فهرست مطالب

  • Volume:15 Issue: 4, Autumn 2020
  • تاریخ انتشار: 1399/06/22
  • تعداد عناوین: 17
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  • Anahita Nosrati * Pages 259-260

    Coronaviruses are considered to be one of the most significant human and animal pathogens. In late 2019, a new species of coronavirus was recognized as the cause of some pneumonia cases in Wuhan, China. The disease spread rapidly and made an epidemic in China and subsequently in almost all countries in the world. In February 2020, the World Health Organization (WHO) named it as COVID-19 standing for Coronavirus 2019 (1). Due to being a pandemic issue, it is needed to discuss various aspects of this viral disease. Recently, Yan Zhang et al. reported a case of coagulopathy and antiphospholipid antibodies in the patient with severe COVID-19 infection (2). Thus, one of the serious complications of COVID-19 that should be taken into consideration is coagulopathy with possible anti-phospholipid antibodies syndrome in these patients. In this regard, some studies also claimed that COVID-19 could cause venous and arterial thromboembolism because of excessive inflammation, hypoxia, immobility, and diffuse intravascular coagulation (3). Antiphospholipid syndrome is a systemic autoimmune disease with vascular and hematologic complications as venous and arterial thrombosis or pregnancy morbidity (4). It is well known that infectious agents are one of the major stimulators of the antiphospholipid antibodies in vivo (5), thus, COVID-19 can be a possible cause of this phenomenon within its infection period and consequently, positive results of  antiphospholipid antibodies detection are not unexpected.

    Keywords: Coagulation changes, COVID-19, DIC
  • Fereshteh Atabi, Reza Mohammadi * Pages 261-267
    Background & Objective

      Concentration of low-density lipoprotein (LDL) is a known risk factor for cardiovascular disease which is routinely measured or calculated as LDL-C in clinical laboratories. In order to decrease the cost, instead of its measuring, it is recommended to calculate it using multiple formulas that have been introduced up to now. The aim of this study was to assess the results of various formulas and comparison of these results with those of measuring method and to clarify the best formula for the Iranian population.

    Methods

      Concentrations of total cholesterol (TC), triglyceride (TG), cholesterol of high-density lipoprotein (HDL-C) and LDL-C in serums of 471 overnight fasting individuals were measured and also LDL-Cs of these samples were calculated by eleven different formulas according to their TC, TG, and HDL-C concentrations. Subsequently, results of measured and calculated LDL-C were analyzed statistically by paired t-test, correlation coefficient, and Passing-Bablok regression. In addition, for clinical evaluation, the differences between calculated and measured mean results were calculated and compared with an allowable total error.

    Results

      Paired t-test unraveled a significant difference between the results of measured and calculated LDL-C by various formulas. But for some formulas, these differences were not clinically significant. The best clinical and statistical agreement (correlation coefficient) was obtained by the Friedewald equation.

    Conclusion

      By using validated methods which have correct calibration and control system for measuring TC, TG, and HDL-C, we can use the Friedewald formula for calculating LDL-C in serum samples with TG up to 400 mg/dL.

    Keywords: cardiovascular disease, LDL, Friedewald formula, HDL, TG
  • Apurv Ghosh, M Nirupama *, Nandan Padmanabha, Hema Kini Pages 268-273
    Background & Objective

      Cervical cancer is the most common cancer in women worldwide with high mortality, necessitating quicker diagnostic methods. We wish to enhance the existing cervical biopsies of Squamous Intraepithelial Lesions (SIL) using p16 and Ki67 as surrogate markers to assess correlation between its positivity and histological grade of the lesion.

    Methods

      Analysis of p16 and Ki67 expression was done on 31 histopathologically diagnosed cases of SILs. Positive expression of p16 was assessed based on a scoring system and compared with histology and cytology. Ki67 expression was studied and the correlation was observed with degree of dysplasia. Twenty cases of chronic cervicitis was assigned to the control group for comparison.

    Results

      Cases of HSIL showed greater expression of p16 as compared to LSIL. Sensitivity of p16 for HSIL was higher than that for LSIL. The specificity for HSIL and LSIL was 100%. Ki67 expression correlated well with the degree and level of dysplasia with a significant P-value of 0.002.

