Molecular Pathology
Fatemeh Hoseini Tabatabaie; Seyed Younes Hosseini; Seyed Mohammad Ali Hashemi; Akbar Safaie; Jamal Sarvari
Abstract
Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical ...
Read More
Background & Objective: Epstein-Barr virus nuclear antigen-1 (EBNA1) is one of the most important proteins of Epstein-Barr virus (EBV) that might be mutated in various related cancers. The purpose of this study was to compare EBNA1 mutations in the C-terminal region between patients with cervical and ovarian cancer and healthy individuals.Methods: As test and control groups, 18 EBV-positive paraffin-embedded samples of cervical and ovarian cancer and 10 age- and gender-matched healthy volunteers who did not have cancer but were EBV-positive were both used. Utilizing a commercial DNA extraction kit, total DNA was extracted following deparaffinization. The entire C-terminal region of the EBNA1 sequence was amplified using an in-house nested PCR. Phylogenetic analysis and Sanger sequencing were used to analyze the sequences using MEGA 7 software and through NJ method.Results: Sequence analysis revealed that the P-Ala subtype of EBNA1 was present in all samples. In two and one samples, respectively, of cervical cancer patients, the mutations A1887G and G1891A were found. The G1595T mutation was also detected in four sequences taken from ovarian cancer patients. No statistically significant difference could be found between the frequency of mutations in patients and controls (P>0.05). No known amino acid substitutions were found in the USP7-binding region and the DBD/DD domain.Conclusion: The findings showed that P-Ala is the predominant EBV subtype across all samples. Additionally, as the sequence of EBNA1's C-terminal region is so stable, it's possible that it had little impact on the pathogenesis of ovarian and cervical malignancies. It is advised to conduct additional research to verify these findings.
Molecular Pathology
Seyed Amir Miratashi Yazdi; Elham Nazar
Abstract
The etiology of parathyroid carcinoma (PC) is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin ...
Read More
The etiology of parathyroid carcinoma (PC) is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. The management of PC is challenging for clinicians. The complexity of molecular phenotypes increases with tumor aggressiveness. Lack of parafibromin on immunohistochemistry staining and HRPT2 mutation present capable consequences in differentiating carcinoma from adenoma. Lack of parafibromin expression, the gene product of HRPT2 is now used as a diagnostic, prognostic and predictive marker for parathyroid carcinoma. The epigenetic alteration, for example, DNA methylation and modifications in the chromatin structure, are known as significant events that are the reason for parathyroid tumorigenesis. We suggest that adjuvant genetic and epigenetic target therapy should be considered in treating PC patients.
Dermatopathology
Fatemeh Sari Aslani; Akbar Safaee; Mozhgan Akbarzadeh Jahromi; Leila Karami
Abstract
Background & Objective: Acral melanoma (AM) is a common type of cutaneous melanoma that occurs in the skin of the palms, soles, and nail beds. This malignancy, like other types of cancer, has different genetic alterations. To date, despite decades of research the roles of oncogenic BRAF mutations ...
Read More
Background & Objective: Acral melanoma (AM) is a common type of cutaneous melanoma that occurs in the skin of the palms, soles, and nail beds. This malignancy, like other types of cancer, has different genetic alterations. To date, despite decades of research the roles of oncogenic BRAF mutations in the pathogenesis of AM has not been fully clarified. The present study was designed to identify V600E mutation in patients with AM from the south of Iran. Methods: The samples were collected from the pathology lab archive of Shiraz University of Medical Sciences (2015-2020). A total of 41 patients with primary invasive AM underwent excisional biopsy or amputation were collected to evaluate BRAF V600E mutation using Polymerase Chain Reaction (PCR) and Sanger sequencing.Results: Total number of 41cases (21 male and 20 female) and age range of 34-87 years were enrolled. The histological subtypes were 24 acral lentiginous melanomas (ALM), 10 cases of nodular melanoma (NM), and 7 cases of superficial spreading melanoma (SSM). In our study, only one case (a 44-year-old male with nail bed AM and the histological subtype of acral lentigenous melanoma) showed BRAF-V600E mutation. Conclusion: These findings suggest that the population of our interest showed a very low prevalence of this mutation providing novel insights into the pathobiology of AM and its related treatment.
Microbiology
Zoheir Heshmatipour; Nasibeh Arabameri; Shima Eftekhar Ardebili; Zeinab Jafari Bidhendi
Abstract
Background & Objective: Pseudomonas aeruginosa is an opportunistic pathogen and one of the most common causes of nosocomial infections. This bacterium's antibiotic resistance to the common fluoroquinolone antibiotics, especially ciprofloxacin, is due to mutations in the gyrA and parC genes. This ...
