Iranian Journal Of Pathology
Volume:14 Issue: 4, autumn2019

Background & Malignant melanoma is the fatal cutaneous neoplasm which is curable by the early diagnosis. The expression of occludin protein which is an integral membrane protein is altered in an epithelial-to-mesenchymal transition. Although, recent studies provide sufficient evidence supporting the functional importance of occludin in cancer, the prognostic significance of occludin expression levels in melanoma remains obscure. The aim of this study was to determine occludin expression level and itscorrelation with clinicopathological features of the patients with melanoma.  The occludin mRNA level was compared between paraffin-embedded tissues of 40 patients with melanoma and 10 subjects with normal skin. The quality and quantity of the RNA was determined and occludin expression level was measured using Real-time PCR and ∆∆CT computational technique. Theoccludin mRNA level reduced five-fold in the melanoma patients compared to the control group (P=0.000). No significant difference was observed between male and female cases (P=0.533). No significant correlation was observed between occludin mRNA level, mitotic count (P=0.252), and Breslow levels (P=0.171) We can conclude that down-regulation of occludin expression in the patients with melanoma is a hallmark of cancer progression and it might be used as a prognostic factor. No significant correlation was found between occludin gene expression and clinicopathological characteristics including Clark level, Breslow staging, mitotic count, age and gender (P<0.05).

Background & Malignant breast tumors, which are one of the most important deadly cancers in women, like many other cancers, are proposed to be related to viruses etiologically. Proper management of breast carcinoma necessitates an identification of the etiological factors. Human Papillomavirus is considered to have an etiological role in breast carcinoma. We carried out this study to find out if Human Papillomavirus-DNA is present in the malignant and benign breast tissue in our patients. Seventy five paraffin-embedded breast cancer tissues and 75 normal breast tissues and benign breast lesions were examined in this study (case-control) to look for Human Papillomavirus-DNA employing Nested Polymerase Chain reaction. The tissues were examined over a period of ten years in the pathology department of the Pathobiology Laboratory Center of Tehran. No Human Papillomavirus-DNA was found in any of the malignant or control group specimens. Our results showed no evidence of Human Papillomavirus in cancerous and benign tissues, which is consistent with some other studies in English medical literature. More investigations using more specimens from different parts of the country are required to confirm the presence or absence of any connection between Human Papillomavirus and development of breast carcinoma in Iran.

Background & Methicillin-resistant Staphylococcus aureus (MRSA) is reported as one of the important bacterial causes of burn wound infections. This study was carried out to investigate molecular characterization of community-associated MRSA (CA-MRSA) isolated from Iranian burn patients. A total of 31 isolates of S. aureus were collected fromthe Motahari Burns Hospital (Tehran, Iran) in 2016. All isolates were collected from outpatients and inpatients within 48 hours of admission. The mecA, pvl, tsst-1, hla-α, and psmα genes detecting, SCCmec, agr and PFGE typing were done. A total of 13 (41.9%) isolates were cefoxitin-resistant and mecA-positive, which were considered as MRSA. The SCCmec typing MRSA strains revealed type II in 1 (7.7%), type III in 9 (69.2%), and other types in 3 isolates (23.7%) cases. The agrtyping of all 31 isolates showed that 14 (45.2%), 1 (3.2%), 6 (19.4%), and 10 (32.3%) strains belonged to agr groups 1, 3, 4, and unknown type, respectively. The pvl, tsst-1, hla-α, and psmα genes were positive in 3 (9.7%), 4 (12.9%), 21 (67.7%), and 31 (100%) isolates, respectively. Considering the cut-off values of ≥50%, 3 groups of related isolates (cluster A1, B1, and C1) in PFGE study were observed. The MRSA strains of this study were initially isolated as Community-associated S. aureus (CA-MRSA); however molecular characterization showed that a significant proportion of them had hospital-associated MRSA (HA-MRSA) features. Therefore, it is likely that the HA-MRSA strains are spread among the community.