    Conclusion

      p16 and Ki67 positivity of SILs should point towards further evaluation. The expressions of p16 and Ki67 are useful markers for confirmation of SILs and in predicting HPV infection which can be further confirmed by HPV DNA testing.

    Keywords: Squamous intraepithelial lesion, HSIL, LSIL
  • Mitra Heidarpour, Mehran Taheri, Ali Akhavan, Parvin Goli, Amirhosein Kefayat * Pages 274-281
    Background & Objective

      Human epidermal growth factor receptor 2 (HER-2) exhibits a vast range of expression in esophageal squamous cell carcinoma (ESCC) patients as a biomarker. This paper aimed to investigate HER-2 expression and clinicopathological parameters of esophageal SCC.

    Methods

      HER-2 expression was assessed in 102 ESCC patients by immunohistochemistry. The HER-2 staining intensity , according to the Gastric HER2 Biomarker1.0.0.1 version of the college of American pathologists (CAP) protocol for gastric and gastroesophageal junction cancers, was graded as 0 (no reactivity in any of the cancer cells’ membranes); 1+ (pale or hardly noticeable reactivity in the membrane of cancer cells’ cluster [≥ 5 neoplastic cells] regardless of the positive cancer cells’ percentage); 2+ (weak-to-moderate complete, basolateral, or lateral membranous reactivity regardless of the positive cancer cells’ percentage); and 3+ ( strong complete, basolateral, or lateral reactivity in the membrane of the cancer cell cluster regardless of the positive cancer cells’ percentage).In this regard, 3+ scored samples were considered as positive. If HER-2 expression was scored 2+, an additional fluorescence in situ hybridization (FISH) was performed. Fisher's exact test was employed for investigating the correlation of HER-2 expression status with patients’ clinicopathological characteristics (including age, gender, tumor location, stage, grade, infiltration level, venous invasion, lymphatic invasion, and tumor recurrence). Kaplan-Meier analysis was done for the patients’ survival assessments.

    Results

      Five patients (~5%) were HER-2 positive and no significant association was observed between HER-2 expression and clinicopathological properties. In addition, HER-2 expression status exhibited no significant association with the patients’ overall survival (p =0.9299). 

    Conclusion

      HER-2 is not a suitable prognostic biomarker for Iranian ESCC patients.

    Keywords: HER-2 receptor, Esophageal cancer, Squamous cell carcinoma
  • Shaghayegh Rostami Yasuj, Narges Obeidi *, Gholamreza Khamisipour, Zeynab Gharehdaghi, Zivar Zangeneh Pages 282-291
    Background & Objective

      Acute lymphoblastic leukemia (ALL) is a malignant disease that arises from various mutations in B or T-lymphoid progenitors. MicroRNAs (miRNAs) regulate gene expression by binding to the 3' untranslated region of protein-coding genes. Dysregulation of miRNA expression may result in the development of cancerous phenotypes. Therefore, for the first time in this field, the present study aims to investigate the effect of overexpression of miR-506 in Jurkat (acute T cell leukemia) cell line.

    Methods

      In this study, Jurkat cell lines were cultured in RPMI-1640 medium. Next, miR-506 was transfected with concentrations of 50 and 100 nM with Lipofectamine 2000. The accuracy of the transfection was confirmed by the transfection of siRNA conjugated with FITC. 48 h after transfection, the cells were prepared for other tests (flow cytometry, MTT assay, and RNA extraction). The expression level of miR-506 in the cells was analyzed using the quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). Finally, SPSS 21 software was used for the data analysis.

    Results

      According to our results, the viability of cells in concentrations of 50 and 100 nM was significantly higher than the control group. By overexpression of miR-506, the expressions of pro-apoptotic genes (p53, p21) and anti-apoptotic gene B-cell lymphoma-2 (BCL-2) are decreased and increased, respectively.

    Conclusion

      This study showed that miR-506 may function as an oncogenic miRNA in the T- ALL cell line. In conclusion, overexpression of miR-506 leads to an increase in viable cancer cells.

