Applied Immunohistochemistry & Molecular Morphology最新文献

Colorectal cancer (CRC) is one of the most common digestive tract tumors in humans. At present, many scholars believe that the primary site of the tumor has a direct and profound impact on its curative effect. There are significant differences in the expression of many genes, tumor microenvironment, and prognosis between the left and right colon. However, there is a lack of detailed studies on whether the differentially expressed genes in the left and right colon significantly impact the prognosis of patients with CRC. Troponin T1 ( TNNT1 ) is an important gene that affects the prognosis difference between left and right colon cancer screening from "The Cancer Genome Atlas" database. By analyzing the differential gene expression data and clinical data of the left and right hemicolons in the database, the online prognostic database was used to screen the key molecules that significantly affect the tumor immune microenvironment and patient prognosis and to predict their functions and pathways. Quantitative reverse transcription-polymerase chain reaction was used to verify the expression difference of TNNT1 in CRC cell lines SW480 and HCT116, and normal human colorectal epithelial cell line FHC. The relationship between TNNT1 expression in 88 pairs of CRC samples and clinical information and pathologic parameters of patients with CRC was analyzed to judge the impact of TNNT1 expression on patient survival. Database analysis showed that TNNT1 was significantly overexpressed in CRC, and TNNT1 was one of the main differential genes between left colon cancer (LCC) and right colon cancer (RCC). The expression of TNNT1 was significantly increased in RCC, which could lead to poor prognosis of patients. Quantitative reverse transcription-polymerase chain reaction indicated that the expression of TNNT1 was significantly up-regulated in CRC cell lines SW480 and HCT116. Eighty-eight immunohistochemistry (IHC) of CRC tissues and adjacent tissues suggested that the expression of TNNT1 in CRC was significantly higher than that in normal adjacent tissues. By analyzing the clinical information and pathologic indicators matched with these clinical samples, we found that high TNNT1 expression in the primary tumor location (right colon) and high N stage (N2, N3) were unfavorable factors affecting the prognosis of patients with CRC. Multivariate Cox regression analysis suggested that high expression of TNNT1 may be an independent risk factor for the prognosis of patients with CRC. As one of the main differential genes between LCC and RCC, TNNT1 is representative to some extent. Its high expression may be one of the reasons why the prognosis of patients with RCC is worse than that of patients with LCC.

Uterine spindle cell lesions share a dilemmatic overlapped features that needed to be addressed by the pathologist to reach a conclusive accurate diagnosis for its prognostic value and different management decisions. Usage of combined IHC panel can be an aiding guiding tool in this context. The aim of this study is to evaluate the diagnostic value of combined BCOR, Cyclin D1, and CD10 IHC panel in differentiating endometrial stromal sarcoma from other uterine spindle cell lesions. This study included 60 cases categorized into endometrial stromal sarcoma group (ESS) (12 cases high-grade endometrial stromal sarcoma [HGESS] and 18 cases low-grade endometrial stromal sarcoma [LGESS]), malignant uterine spindle cell lesions group (5 cases adenosarcoma [AS], 6 cases leiomyosarcoma [LS], 4 cases carcinosarcoma [CS]), and benign uterine lesions group (5 cases endometrial stromal nodule [ESN], 5 cases leiomyoma, and 5 cases adenomyosis). IHC staining procedure and evaluation for BCOR, Cyclin D1, and CD10 was performed on all studied cases. BCOR IHC staining was positive in all HGESS (12/12) of ESS group cases, with diffuse pattern in 75% of cases. BCOR-diffuse staining pattern was not recorded in any of LGESS (0/18), malignant mesenchymal lesions group (0/15), and also benign lesions group (0/15). Cyclin D1 positivity was observed only in HGESS cases, in parallel with positive-BCOR expression. On the contrary, CD10 was negatively expressed in all HGESS and positive in all LGESS, ESN, and adenomyosis cases. A specificity of 100% and sensitivity of 75% were recorded in differentiating HGESS from malignant mesenchymal lesions (including LMS, AS, and CS) and also HGESS from LGESS when using the combined panel BCOR +ve D /Cyclin D1 +ve / CD10 -ve , considering only the BCOR-diffuse staining pattern. In conclusion, BCOR +ve D /Cyclin D1 +ve /CD10 -ve as a combined panel is 100% specific and with lesser sensitivity in diagnosing HGESS as well as differentiating it from LGESS and other malignant uterine spindle cell lesions.

