common scrotal swelling (26%), followed by hydrocele (23.8%). Matched to the reference standards, grayscale and color Doppler ultrasound represented a sensitivity of 84.6% (95% confidence interval [CI] = 54.6-98.1), a specificity of 76.2% (95% CI = 69.5-82.1), a positive predictive value of 19.6% (95% CI = 10.2-32.4), and a negative predictive value of 98.6% (95% CI = 95.1-99.8) for diagnosing scrotal tumors.

Conclusion: Scrotal grayscale and color Doppler ultrasound provide high diagnostic validity for assessment of scrotal swellings.
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http://dx.doi.org/10.1177/0284185120916836DOI Listing
February 2021

Prognostic Significance of VEGF and HIF-1 α in Hepatocellular Carcinoma Patients Receiving Sorafenib Versus Metformin Sorafenib Combination.

J Gastrointest Cancer 2021 Mar;52(1):269-279

Medical Oncology Department, Faculty of Medicine, Zagazig University, Zagazig, 44519, Egypt.

Background: Hepatocellular carcinoma (HCC) is a major health problem. HCC burden has been increasing in Egypt in the past 10 years. Most HCC cases are diagnosed at an advanced stage with limited treatment options. Sorafenib is the standard therapy for advanced HCC, but the effectiveness is not satisfied. Metformin may decrease the risk of HCC development in diabetic patients, reduces tumor invasion, and augments sensitivity to sorafenib; however, safety and efficacy of combined treatment are still unclear. As HCC is characterized by high vascularity, and vascular endothelial growth factor (VEGF) plays an important role in vascularization, many studies questioned if VEGF and HIF-1 α could offer information about HCC response to sorafenib. We conducted this study to assess the benefits from adding metformin to HCC treatment, and appraise the role of VEGF and HIF-1 α in HCC prognosis.

Method: This was a prospective, randomized study in which 80 advanced measurable patients consecutively treated with sorafenib plus metformin (arm A) or sorafenib alone (arm B), prognostic value of plasma, and tissue levels of VEGF and HIF-1 α were evaluated.

Results: We enrolled 61 men and 19 women with a median age of 60 years (range 49-68 years). Fifty-seven patients had Child-Pugh A while 23 had early B, the most common etiology of liver disease was hepatitis C (86%). Sixty percent of patients were diabetic. No significant difference was detected between arm A and arm B regarding response to treatment (p = 0.5), time to disease progression (p = 0.3), or overall survival (p = 0.6). Low VEGF and HIF-1 α plasma levels were significantly associated with better treatment response (p < 0.001 for both), and higher OS (p < 0.001). Patients with high expressions of VEGF and HIF in HCC tissue had significantly poor treatment outcome (p < 0.001, p = 0.03, respectively), and poor OS (p < 0.001, p < 0.001, respectively).

Conclusions: No superior efficacy of adding metformin to sorafenib in HCC treatment. VEGF and HIF-1 α had promising prognostic value in HCC.
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http://dx.doi.org/10.1007/s12029-020-00389-wDOI Listing
March 2021

The Diagnostic Value of Arginase-1, FTCD, and MOC-31 Expression in Early Detection of Hepatocellular Carcinoma (HCC) and in Differentiation Between HCC and Metastatic Adenocarcinoma to the Liver.

J Gastrointest Cancer 2020 Mar;51(1):88-101

Department of Medical Oncology, Faculty of Medicine, Zagazig University Zagazig, Zagazig, Egypt.

Background: Early detection of small HCC and differentiation between HCC from AC metastatic to the liver is very essential for surgical pathologists, due to different treatment modalities. Immunohistochemistry plays a very important role in such conditions. In our study, we aimed to identify the diagnostic benefits of Arginase-1, FTCD& MOC-31 in the early detection of HCC in normal or cirrhotic liver, differentiation between HCC and metastatic ACs to the liver, and for early detection of small micro-metastases from ACs to liver.

Materials And Methods: We included 20 samples from liver cirrhosis, 10 samples from normal liver tissue, 30 samples from primary HCCs in the liver, and 30 samples from metastatic ACs to the liver. We have evaluated Arginase-1, FTCD, and MOC-31 expression using immunohistochemistry.

Results: The sensitivity of Arginase-1 expression in differentiation between HCC and metastatic carcinoma was 93.3% and the specificity was 93.3%. The sensitivity of FTCD expression in differentiation between HCC and normal or cirrhotic liver and early detection of well-differentiated HCC was 90% and the specificity was 86.7%. The sensitivity of MOC-31 expression in differentiation between HCC and metastatic carcinoma was 90% and the specificity was 90%. The sensitivity of combination of panel of Arginase 1 + FTCD + MOC 31 expression in differentiation between HCC, metastatic carcinoma, and normal and cirrhotic liver was 93.3% and the specificity was 93.3%.