Background & Papillary thyroid cancer (PTC) is considered to be the most common type of thyroid malignancies. Epigenetic alteration, in which the chromatin conformation and gene expression change without changing the sequence of DNA, can occur in some tumor suppressor genes and oncogenes. Methylation is the most common type of epigenetic alterations that can be an excellent indicator of PTC invasive behavior. In this research, we determined the promoter methylation status of four tumor suppressor genes (SLC5A8, RASSF1, MGMT, and DNMT1) and compared the results of 55 PTC cases with 40 goiter patients. For methylation, we used the methylation-sensitive high resolution melting (MS-HRM) assay technique. The resulting graphs of each run were compared with those of 0%, 50%, and 100% methylated controls. Our data showed that the promoter methylation of SLC5A8, Ras association domain family member 1(RASSF1), and MGMT were significantly different between PTC tissue and goiter with P-value less than 0.05. The most significant differences were observed in RASSF1; 77.2% of hyper-methylated PTC patients versus 15.6% hyper-methylated goiter samples (P<0.001). RASSF1 promoter methylation can be a PTC genetic marker. RASSF1 promoter methylation is under the impact of the methyltransferase genes (DNMT1 and MGMT), protein expression, and promoter methylation.

Background & In Triple-Negative Breast Cancers (TNBCs), estrogen receptor (ER), progesterone receptor (PR) and HER2/neu genes are not expressed. Fibroblastic Growth Factor Receptor-1 (FGFR1) gene product is a protein that acts as a receptor of thyrosin kinase. It plays a role in the proliferation, differentiation, and migration of malignant cells. The objective was to evaluate the possible relation between FGFR1 over-expression and amplification in TNBCs and other clinicopathological variables.  In this cross sectional study, purposive sampling was used to collect eighty-four TNBC specimens from mastectomy specimens collected between 2013 and 2017. Tissue microarrays were evaluated for FGFR1 over-expression and amplification respectively by immunohistochemistry (IHC) staining and real time Polymerase Chain Reaction (PCR). The needed clinical and paraclinical information were obtained from patients’ files. To analyze the correlation among prognostic factors, we used a wide range of different statistic methods, namely Chi-square test, independent t-test, Fisher's exact test, and ANOVA. FGFR1 over-expression was found in 15 of the 84 samples (17.9%). FGFR1 gene amplification was observed in 33.3% (28 of 84) of the samples. We found no association between FGFR1 and clinicopathological parameters, including tumor grade, stage, and patient survival (P>0.005). FGFR1 over-expression and amplification may not be related to clinicopathological parameters, namely age, stage, and grade of the cancer not to mention TNBC survival. Using FGFR1 as a prognostic factor in TNBCs requires further study.

Background & A main contest in chemotherapy is to obtain regulator above the biodistribution of cytotoxic drugs. The utmost promising strategy comprises of drugs coupled with a tumor-targeting bearer that results in wide cytotoxic activity and particular delivery. The B-subunit of Shiga toxin (STxB) is nontoxic and possesses low immunogenicity that exactly binds to the globotriaosylceramide (Gb3/CD77). Gb3/CD77 extremely expresses on a number of human tumors such as pancreatic, colon, and breast cancer and acts as a functional receptor for Shiga toxin (STx). Then, this toxin can be applied to target Gb3-positive human tumors. In this study, we evaluated DT390-STXB chimeric protein as a new anti-tumor candidate via genetically fusing the DT390 fragment of DT538 (Native diphtheria toxin) to STxB. This study intended to investigate the DT390- STxB fusion protein structure in silico. Considering the Escherichia coli codon usage, the genomic construct was designed. The properties and the structure of the protein were determined by an in silico technique. The mRNA structure and the physicochemical characteristics, construction, and the stability of the designed chimeric protein were analyzed using computational and bioinformatics tools and servers. Hence, the GOR4 and I-TASSER online web servers were used to predict the secondary and tertiary structures of the designed protein. The results demonstrated that codon adaptation index (CAI) of dt390-stxB chimeric gene raised from 0.6 in the wild type to 0.9 in the chimeric optimized gene. The mfold data revealed that the dt390-stxB mRNA was completely stable to be translated effectively in the novel host. The normal activity of the fusion protein determined by considering the secondary and tertiary structure of each construct. Energy calculation data indicated that the thermodynamic ensemble for mRNA structure was -427.40 kJ/mol. The stability index (SI) of DT390-STxB was 36.95, which is quite appropriate to preserve the stability of the construct. Ultimately, the DT390-STxB was classified as a steady fusion protein according to the Ramachandran plot. Our results showed that DT390-STXB was a stable chimeric protein and it can be recruited as a candidate of novel anti-tumor agents for the development of breast cancer treatment.