Read More
Background & Objective: Pseudomonas aeruginosa is an opportunistic pathogen and one of the most common causes of nosocomial infections. This bacterium's antibiotic resistance to the common fluoroquinolone antibiotics, especially ciprofloxacin, is due to mutations in the gyrA and parC genes. This study aimed to investigate the effect of the mutation in (gyrA, parC) on ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa.Methods: A total of 140 clinical samples were collected from hospitals. The samples were identified by standard biochemical tests, and the antibiotic resistance was investigated by the disk diffusion method. DNA was extracted from 30 isolates, and PCR was performed. PCR-sequencing was carried out to assess gyrA and parC mutations in drug-resistant isolates. NCBI-Blast and MEGA7 software was used to analyze the nucleotide sequences.Results: 30 clinical isolates were 80% resistant to ciprofloxacin; meanwhile, in 21 samples, mutations were observed. 87/5% of mutations were related to gyrA (Thr83 → Ile), 79/16 % parC (Ser87 → Leu), and 4/18% (Glu91 → Lys). The antibiotic resistance to ciprofloxacin and mutations in gyrA and parC genes in resistant isolates are significantly related to each other (P<0.05). Conclusion: The mutations in the gyrA and parC genes play an essential role in resistance to ciprofloxacin in clinical isolates of Pseudomonas aeruginosa.
Molecular Pathology
Sahand Mohammadzadeh; Zahra Jowkar; Mitra Mirzaee; Bita Geramizadeh
Abstract
Background and Objective: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about ...
Read More
Background and Objective: Epidermal growth factor receptor (EGFR) gene mutation, especially in exons 18 to 21, is an important predictor of the response rate of lung adenocarcinoma to tyrosine kinase inhibitors. There are variable reports from Asian and European countries, as well as North America, about the frequency of the EGFR mutation in lung adenocarcinoma, yet molecular study about this incidence has been published from Iran. In this study, we investigated the frequency of this mutation in our center, which is the largest referral center in the south of country. This report will be the first published article about EGFR mutational analysis from Iran.Methods: During the study period (September 2011 till September 2016) i.e. 5 years, there have been 50 cases of pathologically-confirmed lung adenocarcinoma. These cases underwent mutational analysis for exons 18 to 21 of the EGFR gene by PCR and DNA sequencing. All demographic findings were also extracted from the patients’ charts and recorded.Results: There were 30 male and 20 female patients, with an average age of 58 years. The overall frequency of EGFR mutation was 28% (14 out of 50). The most common mutation was Del 19 (10 of 14, 71.4%), 3 mutations were found in exon 20 and one mutation was found in exon 21. EGFR mutations were more frequent in women than in men (30% versus 26.7%) and in nonsmokers than in smokers (37.9% versus 14.3%).Conclusion: Lung adenocarcinoma with EGFR mutation shows strong association with female non-smokers. Our results showed an intermediate frequency of this mutation, which was higher than results from Western countries and lower than most Asian countries.
Maryam Ghasemi; Laleh Vahedi-larijani; Omid Emadian; Jamshid Yazdani; Ahmad Sajadianfar; Saeid Abediankenari
Abstract
Background & Objective: This study was designed for the first time for the detection of mutant BRAF V600E and its correlation with clinicophathologic features in a sample of Iranian patients with pathologically proved pigmented skin neoplasms.Methods: 82 paraffin-embedded blocks, including melanocytic ...
Read More
Background & Objective: This study was designed for the first time for the detection of mutant BRAF V600E and its correlation with clinicophathologic features in a sample of Iranian patients with pathologically proved pigmented skin neoplasms.Methods: 82 paraffin-embedded blocks, including melanocytic nevi, malignant melanoma, Basel cell carcinoma, and squamous cell carcinoma were evaluated for BRAF V600E expression by immunohistochemistry in the patients admitted to Ibn Sina Hospital, in the city of Sari, Mazandaran province, North of Iran. The evaluation of immunohistochemical staining was performed by two of the authoring pathologists, and staining intensity was graded from negative (0), weak (1+), moderate (2+) to strong (3+). If twenty percent (or greater) of the tumor cells showed modest to strong cytoplasmic immunoreactivity (score 3+), the neoplasm was considered positive for this tumor marker.Results: Among 82 studied patients, 12 cases (60%) of the malignant melanoma group revealed a high intensity of immunostaining for BRAF V600E, while a significant expression of this marker did not occur in the other investigated skin neoplasm. A great relation between BRAF (V600E) expression and the histologic type of skin cancer was noted. No significant relationship with other parameters such as gender, age, and the grade differentiation of the non-melanoma skin cancer was found. BRAF V600E was weakly correlated with the Clark level of cutaneous malignant melanoma.Conclusion: This data provided further