Conclusions: The combination of Arginase 1 + FTCD + MOC 31 expression was helpful in diagnosing most cases of HCC and metastatic carcinoma with high sensitivity and specificity.
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http://dx.doi.org/10.1007/s12029-019-00211-2DOI Listing
March 2020

The Expression of FOXE-1 and STIP-1 in Papillary Thyroid Carcinoma and Their Relationship with Patient Prognosis.

Iran J Pathol 2018 17;13(2):256-271. Epub 2018 Jul 17.

Dept. of General Surgery, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background & Objective: Most patients with papillary carcinoma of the thyroid gland (PTC) havefavorable outcome,but sinceit has severe capability to invade the nearby tissues, there isa great risk of regional and distal lymph-nodes (LNs) metastases related to poor prognostic parameters, early recurrences, and distant metastasis that lead to bad patient outcome. Discovering other prognostic biomarkers for this cancer helps to detect early recurrences, invasion, expecting patient outcome, and possible use as therapeutic-targets for it. The , with the alternative name of , is one of thetranscription factors familiesthat is huge and containsa special fork-head-domain. It has a significant role in the differentiation and maturation of thyroid-follicular cells. Stress-induced phosphor-protein-1 (STIP-1), withthe alternative name ofheat-shock-protein-(HSP)organizing protein,is a 62.6-kD protein, with three parts of tetra-trico-peptide repeats (TPR), and is capable of interaction with heat-shock proteins forming structures that haveplethora of roles in variable cellular processes;e.g., cell cycles regulations, transcriptions, and RNA splicing.The current study aimed at exploring the relationship between and expressions, the clinicopathological parameters, prognosis, and survival of patients with PTC.

Methods: The current studyexplored and expressions by the immunohistochemical methods in 36 paraffin blocks retrieved from 36 patients of PTC, analyzed the relationships between their levels of expression,clinicopathological parameters, prognosis, and survival of patients.

Results: The high expression levels forboth and in PTC were associated with larger size of the tumor, extra-thyroidal extension, vessels invasion, LNs spread ( <0.001), presence of distant metastases (P values = 0.005 and 0.012, respectively) and higher stages of the cancer (P values =0.012 and 0.042, respectively).The over-expression was associated with shortened distant metastases free survival (DMFS) and shortened five-year overall survival rates (OS) ( <0.001).

Conclusion: Patients withadvanced PTC andunfavorable prognosis had high levels of both and expressions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6339506PMC
July 2018

Prognostic and Clinic-Pathological Significances of SCF and COX-2 Expression in Inflammatory and Malignant Prostatic Lesions.

Pathol Oncol Res 2019 Apr 6;25(2):611-624. Epub 2018 Nov 6.

Urology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

The initiation of prostatic malignancy has been linked to chronic inflammation. Stem cell factor (SCF) is an inflammatory cytokine that is specific to the c-KIT receptor which is type III receptor tyrosine kinase (RTK). Cyclooxygenases (COXs) are the main enzymes which are responsible for prostaglandins production from arachidonic acid. COX2 is an enzyme which is produced under different pathological conditions. The aim of our study; is to investigate the clinicopathological and the prognostic significance of SCF and COX-2 expression in prostatic adenocarcinoma (PC), chronic prostatitis and nodular prostatic hyperplasia (NPH) in a trial to clarify the role of inflammation as a risk factor for prostatic carcinogenesis and cancer progression. SCF and COX-2 tissue protein expression were evaluated in 50 cases of PC, 20 cases of chronic prostatitis and 10 cases of NPH using immunohistochemistry, patients were followed up for 5 years. The relationship between their levels of expressions, clinicopathological, and prognostic criteria were studied. SCF expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.010), higher Gleason score (p = 0.011). COX-2 expression in PC was positively correlated with advanced patient age (p = <0.001), high level of PSA (p = 0.016), advanced D'Amico risk group (p = 0.038). High levels of expression of both SCF& COX-2 are associated with higher incidence of tumor relapse, worse disease overall survival and free survival (p < 0.001). SCF and COX-2 are associated with PC progression and associated with poor prognosis in PC patients.
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http://dx.doi.org/10.1007/s12253-018-0534-1DOI Listing
April 2019

Primary diffuse large B-cell non-Hodgkin's lymphoma of the breast-A case report and review of the literature.

Radiol Case Rep 2019 Jan 4;14(1):22-27. Epub 2018 Oct 4.

Department of Radiology, Faculty of Medicine, Zagazig University, Egypt.

