Deep Learning-Based H-Score Quantification of Immunohistochemistry-Stained Images.

Immunohistochemistry (IHC) is a well-established and commonly used staining method for clinical diagnosis and biomedical research. In most IHC images, the target protein is conjugated with a specific antibody and stained using diaminobenzidine (DAB), resulting in a brown coloration, whereas hematoxylin serves as a blue counterstain for cell nuclei. The protein expression level is quantified through the H-score, calculated from DAB staining intensity within the target cell region. Traditionally, this process requires evaluation by 2 expert pathologists, which is both time consuming and subjective. To enhance the efficiency and accuracy of this process, we have developed an automatic algorithm for quantifying the H-score of IHC images. To characterize protein expression in specific cell regions, a deep learning model for region recognition was trained based on hematoxylin staining only, achieving pixel accuracy for each class ranging from 0.92 to 0.99. Within the desired area, the algorithm categorizes DAB intensity of each pixel as negative, weak, moderate, or strong staining and calculates the final H-score based on the percentage of each intensity category. Overall, this algorithm takes an IHC image as input and directly outputs the H-score within a few seconds, significantly enhancing the speed of IHC image analysis. This automated tool provides H-score quantification with precision and consistency comparable to experienced pathologists but at a significantly reduced cost during IHC diagnostic workups. It holds significant potential to advance biomedical research reliant on IHC staining for protein expression quantification.

HER3 is widely expressed across diverse subtypes of NSCLC in a retrospective analysis of archived tissue samples.

Aim: This noninterventional study (NCT05769764) aimed to characterize human epidermal growth factor receptor 3 (HER3) expression in non-small cell lung cancer (NSCLC) by patient, clinical or tumor characteristics.Methods: HER3 immunohistochemistry was performed in archival tissue samples from patients with advanced or metastatic NSCLC. Samples were scored for membrane percent positivity and intensity. Membrane H-scores were calculated.Results: Of 203 evaluable samples, HER3 expression was observed in 98.5%, including all histologies, genomic subtypes and regardless of prior systemic anticancer treatments. The median H-score was 140, and 70.4% had a HER3 intensity of 3+.Conclusion: HER3 is widely expressed in NSCLC, indicating that HER3-directed therapy may be broadly applicable across diverse subtypes of NSCLC.

[Box: see text].

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.

Serum soluble interleukin-2 receptor (sIL-2R) is an accurate biomarker for dengue-associated hemophagocytic lymphohistiocytosis syndrome diagnosed by Hscore.

OBJECTIVE: Hemophagocytic lymphohistiocytosis is a potentially fatal complication of severe dengue fever. Here we evaluated the serum soluble IL-2R levels as potential biomarker for identifying HLH in patients with dengue fever. METHODS: In this cross-sectional study conducted in a tertiary care center of a teaching hospital, subjects with dengue and fever of more than 5 days, leukopenia/thrombocytopenia and/or hepatosplenomegaly were studied. Data were collected to compare sIL-2R values and serum ferritin with Hscore and Histiocyte Society 2004 criteria. Relevant statistical methods were used. RESULTS: 80 subjects with severe dengue fever were analyzed with relevant investigations. Mean H score was 219.2 ± 17.6 in 18 dengue patients with HLH v/s 166.2 ± 11.2 in 62 patients without HLH (p = < 0.001). Serum ferritin (11,230.5 v/s 7853.5, p = 0.013) and sIL-2R (32,917.5 v/s 6210, p = < 0.001) were significantly higher in those patients with HLH. sIL-2R correlated very well with HScore (r = 0.98, p < 0.001) compared to ferritin (r = 0.51, p < 0.001) with an AUROC of 1.00 compared to 0.694 (95% CI 0.557-0.831) of serum ferritin for diagnosing HLH. A cut-off value of 10,345 pg/ml for sIL-2R had a sensitivity and specificity of 100% for HLH, whereas, a ferritin value of 8613 ng/ml had only 67% sensitivity and 55% specificity. CONCLUSION: sIL-2R could be a single most useful biomarker to differentiate dengue fever patients who are likely to progress to HLH, from those that are not. Full workup for HLH could be limited only to those patients with elevated sIL-2R, especially in resource limited settings.

Association between HER2 heterogeneity and clinical outcomes of HER2-positive gastric cancer patients treated with trastuzumab.