Introduction: Multiplex polymerase chain reaction (PCR) and next-generation sequencing (NGS) can both be used to identify a neoplastic clonotype by targeting CDR3 and assessing rearrangements in IgH, IgK, IgL, TCR-β, and TCR-gamma loci. The clonotypic sequence can be robustly used to track minimal residual disease (MRD). The ability to track MRD by NGS in mixed phenotype acute leukemia (MPAL) is unknown and warrants investigation.

Methods: Institutional Review Board (IRB) approval was obtained. Central Moffitt Cancer Center (MCC) database was searched to locate any patients with MPAL from over 600,000 entries. Patient charts were manually curated to identify those with clonoSEQ data, and clinical data was procured from the electronic medical record (EMR).

Results: Twenty-nine patients with MPAL were identified. Only 2 patients with clonoSEQ testing were found. Both demonstrated a B/myeloid phenotype, and both were bilineal. NGS (clonoSEQ) identified 4 dominant (IGH) (patient A; 8/2019) and 2 dominant sequences (patient B; 10/2019), respectively. In both patients, clonoSEQ testing successfully tracked minimal residual disease and mirrored clinical disease burden.

Conclusions: This report is the first to confirm the utility of NGS-based MRD tracking in patients with MPAL and shows increased sensitivity of NGS over MRD flow cytometry.

There is a limited amount of data on the role of programmed cell death ligand (PD-L) -1 and PD-L2 in salivary gland carcinomas. We aimed to evaluate the prognostic value of PD-L1 and PD-L2 expressions, which are closely related to immune mechanisms, with respect to salivary gland tumor types and stages. Data from patients with salivary gland masses surgically removed between 2006 and 2021, diagnosed with a malignant salivary gland neoplasm, were retrospectively analyzed. Immunoreactivity for PD-L1 and PD-L2 was performed on resection materials. The mean age of 90 patients was 52.1±18.8 and 46.7% were male. Overall, 55.6% of patients were diagnosed with adenoid cystic carcinoma (ACC), 23.3% with mucoepidermoid carcinoma (MEC), 16.7% with acinic cell carcinoma (AciCC), 3.3% with ductal carcinoma (DC), and 1 patient with pleomorphic adenoma ex carcinoma (PA-ex-CA). In all, 52% of ACC, 12% of AciCC, 24% of MEC, and 12% of DC cases were at stage IV. The tumor diameter, frequencies of lymphovascular invasion, metastasis, positive surgical margin, recurrence, and mortality rates of patients at stages III and IV were significantly larger than those at stages I and II ( P <0.05). The percentages of tumor cell score (TCS) and immune cell score (ICS) for PD-L1 were significantly higher among patients with MEC compared with those with other types of tumors ( P =0.0011). However, the percentages of combined score (CS) for PD-L1 and tumor cell score for PD-L2 were comparable among tumor types ( P >0.05). No significant difference was found in these scores for PD-L1 between tumor stages ( P >0.05), but for PD-L2, all patients at stage I had TCS <1% for PD-L2, while all patients at stages II and III, and 92% of patients at stage IV had TCS ≥1% ( P <0.0001). High expression of PD-L1 was mostly observed in MEC cases ( P =0.0016), while all patients with AciCC had a low PD-L1 expression level ( P =0.0206). The mean tumor diameter, rate of lymphovascular invasion, perineural invasion, metastasis, positive surgical margin, recurrence, type of treatment, mortality, and TILs ratio did not differ significantly according to PD-L1 expression level ( P >0.05). The percentage of tumor-infiltrating lymphocytes was comparable among negative and positive PD-L1 scores according to both 1% and 5% threshold values ( P >0.05). High PD-L1 expression is rare in AciCC, while PD-L1 expression is high in MEC. Our findings underline the importance of future screening for PD-L1 and PD-L2 before patients undergoing immunotherapies in all salivary gland tumors.

