Iranian Journal of Pathology最新文献

Background & objective: Breast cancer (BC) can be categorized into 4 groups based on molecular and pathological evidence: Luminal A, Luminal B, HER2+ tumors, and triple-negative breast cancer (TNBC). TNBC has a poorer survival rate and a higher chance of recurrence and metastasis compared to other BC types, primarily due to its challenging treatment course. Claudin 4 (CLDN4), a transmembrane protein in tight junctions between cells, has been linked to poor prognosis and faster disease progression in these malignancies.

Methods: Patients previously diagnosed with TNBC and tested for CLDN4 overexpression were contacted for follow-up and to determine disease outcomes. The current health status, cause, and time of death (if applicable) were recorded. Patient files were accessed to obtain information on age, tumor size and grading, lymph node involvement, metastasis, Ki67, and CLDN4 expression.

Results: Patients with high CLDN expression showed a significantly lower mortality rate. However, after controlling for other covariates, the hazard ratio (HR) was 0.48 (95%CI= [0.13 - 1.27]) in the crude model for survival, 0.54 (95%CI = [0.2 - 1.43]) when adjusted for age at diagnosis, and 0.58 (95%CI = [0.18-1.82]) when adjusted for other covariates. CLDN4 was also not correlated with tumor metastasis (HR=0.64, p=0.203, in the crude model; HR=0.52, p=0.409, when adjusted for other covariates). Patients in the CLDN4 high group had a significantly higher number of tumors >2cm.

Conclusion: Although previous studies have shown that CLDN4 overexpression worsens TNBC prognosis and increases metastasis or recurrence, the current study found no such association.

Background & objective: Rhizopus arrhizus, a major contributor to COVID-19-associated mucormycosis (CAM) globally. Nanoliposomal amphotericin B (NLAmB) presents a promising approach due to its enhanced drug delivery and reduced side effects. This study aimed to assess the in vitro antifungal susceptibility of NLAmB against R. arrhizus isolated from CAM patients.

Methods: Thirty-nine R. arrhizus isolated from CAM patients were identified through phenotypic characterization, MALDI-TOF, and the internal transcribed spacer rDNA region (ITS) sequencing approaches. Antifungal susceptibility testing (AFST) for NLAmB, amphotericin B (AmB), posaconazole (PSC), and isavuconazole (ISC) was conducted through broth microdilution methods according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) standard E.DEF 9.4. Results were analyzed for MIC ranges, MIC50, MIC90, and distributions.

Results: NLAmB demonstrated superior in vitro efficacy against R. arrhizus (MIC50/90, 0.063/0.25 μg/ml) compared to AmB, PSC, and ISC. PSC exhibited notable activity (MIC range: ≤0.031 - ≥16 μg/ml).

Conclusion: The study emphasized NLAmB's sustained activity, making it a potential alternative to LAmB. Further exploration and clinical correlation are warranted to validate NLAmB in CAM treatment.

Background & objective: There is controversy whether eosinophils are involved in the pathogenesis of psoriasis. This study aims to assess the quantity of eosinophils in pathological specimens obtained from individuals diagnosed with psoriasis.

Methods: cross-sectional and retrospective study 91 skin samples were obtained from patients with diagnosis of psoriasis. Two experienced dermatologists thoroughly reviewed the specimens' demographic characteristics, clinical features, and pathological attributes. Subsequently, eosinophils were counted within all microscopic fields, utilizing a magnification of 200.

Results: Eosinophils were present in approximately 70.3% of the examined samples, with a mean eosinophil count of 2.42±0.63. Although no significant correlation was observed between the clinical subtype and the average eosinophil count, eosinophils were most commonly detected in the cases presenting generalized pustular psoriasis (100%) and vulgaris types (71.11%). Notably, patients exhibiting Munro's microabscess and dilated papillary dermal blood vessels exhibited a significantly higher number of eosinophils (P=0.007 and P=0.039, respectively). Additionally, a notable association was identified between presence of spongiosis, and eosinophil counts in the pathological samples (P=0.04).

Conclusion: Presence of eosinophils may not contradict a diagnosis of psoriasis. Furthermore, a notable association may be observed between the number of eosinophils and presence of spongiosis, dilated dermal papillary vessels, and Munro's microabscess.

Background & objective: miR-196b, HOXA9, GFI1, and PIM1 are key factors involved in cellular signaling pathways that contribute to the pathogenesis of malignancies, including acute myeloblastic leukemia (AML). Given their critical roles in AML progression, the present study aimed to investigate the gene expression levels of HOTAIRM1, miR-196b, HOXA9, GFI1, and PIM1 in AML patients compared to healthy controls.

Methods: A total of 30 AML patients and 10 healthy volunteers were enrolled in this study. Peripheral blood and bone marrow mononuclear cells were isolated using Ficoll-Paque density gradient centrifugation. Gene expression levels of HOTAIRM1, miR-196b, HOXA9, GFI1, and PIM1 were assessed using real-time quantitative PCR (RQ-PCR). Statistical analyses were performed using Student's t-test, one-way ANOVA, and Pearson correlation tests.