BACKGROUND: The GASTHER1 study showed that re-evaluation of HER2 status rescued 8% of HER2-positive gastric cancer (GC) patients with initially HER2-negative GC. Since rescued HER2 positivity represents HER2 heterogeneity, we aimed to investigate this in a larger cohort with longer follow-up duration. METHODS: Data of 153 HER2-positive advanced GC patients who received first-line trastuzumab-based chemotherapy were analyzed. Repeat endoscopic biopsy was performed in patients with initially HER2-negative GC. Survival outcomes were analyzed according to the immunohistochemistry (IHC) score (IHC 2+ /in situ hybridization [ISH] + vs IHC 3+), HER2 status (initially vs rescued HER2 positive), and H-score. RESULTS: IHC 2+ /ISH + patients showed worse progression-free survival (PFS) and overall survival (OS) than those with IHC 3+ (p < 0.05). Rescued HER2-positive patients showed worse PFS and OS than initially HER2-positive patients (p < 0.05). Although survival outcomes were comparable according to HER2 status in IHC 2+ /ISH + patients, initially HER2-positive patients showed more favorable PFS and OS than rescued HER2-positive patients (p < 0.05) among those with IHC 3+ . Among the subgroups determined by HER2 status and IHC score, the initially IHC 3+ subgroup had the highest H-score. The low H-score group (H-score ≤ 210) had significantly worse survival outcomes than the high H-score group (H-score > 210) (p < 0.05). An H-score of ≤ 210 was independently associated with shorter OS (HR = 1.54, 95% CI 1.02-2.31, p = 0.04). CONCLUSIONS: Rescued HER2-positive patients showed worse clinical outcomes than initially HER2-positive patients, especially those with IHC 3+ . This finding highlights the impact of HER2 heterogeneity, which can be quantified indirectly as an H-score.

Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Rate of secondary HLH and performance of H-score in patients with severe COVID-19.

BACKGROUND: Severe COVID-19 is thought to be caused by immune overdrive and cytokine storm. One of the cytokine storm syndromes frequently induced by infections is secondary hemophagocytic lymphohistiocytosis (HLH) which can be assessed using H-score. In this study, we aimed to evaluate the rate of patients with COVID-19 who meet HLH criteria based on H-score and the association of H-score with poor outcomes. METHODS: In a prospective cohort study of 19 patients with COVID-19 requiring ICU stay from March to May, 2020, we collected demographic and clinical data that focused on H-score's variables and COVID-19 outcomes. H-score ≥ 169 was used to determine the percentage of patients who met the HLH criteria. Mann-Whitney, Kruskal-Wallis, and Spearman rho tests and multiple regression analyses were carried out to evaluate the associated factors. The optimal H-score cut-off to predict poor COVID-19 outcome (need for intubation ± ECMO) was determined using receiver operating characteristic (ROC) analysis. RESULTS: In 669 patients with severe COVID-19 with a mean ± SD age of 50.3 ± 12.8 years, which comprised 95% men; 66% required intubation, 4% ECMO, and 16% died. Only 2% had an H-score ≥ 169. Patients with poor outcomes had a higher mean (SD) H-score than those without; intubation (96.0 [50.0] vs 75.0 [35.0], p < 0.01), ECMO (113.0 [25.0] vs 93.0 [50.0], p < 0.01) and death (98.0 [62.0] vs 93.0 [48.0], p < 0.01). Factors associated with H-score were diabetes (ß coeff = - 10.4, p < 0.01), abdominal pain (ß coeff = 19.1, p < 0.01), duration of COVID-19 symptoms (ß coeff = - 0.7, p = 0.049), and days before ICU admission (ß coeff = - 1.2, p = 0.01). H-score showed a fair ability to discriminate COVID-19 outcomes (AUC 0.61, 95% CI 0.54-0.67). An H-score of 85 was the optimal cut-off with a sensitivity 69% and 1-specificity 53%. CONCLUSION: Despite its association with severity in COVID-19, H-score's ability to predict poor outcomes was only fair, indicating differences in the cytokine storm faced in COVID-19 compared with that during secondary HLH.

A comprehensive analysis of adult patients with secondary hemophagocytic lymphohistiocytosis: a prospective cohort study.