Primary breast lymphoma (PBL) is considered a rare clinical entity forming about 0.4%-0.5% of all breast tumors. In this report we have presented a case of PBL in a 56-year-old female complaining of a mass in the upper medial quadrant of the breast. PBL suspicion of our case was made by breast radiology and the sure diagnosis was reached by the immunohistochemistry results; CD (cluster of differentiation) 20: was diffusely positive; Pan-CK (pan-cytokeratin): was diffusely negative in tumor cells. Hence, the case was finally diagnosed as a primary breast a primary breast diffuse large B-cell non-Hodgkin's lymphoma of lymphoma. The management and outcome of PBL and carcinoma are totally different. Accurate diagnosis of PBL by true cut needle biopsy and immunocytochemistry is important to avoid unnecessary mastectomies.
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http://dx.doi.org/10.1016/j.radcr.2018.09.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172487PMC
January 2019

SPOP, ZEB-1 and E-cadherin expression in clear cell renal cell carcinoma (cc-RCC): Clinicopathological and prognostic significance.

Pathophysiology 2018 Dec 18;25(4):335-345. Epub 2018 May 18.

Department of Internal Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt. Electronic address:

Background: Clear cell renal cell carcinoma (cc-RCC), is a serious cancer regarding; its fatality, liability for metastases and chemoresistance, so identification of recent therapeutic targets to improve the patients prognosis is needed. SPOP is a BTB/POZ domain containing speckle-type POZ protein, has been identified as an E3 ubiquitin ligase component. ZEB1 is an essential epithelial mesenchymal transition (EMT) activator; E-cadherin is a cell adhesion protein that had been detected in normal epithelial cells membrane.

Aim: Was to assess the tissue protein markers SPOP, ZEB1 & E-cadherin expressions in benign areas of neoplastic kidney specimens and in cc-RCC patients, then correlating their expression levels with patients clinicopathological and prognostic data.

Methods: We evaluated SPOP, ZEB-1 & E-cadherin expression using immunohistochemistry in samples from 50 cc-RCC and 20 benign areas of neoplastic kidney specimens, then we followed our patients for 5 years and finally we have analyzed correlations between the levels of markers expressions with patients clinicopathological and prognostic criteria in cc-RCC.

Results: Positive expression of SPOP & ZEB1 in addition to negative E- cadherin expression was detected in cc-RCC more than benign areas of neoplastic kidney specimens (p = 0.004 and p < 0.001 respectively). In cc-RCC Positive expression of SPOP, ZEB1 and negative E- cadherin expression was associated with higher grade (p = 0.006, 0.007 & <0.001 respectively), advanced AJCC stage (p = 0.013, 0.023 & <0.001 respectively), presence of L.N metastases (p = 0.002 = 0.010 and <0.001 respectively), distant metastases (p = 0.001, 0.003 & 0.035 respectively), poor PFS and OS rates (p < 0.001 and p = 0.013 respectively).

Conclusion: Positive expression of SPOP& ZEB1 in addition to negative E- cadherin are associated with poor prognosis in cc-RCC patients.
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http://dx.doi.org/10.1016/j.pathophys.2018.05.004DOI Listing
December 2018

The role of neural precursor cell-expressed developmentally down-regulated protein 9 in predicting bacillus Calmette-Guerin response in nonmuscle invasive bladder cancer.

Urol Oncol 2018 May 5;36(5):242.e9-242.e14. Epub 2018 Mar 5.

Urology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Objective: To report the sensitivity and specificity of neural precursor cell-expressed developmentally down-regulated protein 9 (NEDD9) protein high expression in predicting BCG response and its effect on recurrence or progression free survivals.

Patients And Methods: Between May 2014 and April 2017, a prospective cohort study was conducted on 105 patients with intermediate or high-risk nonmuscle invasive bladder cancer. Immunohistochemical staining with mouse monoclonal anti-NEDD9 antibody was done. Examination of the slides was done to detect NEDD9 cytoplasmic expression. Intravesical induction bacillus Calmette-Guerin (BCG) instillation therapy was started for all patients 2 to 4 weeks after endoscopy with once weekly instillation for 6 weeks. Intravesical maintenance BCG instillation was then continued every 3 months for at least 1 year. Follow up with cystoscopy every 3 months for 2 years and every 6 months after that.

Results: The mean age ± SD of the patients was 57 ± 4.5 years. The median follow-up period was 25 (12-36) months. NEDD9 protein was highly expressed in 61 (58.1%) patients, whereas low expression was in 44 (41.9%) patients. Sensitivity and specificity of NEDD9 high expression in predicting recurrence were 83.6% and 64.2%, respectively. Its sensitivity and specificity in predicting progression to muscle invasion or distant metastases were 91.3% and 51.2%, respectively. Its sensitivity and specificity in predicting complete response to BCG therapy were 84.1% and 80.9%. Kaplan-Meier test showed highly significant difference (P<0.0001) in survival without recurrence or progression between patients showing high expression and those showing low expression.