Results: The expression levels of HOTAIRM1, miR-196b, HOXA9, and GFI1 were significantly elevated in AML patients compared to healthy controls. Furthermore, t-test analysis revealed that the expressions of HOTAIRM1, HOXA9, and GFI1 significantly differed between AML-M3 and non-M3 AML subtypes.

Conclusion: These findings suggest that the investigated markers, particularly HOTAIRM1, HOXA9, and GFI1, may serve as potential clinical biomarkers for monitoring AML progression and could be valuable targets for early detection or therapeutic intervention.

COVID-19-associated pulmonary aspergillosis (CAPA) is a complication of COVID-19. Galactomannan (GM) is a non-invasive test used to diagnose invasive aspergillosis. We collected the existing studies on the diagnostic value of GM to determine a GM level for predicting CAPA. All articles on the value of GM in CAPA diagnosis published until November 2023 were reviewed. The main databases were searched using the following keywords: "aspergillus", "aspergillosis", "SARS-CoV-2", "COVID", "2019 ncovnCOV", "novel coronavirus", "COVID-19", "galactomannan", and "CAPA". Studies with reported levels of serum or BAL GM were included. Patients were classified into two groups: non-confirmed and proven aspergillosis. Finally, the receiver operating characteristic (ROC) curve analysis was used to determine a GM level to predict the likelihood of CAPA. A total of 26 articles were selected, of which 239 patients were included. A count of 123 patients (50%) were in the non-confirmed group and 124 (50%) patients were proven. The median serum GM was 0.51 in the non-confirmed group and 0.47 in the proven group (p= 0.73). The level of GM in BAL fluid was 0.10 in the non-confirmed and 2.80 in the proven group, which was statistically different (p<0.001). With 81.3 % sensitivity and 79.5% specificity, the BAL GM cut-off was 1.01 ODI. The results showed that BAL GM ≥1.01 can be used to predict CAPA. Serum GM did not show any predictive value in diagnosing CAPA. However, BAL GM level can be a reliable diagnostic test in patients with CAPA.

Background & objective: Breast cancer (BC) is the most common type of malignant neoplasm and is the primary cause of mortality among women aged 45 to 55 years. Studies indicate that cancer displays irregular metabolic patterns in contrast to normal tissue. Furthermore, there is compelling evidence supporting the significant role of peroxisomes in the intricate metabolic processes of cancer. Peroxisomal biogenesis factors (PEXs), which are peroxisomal proteins, control activities such as the degradation and biogenesis of peroxisomes. Hence, the correlation between peroxisomal biogenesis factor expression and BC was explored, to introduce key proteins and potential biomarkers by analyzing.

Methods: This study utilized UALCAN, GenExMiner v4.8, Metascape, STRING, TIMER, the Kaplan-Meier plotter, The Human Protein Atlas, MirTarBase, and cBioportal.

Results: The transcriptional levels of PEX6/7/10/11B/13/16 in BC tissues were significantly elevated, whereas the transcriptional levels of PEX2/3/5/11A/12/19 were significantly reduced. High expression levels of PEX 2/3/10/12/11G /26/13/16/14 were significantly related to shorter relapse-free survival, and higher mRNA expression of PEX 11B/11G/11A/12/19 was significantly associated with longer overall survival of BC patients. We identified has-miR-4318 and has-7106-3p as more correlated miRNAs with the PEX family.

Conclusion: Our results may provide novel insights for the selection of therapeutic targets and prognostic biomarkers for BC.

Background & objective: Melanoma is one of the most common types of skin cancer with an annually increasing mortality rate. Cyclooxygenase-2 (COX-2) plays an imperative role as a cancer biomarker in the biosynthesis of prostaglandin and thromboxane during inflammatory reactions. Its overexpression has been demonstrated in various cancer types, including melanoma. However, its clinicopathological association with melanoma is controversial. We aimed to immunohistochemically evaluate COX-2 expression in malignant melanoma (MM) tumors.

Methods: In this cross-sectional retrospective study, blocks from patients with MM who were referred to Rasool-Akram and Razi hospitals between 2011 and 2020 were collected and immunohistochemically evaluated using COX-2 antibody. The intensity and percentage of COX-2 expression was determined in tumoral tissues, and its association with clinical and histological features of patients were evaluated.

Results: A total of 39 patients diagnosed with MM were included in this study, of whom 20 (51.3%) were male and 19 (48.7%) were female, with an average age of 57.28 ± 14.37 (range 14-87 years). The most common histological subtypes were acral melanoma (30.8%) and nodular melanoma (20.5%). The most common locations of tumor involvement were the lower (33.3%) and upper limbs (23.1%). Ulcers and vascular-lymphatic invasion were observed in 33.3% and 5.1% of cases, respectively. 38.5% of tumors were in level IV according to Clark's level. Elastosis was present in 13% of samples. Approximately 87% of MM samples showed COX-2 expression, 61.5% of which were strong. There was a significant association between COX-2 expression and tumor location (P = .04).