Secondary hemophagocytic lymphohistiocytosis (HLH) is a rare but fatal condition with various underlying disorders in adult patients and is diagnosed based on the HLH-2004 criteria, which were established based on experience in pediatric patients. However, few studies have prospectively evaluated the treatment outcomes and diagnostic performance of HLH criteria in adult patients with secondary HLH. Thus, we performed a single-center, prospective cohort study of adult patients with suspected HLH, and we analyzed treatment outcomes of patients enrolled between 2017 and 2019 as an interim analysis ( ClinicalTrials.gov Identifier: NCT03117010). Of the 73 patients with suspected HLH, 70 patients completed the evaluation for ≥ 7 of the HLH-2004 criteria, and 55 patients were diagnosed with HLH (55/73, 75%). Although serum ferritin and fever had a sensitivity of more than 90%, both had exceptionally low specificity, whereas soluble CD25 had a sensitivity of more than 90% and specificity of 80%. Forty patients with malignancy-associated HLH had B cell (n = 19) or T- or NK-cell (n = 21) lymphoid malignancy, whereas 15 patients had non-malignant disorders. Non-malignancy-associated HLH had greater than 90% 1-year overall survival (OS) after diagnosis of HLH, whereas that for malignancy-associated HLH was less than 40%. In conclusion, our study showed promising treatment outcomes for patients enrolled in our prospective cohort study, and prospectively demonstrated the diagnostic performance of the HLH-2004 criteria in adult patients with suspected HLH. Given that lymphoma was the most common cause of HLH in adults, thorough evaluation for lymphoma should be performed in adults with suspected HLH.

Correlation of folate receptor alpha expression with clinicopathological parameters and outcome in triple negative breast cancer.

Folate receptor alpha (FRα) is a membrane-bound protein with a high affinity for folate, which is necessary for the biosynthesis of amino acids and nucleotide bases. It has been shown to be a potential prognostic and therapeutic target, primarily in lung and ovarian cancer, as well as in breast cancer. The aim of this study was to examine FRα expression in a cohort of patients with triple negative breast cancer (TNBC), in correlation with clinicopathological parameters and prognostic factors. By using polyclonal FRα antibody on archival paraffin blocks immunohistochemistry was performed. To evaluate the expression of FRα, H-score was used, which marks both the proportion of stained cells and the intensity of staining. Statistical analysis correlating FRα expression with clinicopathologic parameters and clinical outcome were performed. FRα was expressed in most of the patients (85%). Significant correlation of expression and histologic grade (Mann Whitney U test, P = 0,03) and type of tumor (P = 0,02), was found. It was noticed that with higher Ki-67 proliferation index values, H-score has lower values (r = -0,284, P = 0,006). Multivariant regression analysis (Cox regression, Stepwise method) showed H-score as a significant predictor for the risk of disease recurrence (OR = 1,005, P = 0,04). No correlation between FRα expression and overall survival (OS) and disease-free survival (DFS) was found. In conclusion, FRα is highly expressed in TNBC, and, given the correlation with clinicopathological parameters, subpopulation of patients could be identified that could be potential targets for new therapeutic perspectives in the treatment of this breast cancer subtype.

Increased C4d and Bb immunoreactivity and decreased MBL immunoreactivity characterise first-time pathologic first-trimester miscarriage: a case-control study.

The role of the complement system in first-time pathologic first-trimester miscarriage was investigated. In this case-control study, tissue samples of 126 women with pathologic miscarriage and termination of normal pregnancies were assessed. The pathologic pregnancy group consisted of 40 women with missed miscarriage, 13 women with incomplete miscarriage and 10 women with a blighted ovum. The control group consisted of 63 normal-appearing pregnancies. Immunoreactivity for C4d, Bb and MBL was evaluated in the deciduas and villous trophoblasts separately using a semi-quantitative histological scoring system (H-score). C4d and Bb H-scores were higher and MBL H-score was reduced in the deciduas and villous tissues from pathologic miscarriage compared to termination of pregnancies (p = .003 and p = .001; p = .011 and p < .001; p < .001 and p < .001, respectively). C4d and Bb activities were increased and MBL activity was decreased in human first-time pathologic first-trimester miscarriage. We suggest that three complement pathways may play a role in human first-time pathologic first-trimester miscarriage. Impact statement Previous studies focussed on complement proteins related to a single complement pathway in cases often associated with antiphospholipid syndrome (APS) or recurrent miscarriage. In APS-related cases, the classical pathway is activated. In antibody-dependent and in antibody-independent mouse models of foetal loss, classical and alternative pathways are activated, respectively. Lectin pathway deficiency has been reported in some recurrent miscarriage. The complement pathway or pathways, which have a role in human pathologic miscarriage was the starting point of this study. There has been no study done till now reporting the role of the three complement pathways in human pathologic miscarriage. In this study, we found increased classical and alternative complement pathway activities and decreased lectin pathway activity in tissues from first-time pathologic human miscarriage.