Conclusion: NEDD9 protein tissue marker could be used as a predictive marker for BCG response in nonmuscle invasive bladder cancer with reasonable sensitivity and specificity.
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http://dx.doi.org/10.1016/j.urolonc.2018.02.002DOI Listing
May 2018

Thioredoxin-Interact ing-Pro t e in [TXNIP] and Transglutaminase 2 [TGM2] Expression in Meningiomas of Different Grades and the Role of Their Expression in Meningioma Recurrence and Prognosis

Asian Pac J Cancer Prev 2017 08 27;18(8):2299-2308. Epub 2017 Aug 27.

Pathology Department, Faculty of Medicine, Zagazig University, Egypt. Email:

Background: Meningiomas are common central nervous system (CNS) tumors that account for thirty percent of primary intracranial tumors.. The accuracy of predicting meningioma recurrence and progression is not enough. So, there is a real need for discovering recent factors for identification of the relapse risk, progression rates, which patients will need aggressive treatment and predicting and improving patients’ survival. Thioredoxin-interacting-protein [TXNIP] is an alpha-arrestin-protein family member that is mapped on chromosome 1-q21–22 and is found to participate in cellular redox reactions regulations and control. Transglutaminase 2 (TGM2) is a transglutaminase enzyme family member that is found in many human cells, it may act as an enzyme, a structural protein and also has multiple roles in many cellular activities. Aim of our study: It was to explore the expression of TXNIP, TGM2 and Ki-67 using immunohistochemistry in different pathological grades of meningiomas, and to investigate the relevance between their expressions, clinicopathological criteria, disease recurrence and prognosis of meningioma patients. Methods: we included 50 cases of meningioma of different pathological grades; all patients were managed according to their grade by surgery alone, with radiotherapy or combined modalities. Sections from paraffin blocks prepared from samples of all patients stained by TXNIP, TGM2 and Ki-67 using immunohistochemistry. Results: high expression of TXNIP in 28 out of 50 (56%) cases of meningioma of different pathological grades and was positively correlated with meningioma lower grade, low KI labeling index (p=0.000), adequacy of resection, negatively correlated with high incidence of recurrence after surgery and it was negatively correlated with meningioma higher pathological grades (p=0.000). We detected high expression of TGM2 in 21 out of 50 (42%) cases of meningioma and it was positively correlated with meningioma higher grade (p= 0.002), high KI labeling index (p=0.000), high incidence of recurrence after surgery, progression to higher pathological grades and was negatively correlated with adequacy of resection of meningioma (p=0.000). Conclusion: There is inverse relation between both [TXNIP and TGM2 expression in meningiomas and the combination of decreased expression of TXNIP and increased expression of TGM2 could predict risk of meningioma recurrence and progression in to higher pathological grades.
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http://dx.doi.org/10.22034/APJCP.2017.18.8.2299DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5697495PMC
August 2017

The Prognostic Role of NEDD9 and P38 Protein Expression Levels in Urinary Bladder Transitional Cell Carcinoma.

J Oncol 2017 17;2017:6095205. Epub 2017 Jan 17.

Department of Urology, Faculty of Medicine, Zagazig University, Sharkia, Egypt.

The most common malignant tumor of the urinary bladder is transitional cell carcinoma (TCC). Neural precursor cell-expressed developmentally downregulated protein 9 (NEDD9) is found to be a cell adhesion mediator. P38 Mitogen-Activated Protein Kinase is a serine/threonine kinases member which can mediate carcinogenesis through intracellular signaling. To assess their prognostic role; NEDD9 and p38 protein were evaluated in sections from 50 paraffin blocks of TCC. The high expressions of NEDD9 and p38 protein were significantly associated with grade, stage, distant metastasis ( < 0.001), number of tumors, lymph node metastasis, and tumor size ( < 0.001, 0.002; 0.018, <0.001; and 0.004, 0.007, respectively). High NEDD9 and p38 detection had a worse 3-year OS ( = 0.041 and <0.001, respectively). By multivariate analysis the NEDD9 and p38 protein expression levels and various clinicopathological criteria including gender, grade, stage of the tumor, and regional lymph node involvement were independent prognostic parameters of TCC of the urinary bladder patients' outcome. NEDD9 and p38 protein expressions were poor prognostic markers of TCC.
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http://dx.doi.org/10.1155/2017/6095205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5282419PMC
January 2017
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