Extracellular vesicle proteins as breast cancer biomarkers: Mass spectrometry-based analysis.

Extracellular vesicles (EVs) are membrane-surrounded vesicles released by various cell types into the extracellular microenvironment. Although EVs vary in size, biological function, and components, their importance in cancer progression and the potential use of EV molecular species to serve as novel cancer biomarkers have become increasingly evident. Cancer cells actively release EVs into surrounding tissues, which play vital roles in cancer progression and metastasis, including invasion and immune modulation. EVs released by cancer cells are usually chosen as a gateway in the search for biomarkers for cancer. In this review, we mainly focused on molecular profiling of EV protein constituents from breast cancer, emphasizing mass spectrometry (MS)-based proteomic approaches. To further investigate the potential use of EVs as a source of breast cancer biomarkers, we have discussed the use of these proteins as predictive marker candidates. Besides, we have also summarized the key characteristics of EVs as potential therapeutic targets in breast cancer and provided significant information on their implications in breast cancer development and progression. Information provided in this review may help understand the recent progress in understanding EV biology and their potential role as new noninvasive biomarkers as well as emerging therapeutic opportunities and associated challenges.

The efficacy and assessment value of the level of thyroglobulin wash-out after fine-needle aspiration cytodiagnosis in the evaluation of lymph node metastasis in papillary thyroid carcinoma.

OBJECTIVE: The purpose of this study was to evaluate the efficacy and clinical value of US, FNAC,FNA-Tg and FNAC + FNA-Tg, as well as the cutoff values of FNA-Tg to evaluate LN metastasis. METHODS: We analyzed the diagnostic value of different US signs, the efficiency of US, FNAC, FNA-Tg and FNAC + FNA-Tg among the LN- and LN + groups, and the cutoff value of FNA-Tg to evaluate LN metastasis. We punctured LNs multiple times and measured the levels of FNA-Tg. Furthermore, the LNs were marked with immunohistochemical Tg and LCA to distinguish the presence of Tg in the para-cancerous tissue of the LNs. RESULTS: The s-Tg and FNA-Tg of the LN + group were higher than those of the LN- group (P = 0.018, ≤ 0.001). The LN + group had more abnormal US signs than the LN- group. The cutoff value of FNA-Tg was 3.2 ng/mL. US had a high sensitivity (92.42), but the specificity was not satisfactory (55.1). FNA-Tg had a higher sensitivity (92.42 vs. 89.39), specificity (100 vs. 93.88), and accuracy (92.42 vs. 83.27) than FNAC. However, the sensitivity of FNAC + FNA-Tg increased further, while the specificity and accuracy decreased slightly. The presence of Tg in the normal lymphocytes adjacent to the cancer was confirmed. CONCLUSION: Ultrasonography provides a noninvasive, dynamic, multidimensional assessment of LNs. With a cutoff value of 3.2 ng/mL, FNA-Tg has higher accuracy and a lower false-negative rate than various single diagnoses. However, FNAC combined with FNA-Tg does not cause additional pain to patients and offers a higher diagnostic efficacy and clinical value.

Heterogeneity in PD-L1 expression between primary and metastatic lymph nodes: a predictor of EGFR-TKI therapy response in non-small cell lung cancer.

BACKGROUND: There is inconclusive evidence to suggest that the expression of programmed cell death ligand 1 (PD-L1) is a putative predictor of response to EGFR-TKI therapy in advanced EGFR-mutant non-small cell lung cancer (NSCLC). We evaluated the heterogeneity in PD-L1 expression in the primary lung site and metastatic lymph nodes to analyze the association between PD-L1 expression and response for patients treated with EGFR-TKI. METHODS: This study reviewed 184 advanced NSCLC patients with EGFR mutations who received first-generation EGFR-TKI as first-line treatment from 2020 to 2021 at Shanghai Chest Hospital. The patients were divided into the primary lung site group (n = 100) and the metastatic lymph nodes group (n = 84) according to the biopsy site. The patients in each group were divided into TPS < 1%, TPS 1-49%, and TPS ≥ 50% groups according to PD-L1 expression. RESULTS: The median PFS was 7 (95% CI: 5.7-8.3) months, and the median OS was 26 (95% CI: 23.5-28.5) months for all patients. No correlation existed between PFS or OS and PD-L1 expression. The median PFS in the primary lung site group was 11 months (95% CI: 9.6-12.4) in the TPS < 1% group, 8 months (95% CI: 6.6-9.4) in TPS 1-49% group, and 4 months (95% CI: 3.2-4.8) in TPS ≥ 50% group, with statistically significant differences (p = 0.000). The median OS of the TPS < 1% group and TPS ≥ 50% group showed a statistically significant difference (p = 0.008) in the primary lung site group. In contrast, PD-L1 expression in the lymph nodes of EGFR-mutant patients was unrelated to PFS or OS after EGFR-TKI therapy. CONCLUSION: PD-L1 expression from the primary lung site might predict clinical benefit from EGFR-TKI, whereas PD-L1 from metastatic lymph nodes did not. TRIAL REGISTRATION: This retrospective study was approved by the Ethics Committee of Shanghai Chest Hospital (ID: IS23060) and performed following the Helsinki Declaration of 1964 (revised 2008).