Objectives: To find predictive biomarkers for recurrence and progression of meningioma.

Background: Despite great advances in meningioma treatment, the prognosis remained unfavorable due to the high recurrence rate.

Methods: In this study, we evaluated the immunohistochemical expression of FOXM1, MMP-9, and Ki67 in 50 cases of intracranial meningioma to detect its potential role in meningioma progression, recurrence, and patients' survival.

Results: Strong FOXM1 expression was detected in 20% of the cases and was significantly associated with meningioma grade ( P = 0.002) and peritumoral brain edema (PTBE; P <0.001). Strong MMP-9 expression was noted in 32% of the cases and was significantly associated with meningioma grade and PTBE ( P <0.001, P <0.001, respectively). High Ki67 was noted in 50% and significantly associated with tumor grade and PTBE ( P <0.001, P = 0.002, respectively). The follow-up period revealed that meningiomas with strong FOXM1, strong MMP-9, and high Ki67 expression were associated with tumor recurrence, shorter OS, and recurrence-free survival. Furthermore, up-regulation of FOXM1 and MMP-9 expression had a significant relation with poor clinical response to the therapy ( P = 0.010, P = 0. 001, respectively). However, high Ki67 cases were more sensitive to clinical therapy ( P = 0.005).

Conclusion: Strong FOXM1, strong MMP-9, and high Ki67 in meningiomas indicate highly aggressive tumors with a shortened survival rate, dismal outcome, and high risk of recurrence after the standard protocol of therapy.

The objective of this study was to analyze the expression and prognostic role of methylthioadenosine phosphorylase (MTAP) in mesothelioma. MTAP protein expression by immunohistochemistry was analyzed in 113 mesotheliomas (60 pleural and 53 peritoneal), consisting of 36 effusions and 77 surgical specimens. MTAP expression was fully lost in 38 tumors and partially lost in 8 tumors. Loss of expression was significantly more common in effusions compared with biopsies/surgical resection specimens (20/36 vs. 26/77; P =0.017), and in pleural compared with peritoneal mesotheliomas (35/60 vs. 11/53; P <0.001). MTAP performed less robustly than BAP1 in comparative analysis of 57 tumors previously analyzed for expression of the latter protein (46 vs. 25 cases with loss of expression). In survival analysis for 69 patients with partial clinical data, male gender was significantly associated with shorter overall survival (OS; P =0.042), whereas loss of MTAP was associated with a trend for shorter OS ( P =0.058), with no prognostic role for patient age ( P =0.379) or anatomic site ( P =0.381). The association between loss of MTAP and poor OS became significant when survival analysis was limited to patients with pleural mesothelioma ( P =0.018). In conclusion, loss of MTAP expression is more frequent in pleural compared with peritoneal mesothelioma and has limited diagnostic relevance at the latter anatomic site. More frequent loss in effusion specimens suggests a role for this marker in effusion cytology. MTAP loss in pleural mesothelioma is associated with poor survival.

Knowledge of the molecular pathways of pediatric high-grade gliomas is increasing. Gliomas with mismatch repair deficiency do not currently comprise a distinct group, but data on this topic have been accumulating in recent publications. Immunohistochemistry can effectively determine mismatch repair status, indirectly suggesting the microsatellite instability of the tumor. This study aimed to determine the number of mismatch repair-deficient pediatric high-grade gliomas in a tertiary institution and assess the relationship between the survival and mismatch repair status of the patients. It also aimed to assess the potential for further clinical studies including immunotherapy. Of 24 patients with high-grade gliomas, 3 deceased patients were mismatch repair-deficient. Mismatch repair deficiency was significantly associated with shorter survival ( P =0.004). Immunotherapy trials need to progress, and patients with mismatch repair-deficient pediatric high-grade gliomas are the most suitable candidates for such studies.