    Keywords: MicroRNA, miR-506, Jurkat cell, p53 Genes, Acute Lymphoid Leukemia, Apoptosis
  • MohammadReza Shokouh, Akbar Safaie, Afagh Moattari, Jamal Sarvari * Pages 292-298
    Background & Objective

      Ovarian cancer is one of the most common cancers amongst women. The association of Human papillomavirus (HPV) and Epstein-Barr virus (EBV) with ovarian cancer is inconclusive; therefore, the aims of this study were to evaluate the frequency of HPV and EBV in malignant, borderline, benign and normal ovarian tissues.

    Methods

      In this case-control study, 205 Paraffin-embedded ovarian tissue specimens including 68 malignant, 27 borderline, 65 benign, and 45 normal tissues were included from December 2014 to January 2018 and subjected to DNA extraction. The β-globin gene was amplified using PCR to confirm the quality of the extracted DNA. The genomes of HPV (genotypes 16 and 18) and EBV were identified, using specific primers by PCR.

    Results

      The mean age of participants was 43.42 ± 15.4 years. The frequency of HPV was statistically significant between malignant versus benign (p =0.02) and control groups (p =0.002), but not with borderline tumor group (p =0.78). Amongst HPV infected samples, 1 (4.5%) and 14 (63.6%) samples were infected with types 16 and 18, respectively. Also 4 (18.2 %) samples were infected with both genotypes. Eleven samples including 7(10.3%) malignant, 1 (3.7%) borderline, 3 (4.6%) benign and none (0%) of normal control groups were infected with EBV, which was statistically different between malignant and the normal control group (p =0.03).

    Conclusion

      The results of our study showed the possible role of high risk HPVs as well as EBV in pathogenesis of ovarian cancer, and further studies are recommended to confirm these findings.

    Keywords: Epstein-Barr virus, Human papillomavirus, Ovarian Cancer
  • Maral Mokhtari *, Farzaneh Mostanbet, Saideh Nekooee Fard, Golsa Shekarkhar, Mozhdeh Sepaskhah, Maryam Sadat Sadati Pages 299-305
    Background & Objective

      Thiopurine drugs are considered as a treatment modality in various autoimmune disorders including pemphigus vulgaris (PV). These drugs are metabolized by an enzyme “Thiopurine S-methyl transferase” (TPMT). Various variants of this enzyme may have decreased activity leading to serious drug side effects. To investigate the phenotype and genotype of TPMT in PV patients receiving thiopurine drugs.

    Methods

      50 patients (29 women and 21 men) with pemphigus vulgaris treating with standard dose of Thiopurine drugs were selected. Sex, age, result of liver function test and complete blood count were recorded. Genotyping of two common non-functional allele (TPMT*2 and TPMT*3C) by Allele-specific and RFLP-PCR was performed. TPMT enzymatic level was determined by an ELISA based method.

    Results

      Of patients, 36 (72%) were found to have normal TPMT level; and 12, (24%) had higher level of enzyme and 2, 4% had low TPMT enzyme, but none of the patients showed mutant TPMT*2 and TPMT*3C alleles. None of the patients showed hepatotoxicity and bone marrow suppression.

    Conclusion

      The phenotypic assay based on ELISA method may have false positive and misleading results but genotyping using PCR-RFLP and allele specific PCR is accurate, simple and cost-effective and can be used in patients decided to undergo thiopurine treatment.

    Keywords: Allele specific PCR, PCR-RFLP, Thiopurine S- methyl transferase, Thiopurine drugs, ELISA test
  • Paulus Notopuro *, Jusak Nugraha, Budi Utomo, Harianto Notopuro Pages 306-312
    Background & Objective

      FLT3-ITD has been recently used as a molecular prognostic marker for risk classification in acute myeloid leukemia (AML) therapy. In this study we aimed to investigate the association of FLT3-ITD gene mutation with bone marrow blast cell count, CD34 expression as malignant cell burden, cyclin D1 and Bcl-xL expressions as indexes of cell proliferation and anti-apoptosis and human equilibrative nucleoside transporter 1 (hENT1) expression as cytarabine transporter during AML treatment.