Diagnostic, predictive and prognostic molecular biomarkers in clear cell renal cell carcinoma: A retrospective study.

Clear cell renal cell carcinoma (ccRCC) is a common and aggressive subtype of kidney cancer. Many patients are diagnosed at advanced stages, making early detection crucial. Unfortunately, there are currently no noninvasive tests for ccRCC, emphasizing the need for new biomarkers. Additionally, ccRCC often develops resistance to treatments like radiotherapy and chemotherapy. Identifying biomarkers that predict treatment outcomes is vital for personalized care. The integration of artificial intelligence (AI), multi-omics analysis, and computational biology holds promise in bolstering detection precision and resilience, opening avenues for future investigations. The amalgamation of radiogenomics and biomaterial-basedimmunomodulation signifies a revolutionary breakthrough in diagnostic medicine. This review summarizes existing literature and highlights emerging biomarkers that enhance diagnostic, predictive, and prognostic capabilities for ccRCC, setting the stage for future clinical research.

Genomic Profiling of Rare Undifferentiated Sarcomatoid Subtypes of Pancreatic Carcinomas: In Search of Therapeutic Targets.

PURPOSE: The highly aggressive undifferentiated sarcomatoid carcinoma (USC) subtype of pancreatic ductal adenocarcinoma (PDAC) remains poorly characterized because of its rarity. Previous case reports suggest that immune checkpoint inhibitors could be a promising treatment strategy, but the prevalence of established predictive biomarkers of response is largely unknown. The objective of this study was to leverage comprehensive genomic profiling of USC PDAC tumors to determine the prevalence of biomarkers associated with potential response to targeted therapies. METHODS: USC tumors (n = 20) underwent central pathology review by a board-certified gastrointestinal pathologist to confirm the diagnosis. These samples were compared with non-USC PDAC tumors (N = 5,562). Retrospective analysis of DNA and RNA next-generation sequencing data was performed. RESULTS: USC PDACs were more frequently PD-L1+ by immunohistochemistry than non-USC PDAC (63% v 16%, respectively, P < .001). Furthermore, USC PDAC had an increase in neutrophils (8.99% v 5.55%, P = .005) and dendritic cells (1.08% v 0.00%, q = 0.022) and an increased expression of PDCD1LG2 (4.6% v 1.3%, q = 0.001), PDCD1 (2.0% v 0.8%, q = 0.060), and HAVCR2 (45.9% v 21.7%, q = 0.107) than non-USC PDAC. Similar to non-USC PDAC, KRAS was the most commonly mutated gene (86% v 90%, respectively, P = 1). CONCLUSION: To our knowledge, this work represents the largest molecular analysis of USC tumors to date and showed an increased expression of immune checkpoint genes in USC tumors. These findings provide evidence for further investigation into immune checkpoint inhibitors in USC tumors.

Evolving Diagnostic Approach of Pulmonary Salivary Gland-type Tumors.

Pulmonary salivary gland-type, although bear resemblance to their salivary gland counterparts, present a diagnostic challenge due to their rarity. Clinical features overlap with lung carcinoma; however, management strategies and outcomes are distinct. Onus falls on the pathologist to avoid misinterpretation of small biopsies especially in young, nonsmokers with slow growing or circumscribed endobronchial growths. A combination of cytokeratin, myoepithelial immunohistochemical markers, and identification of signature molecular alteration is invaluable in differentiation from lung cancers and subtyping the pulmonary salivary gland-type tumor.