Macrophage activation syndrome in adult systemic lupus erythematosus: report of seven adult cases from a single Italian rheumatology center.

The aim was to describe the macrophage activation syndrome (MAS), a life-threatening syndrome characterized by excessive immune activation that can be triggered by conditions affecting immune homeostasis, in a cohort of adult Italian patients with systemic lupus erythematosus (SLE). This was a monocentric retrospective evaluation. The utility of the H-score, developed to estimate the individual risk of having reactive MAS in adult patients, was assessed. Among 511 patients with SLE, 7 cases (1.4%) of MAS (all females) were identified and their medical records reviewed. In all cases, MAS was simultaneous to the onset of SLE. All patients had fever, lymphadenopathy, hematological involvement, and high titer of anti-dsDNA antibodies. Workup for infections and malignancies was negative. In all cases, the H-score was higher than the cut-off suggested for the classification of reactive MAS. All cases required hospital admission, and 2 patients were admitted to the intensive care unit. Most patients were treated successfully with high doses of corticosteroids and with immunosuppressive drugs, whereas the full therapeutic regimen developed for primary hemophagocytic lymphohistiocytosis HLH was used only in one case. No death from MAS was observed. MAS is a rare and severe disorder that complicated the onset of SLE in our cohort. The H-score may be useful in the classification of these patients.

Role of quantitative p16INK4A mRNA assay and digital reading of p16INK4A immunostained sections in diagnosis of cervical intraepithelial neoplasia.

Visual interpretation of cervical biopsies is subjective and variable, generally showing fair to moderate inter-reader agreement in distinguishing high from low grade cervical intraepithelial neoplasia (CIN). We investigated the performance of two objective p16 quantitative tests in comparison with visual assessment: (i) p16-mRNA assay and (ii) digital analysis of sections stained for p16 protein. The primary analysis considered 232 high-risk human papilloma virus positive (HPV+) samples from diagnostic cervical specimens. A p16 RT-qPCR (p16-mRNA assay) was run on mRNA extracted from formalin-fixed paraffin-embedded sections. Two p16 immunohistochemistry (IHC) readings, a visual read by a histopathologist (Visual IHC) and a digital read of a high-resolution scan (Digital IHC), were done on adjacent sections. The worst reviewed CIN grade (agreed by at least two histopathologists) from up to two biopsies and a loop excision was taken, with CIN2/3 as the primary endpoint. Visual IHC attained a specificity of 70% (95%CI 61-77) for 85% (95%CI 77-91%) sensitivity. The four-point Visual IHC staining area under the curve (AUC) was 0.77 (95%CI 0.71-0.82), compared with 0.71 (95%CI 0.64-0.77) for p16-mRNA and 0.67 (95%CI 0.60-0.74) for Digital IHC. Spearman rank-order correlations were: visual to p16-mRNA 0.41, visual to digital 0.49 and p16-mRNA to digital: 0.22. The addition of p16-mRNA assay to visual reading of p16 IHC improved the AUC from 0.77 to 0.84 (p = 0.0049). p16-mRNA testing may be complementary to visual IHC p16 staining for a more accurate diagnosis of CIN, or perhaps a substitute in locations with a lack of skilled pathologists.

Comparison of immunoreactive score, HER2/neu score and H score for the immunohistochemical evaluation of somatostatin receptors in bronchopulmonary neuroendocrine neoplasms.

AIMS: Due to the growing number of somatostatin receptor (SSTR) targeting analogues and radiopeptides used for the diagnosis and therapy of neuroendocrine neoplasms (NEN), the assessment of SSTR subtype status has increasingly gained predictive value. In pathology, the SSTR protein levels are detected routinely by immunohistochemistry (IHC); however, a lack of a standardized evaluation system persists. Thus, in the present investigation, three well-established semi-quantitative scoring systems [immunoreactive score (IRS), human epidermal growth factor receptor 2 (HER2)/neu score, H score] used commonly for SSTR-IHC evaluation in NEN were compared. METHODS AND RESULTS: A total of 240 formalin-fixed, paraffin-embedded tumour samples from 90 patients with bronchopulmonary NEN were examined by IHC and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for SSTR1, 2A, 3, 4 and 5 expression. Using both methods, SSTR1, 2A and 5 were the most frequently expressed subtypes. For all SSTR subtypes, all three scores correlated well with each other and with qRT-PCR data. However, the IRS was the most meaningful score with the best correlation to mRNA levels. CONCLUSIONS: Because a unified IHC scoring system for SSTR analysis is needed urgently to optimize the theranostics of NEN, among the scores tested, the IRS seems to be the most suitable according to our results. It provides sufficient accuracy combined with high practicability.