    Methods

      We investigated FLT3-ITD mutations, bone marrow blast cell count, CD34, cyclin D1, Bcl-xL and hENT1 expression in bone marrow aspirates from 22 de novo AML patients in a cross sectional study.

    Results

      FLT3-ITD mutations were observed in 5 out of 22 de novo AML patients (22.7%). Patient with FLT3-ITD mutations had higher blast cell counts (79.5% vs 56.1%, p =0.004). In patients with FLT3-ITD mutations, CD34 and cyclin D1 expressions were higher (MFI 328.80 vs 25.78, p =0.003 and MFI 74.51 vs 57.15 p =0.005) than the patients without mutations. hENT1 expression in AML with FLT3-ITD mutation was lower (MFI 29.64 versus 56.32, p =0.0000) than in mutation-free AML. There was no significant difference in Bcl-xL expression between patients with and without mutations (p =0.61).

    Conclusion

      A significant association was found between FLT3-ITD gene mutations in AML patients with bone marrow blast cell count, CD34, cyclin D1 and hENT1 expressions, however no association was obtained with Bcl-xL expression. These findings support the role of such mutation in pathogenesis of AMLand its contribution in rearrangement of standard therapy with cytarabine in management of AML.

    Keywords: AML, Bcl-xL, Blast cell count, CD34, Cyclin D1, FLT3-ITD, hENT1
  • Alireza Abdollahi *, Abbas Shakoori, Hoda Khoshnevis, Mohammad Arabzadeh, Seyed Ali Dehghan Manshadi, Esmaeil Mohammadnejad, Dorsa Ghasemi, Maryam Safari Aboksari, Shaban Alizadeh, Vahid Mehrtash, Arezoo Eftekhar-Javadi, Masoomeh Safaei Pages 313-319
    Background & Objective

      A simple approach to prevent close contact in healthcare settings during the COVID-19 outbreak is to train patients to collect their own nasopharyngeal and oropharyngeal swabs and deliver them to medical laboratories to have them processed. The aim of our study was to compare lab technician- with patient- collected oropharyngeal and nasopharyngeal samples for detection of the coronavirus disease 2019 (COVID 19) using rapid real-time polymerase chain reaction (rRT-PCR).

    Methods

      Fifty adult patients with flu-like symptoms and radiologic findings compatible with atypical pneumonia who were admitted to the infectious diseases ward of Imam Khomeini Hospital Complex, Tehran, Iran, with a clinical diagnosis of COVID-19 from February 28 to April 27 of 2020 were randomly selected and entered in our study. Two sets of naso- and oropharyngeal swabs were collected, one set by a lab technician and the other by the patients, and the COVID-19 rRT-PCR test was performed.

    Results

      Of 50 selected cases, in seven patients all collected naso- and oropharyngeal swabs tested positive, and in 22 patients all samples tested negative for COVID-19 in rRT-PCR. Discrepancies between rRT-PCR results of lab technician- and patient-collected swabs were observed in 12 nasopharyngeal and 13 oropharyngeal specimens. Positive lab technician-collected and negative patient-collected samples were observed in 10 and 5 nasopharyngeal and oropharyngeal specimens, respectively. Negative lab technician-collected and positive patient-collected samples were observed in two and seven nasopharyngeal and oropharyngeal specimens, respectively. The overall percentage of agreement among both nasopharyngeal and oropharyngeal swabs taken by a lab technician and patients was 76% with a kappa value of 0.49 (p =0.001).

    Conclusion

      Based on our findings, lab technician-collected naso- and oropharyngeal swabs cannot be replaced by patient-collected ones with regard to COVID-19 rRT-PCR.

    Keywords: COVID-19, Oropharynx, Nasopharynx, Real-Time Polymerase Chain Reaction, Specimen collection
  • Mahdieh Mahboobi, Reza Mirnejad *, Hamid Sedighian, Vahhab Piranfar, Abbas Ali Imani Fooladi Pages 320-325
    Background & Objective

      Vibrio cholerae is a natural inhabitant of the environment and causes severe diarrhea ailments (cholera) that affects thousands of people each year worldwide. The most important virulence factors of this pathogen are cholera toxin (cholera toxin CT) and Type IV pili (toxin co-regulated pili TCP), which are encoded within the genome of the filamentous bacteriophage CTXφ. In the present study, according to researchers’ report on genotypic variations of cholera toxin, we evaluated the sequence of ctxB subunit obtained from 100 strains of patients infected with cholera in Iran.