Considerations for using potential surrogate endpoints in cancer screening trials.

The requirement of large-scale expensive cancer screening trials spanning decades creates considerable barriers to the development, commercialisation, and implementation of novel screening tests. One way to address these problems is to use surrogate endpoints for the ultimate endpoint of interest, cancer mortality, at an earlier timepoint. This Review aims to highlight the issues underlying the choice and use of surrogate endpoints for cancer screening trials, to propose criteria for when and how we might use such endpoints, and to suggest possible candidates. We present the current landscape and challenges, and discuss lessons and shortcomings from the therapeutic trial setting. It is hugely challenging to validate a surrogate endpoint, even with carefully designed clinical studies. Nevertheless, we consider whether there are candidates that might satisfy the requirements defined by research and regulatory bodies.

Identifying malignant mesothelioma by a pathological survey using the São Paulo state hospital cancer registry, Brazil.

OBJECTIVE: To review the pathological diagnosis of possible cases and/or hidden cases of malignant mesothelioma (MM) between 2000 and 2012 using the Hospital-Based Cancer Registry database in the state of São Paulo, Brazil. METHODS: Possible cases were retrieved by assessing the database. Inclusion criteria were being older than 30 years of age and having ICD-O-3 topography and morphology codes related to MM. A board of expert pathologists reviewed the pathology reports and requested paraffin blocks in cases that demanded revision. After staining with calretinin, D2-40, WT-1 (as positive MM markers) and Ber-EP4 and MOC31 (as negative MM markers), cases were divided and studied independently by a pair of pathologists to confirm or discard the diagnosis of MM. RESULTS: Our sample comprised 482 cases from 25 hospitals, and 130 needed further histological revision. We received 73 paraffin blocks with adequate material. After board analysis, there were 9 cases with a definitive diagnosis of MM, improving the diagnostic rate in 12%. Two cases of previously diagnosed MM were discarded by review. CONCLUSIONS: Our results confirm that part of MM underdiagnosis and underreporting in Brazil is due to incomplete or mistaken pathological diagnosis.

Functional hemodynamic imaging markers for the prediction of pathological outcomes in breast cancer patients treated with neoadjuvant chemotherapy.

Significance: Achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) is a significant predictor of increased likelihood of survival in breast cancer patients. Early prediction of pCR is of high clinical value as it could allow personalized adjustment of treatment regimens in non-responding patients for improved outcomes. Aim: We aim to assess the association between hemoglobin-based functional imaging biomarkers derived from diffuse optical tomography (DOT) and the pathological outcome represented by pCR at different timepoints along the course of NACT. Approach: Twenty-two breast cancer patients undergoing NACT were enrolled in a multimodal DOT and X-ray digital breast tomosynthesis (DBT) imaging study in which their breasts were imaged at different compression levels. Logistic regressions were used to study the associations between DOT-derived imaging markers evaluated after the first and second cycles of chemotherapy, respectively, with pCR status determined after the conclusion of NACT at the time of surgery. Receiver operating characteristic curve analysis was also used to explore the predictive performance of selected DOT-derived markers. Results: Normalized tumor HbT under half compression was significantly lower in the pCR group compared to the non-pCR group after two chemotherapy cycles (p=0.042). In addition, the change in normalized tumor StO2 upon reducing compression from full to half mammographic force was identified as another potential indicator of pCR at an earlier time point, i.e., after the first chemo cycle (p=0.038). Exploratory predictive assessments showed that AUCs using DOT-derived functional imaging markers as predictors reach as high as 0.75 and 0.71, respectively, after the first and second chemo cycle, compared to AUCs of 0.50 and 0.53 using changes in tumor size measured on DBT and MRI. Conclusions: These findings suggest that breast DOT could be used to assist response assessment in women undergoing NACT, a critical but unmet clinical need, and potentially enable personalized adjustments of treatment regimens.

Recent advances in the applications of DNA frameworks in liquid biopsy: A review.