Background & Squamous cell carcinoma (SCC) is the second most common non-melanoma skin cancer that may be caused by Human papillomavirus (HPV), especially in immunosuppressed patients. However, the role of the mucosal types of HPV in SCC patients with normal immunity has not been extensively confirmed. The aim of this study was to investigate the association of some high-risk mucosal types of HPV with cutaneous SCC in an Iranian population.  Sixty-five formalin-fixed, paraffin-embedded tissue specimens with a diagnosis of cutaneous SCC as the case group and sixty-five healthy skin specimens as the control group were included in our case-control study. Genomic DNA was extracted from tissue samples and then PCR was used for the detection of HPV genotypes by a commercial kit. Our data revealed that 6 out of 65 SCC samples (9.2%) were infected by high-risk mucosal types of HPV whereas none of the 65 control samples were infected by the mentioned HPVs. Statistical analysis showed a significant association between these types of HPV infection and SCC risk in our studied population (P=0.028). These findings suggested that some high-risk mucosal types of HPV are significant risk factors for cutaneous SCC.

Abstract Colorectal cancer is the third most prevalent malignancy with high mortality rate, necessitating markers that predict survival and guide the treatment. Previous studies have examined the immunohistochemical expression of Bcl-2, an apoptotic marker, in colorectal carcinoma, but results have been contradictory. To evaluate the histopathological features of colorectal carcinoma, analyze the immunohistochemical expression of Bcl-2, and to find out statistical association of Bcl-2 expression with certain prognostic factors histopathologic type, grade and stage. This prospective study was conducted on the colectomy specimens of colorectal carcinoma, over a period of two years. The tumor morphology and Bcl-2 status were evaluated by immunohistochemistry in each case. The study included 58 cases, with mean patient age of 47.07 years and male: female ratio of 1.89:1. Bcl-2 positivity was seen in 32.7% of cases. Weak, moderate, and strong expression of Bcl-2 was seen in 12.1%, 12.1%, and 8.5% of cases respectively. Even though early stages of colorectal carcinoma showed greater frequency of Bcl-2 expression than advanced stages (36.3% versus 28%), this association was not statistically significant. Lack of statistically significant correlation between Bcl-2 immunohistochemical expression and prognostic parameters like tumor grade and stage, suggests that Bcl-2 immunoexpression may not be a significant prognostic marker in colorectal carcinoma. Key words: Colorectal carcinomas; Immunohistochemistry; Prognostic factors.

Background &

Endometrial carcinoma (EC) has been traditionally classified into two distinct categories of low-grade and high-grade. Type I (low grade) EC, which constitutes the majority of cases, is linked to estrogen-related molecular pathways. But type II (high-grade) EC accounts for 10-20% of cases and behaves in an aggressive way. Pathologic and biological features of type II EC have not been fully elucidated yet. Several investigations have demonstrated HER2/neu expression and amplification in type II EC, especially papillary serous carcinoma (PSC).This study assessed HER2/neu expression in high-grade EC as well as its association with other clinical and histopathological prognostic factors.

In this cross-sectional study, we performed HER2/neu immunohistochemical (IHC) staining in 37 high-grade EC cases with histological diagnostic categories of PSC (n=23), clear cell carcinoma (CCC) (n=9), and carcinosarcoma with high-grade carcinomatous component (PSC, CCC, grade 3 endometrioid carcinoma, or unclassified high-grade adenocarcinoma) (n=5). All patients were followed for 2-9 years in order to evaluate their disease-free survival (DFS) and overall survival (OS) during study period (2005-2014).