    Methods

      The evaluation of genotype variations of cholera toxin was made by high-resolution melting curve analysis illustrating a single nucleotide change. Then, ctxB gene sequencing was performed. Through this analysis and the sequencing process, two standard samples were studied.

    Results

      Using serologic tests, all the strains analyzed in this study were identified to be in O1 serotype. However, there have been differences in sequences of ctxB as some were similar to V. cholerae O1 biovar El Tor str. N16961 while others were similar to the genotype of V. cholerae ATCC 14035. We did not observe any particular pattern within the process of mutation.

    Conclusion

      The analysis of the new samples of ctxB showed that they were potentially different. It seems that these complicated species were affected by a new genetic exchange of El Tor and classic genotypes.

    Keywords: ctxB, Vibrio cholerae, High-resolution melt analysis, Genotyping Techniques
  • AmirHossein Jafarian, Melika Kooshki Forooshani, Hossein Reisi, Nema Mohamadian Roshan * Pages 326-333
    Background & Objective

      Matrix metalloproteinases-9 (MMP-9) is one of the most important enzymes to breakdown extracellular matrix which plays a major role in tumor invasion and metastasis. This study aimed to determine tumor MMP-9 expression in non-small-cell lung carcinoma (NSCLC) and whether it is associated with histopathologic factors and has prognostic value to affect overall survival (OS).

    Methods

      The specimens of 92 patients with NSCLC diagnosis were included. Tumor sections were stained by immunohistochemistry method. Using scores for the percentage of cells positively stained and the intensity of staining, MMP-9 expression total score was classified as low-score (scores of 0 to 2), moderate-score (scores of 3 to 5), or high-score (scores of 6 or 7). OS was defined as the time interval since the diagnosis of NSCLC to the status at the last follow-up (dead or alive). The follow up period was up to 70 months.  

    Results

      About 74% of undifferentiated specimens (grade III tumors) showed high scores for MMP-9 expression which was significantly higher than moderately differentiated tumors (25% had high scores for MMP-9 expression) and well differentiated ones which did not have high scores (p <0.001). A total of 74 patients (80.4%) died during the follow-up period. Of this, 36% had high scores for MMP-9 expression. In contrast, none of the patients who were alive at the last follow-up had high scores for MMP-9 expression (p <0.001). Median OS was significantly lower in high score group (6 months) compared to moderate score (9 months) and high score group (15 months) (p <0.001).

    Conclusion

      MMP-9 expression may serve as a significant prognostic factor for mortality and overall survival in NSCLC. Undifferentiated tumors significantly express higher MMP-9 immunohistochemically.

    Keywords: Immunohistochemistry, Matrix metalloproteinase 9, Non-small-cell lung carcinoma
  • Farzaneh Nazari *, Zahra Dehghani Pages 334-337

    Ovarian cancer is the most lethal gynecologic malignancy. The surface epithelial tumor is the most common type of ovarian cancer. Among these, the mucinous tumors account for 10-15% of ovarian tumors. Mucinous ovarian tumors are among the most difficult ovarian neoplasms for surgical pathologists to interpret. Mucinous tumors sometimes coexist with other surface epithelial tumors. Therefore, making the accurate diagnosis of the mucinous tumors is essential. On the other hand, association of Brenner tumors with other neoplasms is rare. Ovarian Brenner tumor has always been discussed by pathologists as an enigmatic tumor, because of its rarity and disputed histogenesis. Here, we reported a case of large mucinous cystadenoma with Brenner component.