Cancer is one of the serious threats to public life and health. Early diagnosis, real-time monitoring, and individualized treatment are the keys to improve the survival rate and prolong the survival time of cancer patients. Liquid biopsy is a potential technique for cancer early diagnosis due to its non-invasive and continuous monitoring properties. However, most current liquid biopsy techniques lack the ability to detect cancers at the early stage. Therefore, effective detection of a variety of cancers is expected through the combination of various techniques. Recently, DNA frameworks with tailorable functionality and precise addressability have attracted wide spread attention in biomedical applications, especially in detecting cancer biomarkers such as circulating tumor cells (CTCs), exosomes and circulating tumor nucleic acid (ctNA). Encouragingly, DNA frameworks perform outstanding in detecting these cancer markers, but also face some challenges and opportunities. In this review, we first briefly introduced the development of DNA frameworks and its typical structural characteristics and advantages. Then, we mainly focus on the recent progress of DNA frameworks in detecting commonly used cancer markers in liquid-biopsy. We summarize the advantages and applications of DNA frameworks for detecting CTCs, exosomes and ctNA. Furthermore, we provide an outlook on the possible opportunities and challenges for exploiting the structural advantages of DNA frameworks in the field of cancer diagnosis. Finally, we envision the marriage of DNA frameworks with other emerging materials and technologies to develop the next generation of disease diagnostic biosensors.

Correlation of Ki-67 proliferative index with oncotype DX recurrence score in hormone receptor-positive, human epidermal growth factor receptor 2-negative early breast cancer with low-burden axillary nodal disease - a review of 137 cases.

The use of chemotherapy in breast cancer management has significantly contributed to the decrease in its mortality. Currently, the prognosis is determined by molecular biomarkers, such as oestrogen receptors, and human epidermal growth factor receptor 2. However, the increasing use of advanced molecular technologies, including oncotype DX recurrence score (ODX-RS), has provided the ability to estimate the risk of recurrence. Research has demonstrated that the ODX-RS helps to predict recurrence risk and the potential benefit of chemotherapy in breast cancer. As a result, it can assist clinicians in making decisions regarding using the chemotherapy. The goal of work is to explore the correlation between the ODX-RS and Ki-67 proliferative index (Ki-67-PI). This study included 137 patients with oestrogen positive, human epidermal growth factor receptor 2-negative early breast cancer, and had non- or early axillary disease. Patients with low Ki-67-PI were as follows: low ODX-RS in 17%, intermediate ODX-RS in 80%, and high ODX-RS in 2%. In the high Ki-67-PI group: low ODX-RS in 12%, intermediate ODX-RS in 48%, and high ODX-RS in 40%. In conclusion, the results show no significant correlation between the ODX-RS and Ki-67-PI (r = 0.511, p-value < 0.9).

Expression of p16 protein in breast cancer.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Potential application of body fluids autofluorescence in the non-invasive diagnosis of endometrial cancer.

BACKGROUND: Endometrial carcinoma (EC) is the most common cancer of the female reproductive tract in developed countries. The prognosis and 5-year survival rates are closely tied to the stage diagnosis. Current routine diagnostic methods of EC are either lacking specificity or are uncomfortable, invasive and painful for the patient. As of now, the gold diagnostic standard is endometrial biopsy. Early and non-invasive diagnosis of EC requires the identification of new biomarkers of disease and a screening test applicable to routine laboratory diagnostics. The application of untargeted metabolomics combined with artificial intelligence and biostatistics tools has the potential to qualitatively and quantitatively represent the metabolome, but its introduction into routine diagnostics is currently unrealistic due to the financial, time and interpretation challenges. Fluorescence spectral analysis of body fluids utilizes autofluorescence of certain metabolites to define the composition of the metabolome under physiological conditions. PURPOSE: This review highlights the potential of fluorescence spectroscopy in the early detection of EC. Data obtained by three-dimensional fluorescence spectroscopy define the quantitative and qualitative composition of the complex fluorescent metabolome and are useful for identifying biochemical metabolic changes associated with endometrial carcinogenesis. Autofluorescence of biological fluids has the prospect of providing new molecular markers of EC. By integrating machine learning and artificial intelligence algorithms in the data analysis of the fluorescent metabolome, this technique has great potential to be implemented in routine laboratory diagnostics.

CD3, CD8, IFN-γ, tumor and stroma inflammatory cells as prognostic indicators for surgically resected SCLC: evidences from a 10-year retrospective study and immunohistochemical analysis.

Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.