Programmed cell death receptor 1/Programmed cell death ligand 1 (PD-L1) checkpoint pathway is responsible for the control of immune cell responses. Immunotherapy using checkpoint inhibitors, such as anti-PD-L1 therapy, aids disease management and potentiates clinical outcomes. This study aimed to analyze the performance of the Leica Biosystems (LBS) USA FDA class I in vitro diagnostic monoclonal antibody (clone 73-10) to detect PD-L1 expression in breast, colorectal, and hepatocellular carcinomas compared with the class III FDA-approved PD-L1 detecting antibodies [SP263 (Ventana), 22C3 (Dako), and 28-8 (Dako)] using 208 unique tissue microarray-based cases for each tumor type. The interassay concordances between LBS 73-10 clone and other PD-L1 antibodies ranged from 0.59 to 0.95 Cohen kappa coefficient (K) and from 0.66 to 0.90 (K) for cutoff values of 1% and 50% tumor proportion score (TPS), respectively. The 73-10 clones showed inter-pathologist agreements ranging from 0.53 to 1.0 (K) and 0.34 to 0.94 (K) for cutoff values of 1% and 50% TPS, respectively. For the immune cell proportion score (IPS) using a cutoff of 1%, the Kappa coefficient of interassay concordances and inter-pathologist agreements ranged from 0.34 to 0.94. The 73-10 clone assay's sensitivity ranged from 78.3% to 100% (TPS ≥1%), 100% (TPS ≥50%), and 77.4% to 93.5% (IPS ≥1%), while its specificity was 97.9% to 100% (TPS ≥1%), 99.5% to 99.8% (TPS ≥50%), and 97.9% to 100% (IPS ≥1%). This exploratory evaluation of LBS 73-10 monoclonal antibody on a large set of breast, colorectal, and hepatocellular carcinomas showed the assay's technical performance is comparable to the FDA-approved companion/complementary diagnostics PD-L1 detection assays.

Xeroderma Pigmentosum (XP) is a genetic disorder characterized by photosensitivity, dyschromia, and high risk of skin cancer. From a clinical and histologic view, it can be difficult to diagnose cutaneous melanoma (CM) in XP patients and to define its resection margins. We aimed to study the role of PRAME (PReferentially Expressed Antigen in MElanoma) in differentiating intraepidermal CM from superficial atypical melanocytic proliferation of uncertain significance (SAMPUS) and evaluating the histological margins of CMs. We included XP patients. melanocitic and nonmelanocytic lesions with adjacent skin, and, as control groups, sun-damaged skin from non-XP individuals. Melanocytic lesions with a consensus diagnosis were grouped into CM, SAMPUS, or benign. The selected samples were PRAME-immunoshistochemically stained, and the ratio between immuno-positive cells/mm was recorded, according to Olds and colleagues for intraepidermal lesions. Lezcano and colleagues' method was used for intradermal lesions. Clinical data from XP patients were reviewed. All 9 patients were alive and well at the study closure, even those who developed melanoma metastases. Positive/diffuse PRAME expression was found in 29% (7/24) of intraepidermal CMs and 20% (1/5) SAMPUS samples. All 103 XP control samples and 24 adjacent lesions skin of non-XP patients were PRAME negative. This was a single-center and retrospective study, using a relatively small sample, limiting our conclusions. In XP patients' lesions, PRAME expression could help in the setting of challenging melanocytic tumors and surgical margins evaluation. It is also possible that the method can avoid overdiagnosis and, consequently, more aggressive treatment recommendation in unequivocal CM cases.

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.