HER2/neu IHC staining was positive in 12 patients (32.4%) including 8/23 (34.8%) PSC, 2/9 (22.2%) CCC, and 2/5 (40%) carcinosarcoma cases. There was no statistically significant difference between HER2/neu expression and DFS or OS of the patients (P>0.05).

We observed that HER2/neu is expressed in one-third of high-grade ECs. This ancillary test is supportive in follow-up of patients with high-grade ECs.

Background & Diabetic foot ulcer (DFU), is one of the most frequent causes for hospitalizations in patients with diabetes. A major problem in the treatment of DFU is the increased-incidence of methicillin-resistant Staphylococcus aureus (MRSA). The aim of this study was to determine the SCCmec types of MRSA isolates and their epidemiology among patients with diabetes. This study was carried out on 145 diabetic patients with DFUs. The antibiotic susceptibility tests (ASTs) were performed using the disk diffusion method and E-test technique. SCCmec typing was done by multiplex PCR. Moreover, the presence of virulence toxin genes, including pvl and lukED was detected by PCR assay. In 145 samples from which S. aureus was predominantly isolated, 19.48% were MRSA. Analysis of MRSA isolates revealed that the most prevalent SCCmec type was type IV (46.7%) followed by type III (30.0%) and type V (20.0%). One strain (3.3%) was untypeable. The prevalence of pvl and lukED was 56.7% and 100%, respectively. The high prevalence of MRSA in DFUs represents the high levels of antibiotic usage among patients with diabetes. In this study, resistance to other important clinical antibiotics was detected among MRSA isolates. The high proportion of SCCmec type IV and V strains, even in former hospitalized patients, indicates the entrance of these clones to the clinical setting.

Rhabdoid papillary meningioma is an uncommon aggressive variant of meningioma which has the potential to metastasize and spread throughout the brain and even out of the cranium. Herein, we present recurrence of the brain tumor in a 26-year-old woman. The patient had history of the surgery for two lesions in the right temporal lobe and the left cerebellopontine angle. Imaging showed three lesions in the right temporal lobe, the right occipital horn wall, and the left cerebellopontine angle. These radiologic findings were mostly suggestive of atypical meningioma. In the surgical view, the mass was solid-cystic reddish Cauliflower-shaped in the right temporal lobe attaching to the temporal horn. The microscopic examination showed a cellular neoplasm with the sheet-like and papillary growth pattern. Individual cells had vesicular nuclei some with prominent nucleoli and eosinophilic cytoplasm. The areas of the tumor cells showed round eccentric nuclei and prominent nucleoli with eosinophilic cytoplasm. Immunohistochemistry studies showed diffuse positivity of tumor cells with Vimentin, EMA, and S100. The overall clinical, radiological and histopathological examinations were compatible with high grade rhabdoid-papillary meningiomas. In the present case study, we discuss imaging and histomorphological features of this rare entity of meningiomas.

The most usual form of the endocrine carcinoma is thyroid cancer (TC). In addition to papillary thyroid carcinoma (PTC), recent studies revealed incidence of RET/PTC rearrangement in other tumors, like Hürthle cell carcinoma (HCC) and even in non-carcinomatous disorders like Hashimoto's thyroiditis. Here, we present a case with concurrence of papillary thyroid carcinoma and Hürthle cell carcinoma. A 60-year-old woman referred to our hospital with a mass in her neck. Physical examinations revealed painful swelling in the thyroid. Ultrasonographic examination showed two hypoechoic nodules in the right lobe. Hürthle cell variant papillary carcinoma was suggested in the cytology report of the fine needle aspiration. Permanent histopathological diagnosis was co-existence of papillary thyroid carcinoma and Hürthle cell carcinoma. The patient was asymptomatic in 14 months follow up. Concurrence of papillary carcinoma and Hürthle cell carcinoma is a rare form of thyroid malignancies, with doubtful cytogenetic findings and biological behaviors. The results showed that it is necessary for the surgeons and pathologists to be aware of lesions for the optimal diagnostic and therapeutic interventions. Also, it is vital to follow up patients with the Hashimot’s thyroiditis who have multiple nodules to detect occult thyroid cancers and decide for better therapeutic programs.