Identifying potential breath biomarkers for early diagnosis of papillary thyroid cancer based on solid-phase microextraction gas chromatography-high resolution mass spectrometry with metabolomics.

INTRODUCTION: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. OBJECTIVES: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). METHODS: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. RESULTS: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method CONCLUSION: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers.

Immune Checkpoint Inhibitors in Esophageal Carcinoma: Assessment of Efficacy Predictors of Response in Clinical Trials.

Esophageal carcinoma (EC) is among the most common causes of cancer-related deaths worldwide. Even with the improvement of multidisciplinary treatment modalities, advanced unresectable EC patients had limited systemic therapeutic options for an extended period. Recently, immune checkpoint inhibitors (ICIs) have been introduced to advanced EC management in both first-line and second-line options, as well as in postoperative settings in resectable EC after preoperative chemoradiation. Herein, the authors present a comprehensive review of clinical trials on administering ICIs in EC patients while discussing reported clinical, molecular, and immune biomarkers and their predictive value for treatment efficacy.

Gastric cancer immune microenvironment score predicts neoadjuvant chemotherapy efficacy and prognosis.

The efficacy of neoadjuvant chemotherapy (NACT) in patients with advanced gastric cancer (GC) varies greatly. Thus, we aimed to verify the predictive value of tumor-infiltrating immune cells (TIICs) on the treatment response to NACT and the prognosis of patients with advanced GC, and to explore the impact of NACT on the tumor immune microenvironment (TIME). Paired tumor tissues (pre- and post-NACT) from patients with advanced GC were collected for this study. TIICs were assessed using immunohistochemistry staining and analyzed using logistic regression to establish an immune microenvironment score for GC (ISGC score) and predict NACT efficacy. Kaplan-Meier curves were used to evaluate the survival outcome of patients. The results showed that TIME was dramatically heterogeneous between NACT response and nonresponse patients. In the validation cohort, the ISGC score demonstrated good predictive performance for treatment response to NACT. Moreover, high ISGC indicated better long-term survival in patients with advanced GC. Furthermore, tumor-infiltrated T cells (CD3+ and CD8+) and CD11c+ macrophages were significantly increased in the response group, while CD163+ macrophages and FOXP3+ Treg cells were decreased after NACT. However, opposite results were exhibited in the nonresponse group. Finally, we found that the percentage of programmed cell death ligand 1 (PD-L1)-positive tumors was 31% (32/104) pre-NACT and 49% (51/104) post-NACT, and almost all patients with elevated PD-L1 were in the NACT response group. The ISGC model accurately predicted NACT efficacy and classified patients with GC into different survival groups. NACT regulates the TIME in GC, which may provide strategies for personalized immunotherapy.

Diagnostic and prognostic assessments of adrenocortical carcinomas by pathological features, immunohistochemical markers and reticular histochemistry staining.

BACKGROUND: Current diagnostic criteria of adrenocortical neoplasms are mostly based on morphology. The utility of immunohistochemistry (IHC) and histochemistry is limited. MATERIALS AND METHODS: To evaluate the diagnostic and prognostic utility of clinicopathological features, morphology, ancillary biomarkers, and reticular histochemistry in adrenocortical neoplasms. We examined 28 adrenocortical carcinomas (ACCs) and 50 adrenocortical adenomas (ACAs) obtained from pathology archives. Clinical data were retrieved from medical records. Two pathologists independently assessed hematoxylin and eosin-stained slides, employing modified Weiss criteria for all tumors and Lin-Weiss-Bisceglia criteria for oncocytic variants. Immunohistochemical markers (Calretinin, alpha-inhibin, MelanA, SF-1, Ki-67, PHH3, IGF-2, ß-catenin, P53, CYP11B1, CYP11B2, MLH1, MSH2, MSH6, PMS2, EPCAM) and Gomori's Silver histochemistry were applied. Statistical analysis utilized SPSS Statistics 26. RESULTS: ACCs exhibited larger tumor sizes (P<0.001) and symptomatic presentations (P = 0.031) compared to ACAs. Parameters of modified Weiss criteria and angioinvasion demonstrated diagnostic value for ACCs. Six immunohistochemical antibodies((MelanA, Ki-67, IGF-2, ß-catenin, P53 and CYP11B1) and reticulin framework alterations showed diagnostic value. Notably, Ki-67 and reticulin staining were most recommended. Evident reticulin staining was frequently present in ACCs (P<0.001). Ki-67 was significantly higher in ACCs (P<0.001). Twenty-one conventional and seven oncocytic entities showed different necrosis frequencies. Symptoms and Ki-67 index ≥ 30% were prognostic for ACCs, correlating with shorter survival. CONCLUSIONS: This study emphasizes the diagnostic value of reticulin framework alterations and a high Ki-67 index. Markers such as CYP11B1, IGF2, P53, ß-catenin and MelanA also contribute to the diagnosis of ACCs. Symptoms and Ki-67 index ≥ 30% predict shorter survival. These findings encourges the use of ancillary markers such as reticulin histochemistry and Ki-67 in the workup of evaluations of adrenocortical neoplasms.