Conclusion: Our findings highlight that the COX-2 protein is considerably expressed in MM tumors. Therefore, therapeutic strategies with the aim of targeting COX-2 might be considered in the prevention or treatment of MM. However, it remains to be explored whether COX-2 might be a prognostic marker of MM.

Background & objective: Subtyping non-small cell lung carcinoma (NSCLC) into adenocarcinoma (ADC) and squamous cell carcinoma (SCC) is crucial for selecting appropriate molecular tests, as driver mutations are often subtype-specific. This study aimed to evaluate the utility of TTF-1, Napsin A, p40, and p63 immunohistochemical (IHC) markers in subtyping NSCLC on small biopsies, with the goal of identifying a minimal marker panel.

Methods: This retrospective, cross-sectional study was conducted at Kasturba Medical College, Mangalore, from January 2014 to December 2020. All NSCLC cases diagnosed during the study period were included. Immunohistochemical expressions of TTF-1, Napsin A, p40, and p63 were evaluated and correlated with morphological findings.

Results: Ninety-five NSCLC cases were included: adenocarcinoma (n = 35), squamous cell carcinoma (n = 57), and NSCLC-not otherwise specified (NOS) (n = 2). IHC reclassification based on marker expression resulted in six ADC cases retyped as SCC and eight SCC cases retyped as ADC. TTF-1 and Napsin A expression were significantly associated with adenocarcinoma (p < 0.001), while p40 and p63 expression were significantly associated with SCC (p < 0.001).

Conclusion: IHC is essential in overcoming the diagnostic limitations of small biopsy specimens, especially in morphologically heterogeneous tumors. A minimal panel comprising TTF-1 and p40 is sufficient for accurate subtyping of NSCLC and can help preserve tissue for downstream molecular testing.

Background & objective: This study aimed to elucidate the complex interplay between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and the expression of key inflammatory cytokines interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-1 beta (IL-1β).

Methods: A cross-sectional study was conducted involving 100 participants categorized into four groups: IR only (n=30), T2DM without IR (DM-IR, n=20), T2DM with IR (DM+IR, n=20), and healthy controls (HC, n=30). mRNA levels of the cytokines in peripheral blood mononuclear cells (PBMCs) were quantified using qRT-PCR, and serum protein levels were assessed via ELISA.

Results: Significant upregulation of IL-6 mRNA in PBMCs was observed in the DM+IR and DM-IR groups compared to controls and the IR only group, while serum IL-6 protein was paradoxically lower in DM+IR compared to DM-IR. Both IL-10 mRNA and serum protein levels were elevated in the DM-IR group, suggesting a compensatory anti-inflammatory response, but were downregulated in the DM+IR group. IL-1β showed a similar pattern, with increased mRNA and serum protein in DM-IR and decreased serum protein in DM+IR.

Conclusion: The findings reveal distinct inflammatory cytokine profiles associated with IR and T2DM, highlighting discrepancies between mRNA and protein levels that suggest complex post-transcriptional and translational regulation. These results emphasize the necessity for careful interpretation of cytokine expression in the context of metabolic disorders.

Background & objective: Use of fine needle aspiration cytology (FNAC) in the diagnosis of salivary gland neoplasms is controversial due to the diverse morphologic patterns and overlapping features between benign and malignant lesions. The Milan system has been introduced to report salivary gland cytopathology. The present study aimed to reclassify salivary gland lesions according to the Milan system for reporting salivary gland cytopathology (MSRSGC) to determine the risk of malignancy (ROM) and to estimate the diagnostic accuracy of the Milan system.

Methods: In this retrospective cohort study, 136 salivary gland fine needle aspiration cytology samples taken from patients referred to Imam Khomeini and Amir-Aalam Hospital, Tehran, Iran, from 2016 to 2021, were retrieved along with the histopathological follow-up. Cytology smears were reviewed and reclassified based on MSRSGC. In addition, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were calculated.

Results: ROM for each category was 26.7% for non-diagnostic, 12.5% for non-neoplastic, 40% for atypia of undetermined significance (AUS), 0 for benign neoplasm, 0 for salivary gland neoplasm with uncertain malignant potential (SUMP), 100% for suspicious for malignancy, and 100% for malignant group. Sensitivity, specificity, PPV, and NPV in differentiating benign from malignant neoplasms based on MSRSGC were 75.9%, 100%, 100%, and 93.8%, respectively. Diagnostic accuracy was calculated as 94.8%.

Conclusion: MSRSGC may be associated with a high accuracy in differentiation of benign from malignant salivary gland neoplasms, indicating its potential value as an effective classification system for reporting salivary gland cytology. The ROM for cytological categories except SUMP can be almost similar to that suggested by MSRSGC.