    Keywords: Brenner tumor, Mucinous tumor, Ovarian Cancer
  • Dorsay Sadeghian *, Farid Azmoudeh Ardalan, Simin Dashti Khavidaki, Nasir Fakhar Pages 338-341

    The occurrence of hepatotoxicity following etanercept (tumor necrosis factor-alpha antagonist) prescription, has been studied well. However, an acute hepatic failure leading to liver transplant as an adverse effect of this drug has not been reported in the literature. In this article, we are going to present a case of acute liver failure followed by liver transplantation, in a 32 years old man with a previous history of ankylosing spondylitis after etanercept administration. On pathologic examination of the explanted liver, extensive confluent necrosis in all liver segments, as well as prominent infiltration of a mixed population of inflammatory cells in portal tracts, were noted. This study urges the importance of close follow-up of patients receiving etanercept regarding liver complications. Further studies are required to assess the prevalence, risk factors, and outcome of these cases.

    Keywords: Etanercept, liver Transplantation, Hepatitis, Autoimmunity, Hepatic failure
  • Hedieh Moradi Tabriz *, Arezoo Eftekhar Javadi, Atiieh Zandnejadi Pages 342-345

    Thyroid gland metastatic tumors are rare in clinical practice. Clear cell RCC is one of common metastatic tumors to thyroid. We here reported a case of incidentally found clear cell renal carcinoma metastasis to the thyroid gland 3 years after nephrectomy, in the thyroidectomy procedure performed for the patient due to the thyroid enlargement caused by multinodular goiter. A 65-year-old Iranian man with a history of multinodular goiter referred to our surgery clinic for thyroidectomy because of compressive effects on the trachea. Patient had a history of nephrectomy due to clear cell RCC 3 years ago. After thyroidectomy, gross and histological examination of thyroid revealed clear cell renal carcinoma metastasis to the thyroid gland in the setting of a multinodular goiter. The diagnosis was confirmed by immunohistochemistry staining. Patients with multinodular goiter are more prone to present with metastasis to thyroid gland if they have a history of malignancy, especially renal cell carcinoma.

    Keywords: Renal cell carcinoma, Thyroid gland, Metastasis, Multinodular Goiter
  • Fereshteh Ameli *, Fatemeh Nili, Hana Saffar Pages 346-350

    One of the rare variants of extranodal large B-cell lymphoma is intravascular large B-cell lymphoma (IVLBCL). Characteristics of IVLBCL include intraluminal selective proliferation of atypical lymphoid cells in small to medium-sized vessels. The etiologic of IVLBCL is unknown, but due to the growth pattern of this tumor, it is speculated that IVLBCL is caused by a defect in homing receptor of tumor cells. IVLBCL can involve any organ but central nervous system, lungs, and skin are the most involved sites. IVLBCL does not usually involve lymph nodes. IVLBCL mainly occurs in the middle aged to elderly population with a slight male predominance. Generally, IVLBCL is aggressive and rapidly fatal if left untreated. We here reported two cases of IVLBCL who succumbed to the disease at initial phase of treatment to emphasize the difficulty in diagnosis of IVLBCL due to its exclusive intravascular growth pattern and fulminant clinical course.

    Keywords: Extranodal large B-cell lymphoma, Intravascular lymphoma, Fever of Unknown Origin (FUO)
  • Daniel Ribeiro *, Ingra Malacarne, Daniel Souza Page 351

    The aim of the letter to editor is to provide some comments regarding the manuscript of DehghanNezhad et al.(1) recently published in the Iranian Journal of Pathology titled “Micronucleus Assay of Buccal Mucosa Cells in Waterpipe (Hookah) Smokers: A Cytologic Study.” In this article, the authors were able to detect high frequencies of micronucleus in buccal mucosa cells of waterpipe smokers when compared to non-smokers.

    Keywords: Micronucleus Assay, Waterpipe Smoke, Buccal Mucosa
  • Noushin Jalayer Naderi * Pages 352-354

    Dear Editor, I was very pleased to find that the article” Micronucleus Assay of Buccal Mucosa Cells in Waterpipe (Hookah) Smokers: A Cytologic Study “(1) has attracted the attention of some readers and has created a few points for them. In my opinion, these points are good bases to overcome some concerns regarding micronucleus assay.

    Keywords: Micronucleus, Genotoxicity test, Buccal Mucosa