Diagnostic and prognostic performances of GALAD score in staging and 1-year mortality of hepatocellular carcinoma: A prospective study.

BACKGROUND: The GALAD score has improved early hepatocellular carcinoma (HCC) detection rate. The role of the GALAD score in staging and predicting tumor characteristics or clinical outcome of HCC remains of particular interest. AIM: To determine the diagnostic/prognostic performances of the GALAD score at various phases of initial diagnosis, tumor features, and 1-year mortality of HCC and compare the performance of the GALAD score with those of other serum biomarkers. METHODS: This prospective, diagnostic/prognostic study was conducted among patients with newly diagnosed HCC at the liver center of Vajira Hospital. Eligible patients had HCC staging allocation using the Barcelona Clinic Liver Cancer (BCLC) categorization. Demographics, HCC etiology, and HCC features were recorded. Biomarkers and the GALAD score were obtained at baseline. The performance of the GALAD score and biomarkers were prospectively assessed. RESULTS: Exactly 115 individuals were diagnosed with HCC. The GALAD score increased with disease severity. Between BCLC-0/A and BCLC-B/C/D, the GALAD score predicted HCC staging with an area under the curve (AUC) of 0.868 (95%CI: 0.80-0.93). For identifying the curative HCC, the AUC of GALAD score was significantly higher than that of Alpha-fetoprotein (AFP) (0.753) and Lens culinaris agglutinin-reactive fraction of AFP-L3 (0.706), and as good as that of Protein induced by vitamin K absence-II (PIVKA-II) (0.897). For detecting aggressive features, the GALAD score gave an AUC of 0.839 (95%CI: 0.75-0.92) and significantly outperformed compared to that of AFP (0.761) and AFP-L3 (0.697), with a trend of superiority to that of PIVKA-II (0.772). The performance to predict 1-year mortality of GALAD score (AUC: 0.711, 95%CI: 0.60-0.82) was better than that of AFP (0.541) and as good as that of PIVKA-II (0.736). The optimal cutoff value of GALAD score was ≥ 6.83, with a specificity of 72.63% for exhibiting substantial reduction in the 1-year mortality. CONCLUSION: The GALAD model can diagnose HCC at the curative stage, including the characteristic of advanced disease, more than that by AFP and AFP-L3, but not PIVKA-II. The GALAD score can be used to predict the 1-year mortality of HCC.

Pediatric high grade gliomas: A comprehensive histopathological, immunohistochemical and molecular integrated approach in routine practice.

Pediatric high grade gliomas have undergone remarkable changes in recent time with discovery of new molecular pathways. They have been added separately in current WHO 2021 blue book. All the entities show characteristic morphology and immunohistochemistry. Methylation data correctly identifies these entities into particular group of clusters. The pediatric group high grade glioma comprises- Diffuse midline glioma, H3K27-altered; Diffuse hemispheric glioma, H3G34-mutant; Diffuse pediatric-type high-grade glioma, H3-wild type & IDH-wild type; Infant hemispheric glioma and Epithelioid glioblastoma/Grade 3 pleomorphic xanthoastrocytoma and very rare IDH-mutant astrocytoma. However it is not always feasible to perform these molecular tests where cost-effective diagnosis is a major concern. Here we discuss the major entities with their characteristic histopathology, immunohistochemistry and molecular findings that may help to reach to suggest the diagnosis and help the clinician for appropriate treatment strategies. We have also made a simple algorithmic flow chart integrated with histopathology, immunohistochemistry and molecular characteristics for better understanding.