Performances of the H-score and the HLH-2004 score in the positive diagnosis of secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphocytosis (HLH) is a rare clinical and biological entity that can be life-threatening. Early diagnosis can improve the overall prognosis of HLH. OBJECTIVES: The aims of this study are to evaluate the performances of HLH-2004-score and H-score in identifying patients with secondary HLH and to determine an optimal H-score cut-off for our population. METHODS: A retrospective study that involved all patients, with images of hemophagocytosis in myelograms analyzed at the laboratory of hematology, followed at these departments: clinical-hematology, internal-medicine, infectious-diseases and gastroenterology, University-Hospital "Hédi-Chaker", Sfax-Tunisia, (June2017-May2021). We identified two groups of patients: "HLH" and "Not-HLH". Then, for each patient, we calculated the HLH-2004-score and the H-score. RESULTS: Forty-two patients were included in this study. Twenty-five (60 %) belonging to group "HLH" and seventeen (40 %) to group "Not-HLH" with a mean age (38.72 vs. 39.82 years, p = 0.846) respectively. The study of the performances demonstrated that H-score had better performances. The best cut-off value of H-score for our population was 158.5, allowing a gain in sensitivity (from 92 % to 96 %) compared to the original study cut-off of 169. CONCLUSION: Both H-score and HLH-2004-score showed excellent discriminative powers with better performances for H-score. The new H-score cut-off at 158.5 can be applied to our population.

[Quantification of CDX2 using H-Score and its prognostic value in colon cancer]. / Cuantificación del CDX2 mediante el H-Score y su valor pronóstico en el cáncer colorrectal.

Colorectal cancer is the third tumor with the highest incidence in the world population and is the second cause of death according to the Globocan study. CDX2 has been acquiring an important role as a sensitive and specific marker in the diagnosis of colorectal cancer. However, the lack of inclusion of this marker in the pathology guidelines together with the lack of existing studies prevent its daily use. Although multiple studies relate the absence of staining to a worse prognosis, the literature does not define how intense the staining must be to be considered positive or negative. In the present study, the H-Score is described as a method to determine the positivity of CDX2 staining, using free access software called QuPath with a sample of 169 patients. Furthermore, it is suggested that those patients whose tumors had an H-Score for CDX2 less than or equal to 152 points had a significantly shorter recurrence-free interval time compared to those with an H-Score greater than this threshold. For this reason, this study aims to highlight the importance of quantification using digital pathology, as it could be applied in daily practice, and suggests a reference value for CDX2 from which the tumor prognosis may differ.

Urokinase Plasminogen Activator Receptor: An Important Focal Player in Chronic Subdural Hematoma?

Chronic subdural hematoma (CSDH) development involves inflammatory, angiogenetic, and fibrinolytic mechanisms, several components of which are now unraveled through intensive research. The urokinase plasminogen activator receptor (uPAR) is part of the plasminogen activator system and possesses inflammatory, angiogenetic, and fibrinolytic capabilities. As a first, this study aims to identify uPAR in the hematoma fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH and, if present, to investigate if the uPAR level at the time of surgery may be a predictor for later developing recurrent CSDH. uPAR expression in the hematoma membrane and dura mater was analyzed using immunohistochemistry and presented as the H-score of the positive immunostaining. The uPAR levels in the hematoma fluid and systemic blood were determined using a multiplex antibody bead kit (Luminex). Samples were collected at the time of the first CSDH surgery, and in the case of recurrent CSDH within 90 days, the samples were again collected at reoperation. A comparison of uPAR expression between the hematoma membrane and dura mater, as well as uPAR levels in systemic blood and hematoma fluid, was performed using the Wilcoxon rank sum test. We included 112 patients, 26 of whom had recurrent CSDH. The median hematoma uPAR level was 22,125 (14,845-33,237) and significantly higher than the median systemic blood level of 789 pg/L (465-2,088) (p < 0.001). Similarly, the uPAR level of the hematoma membrane was 14.3 (7.54-44.8) and significantly higher than the dural uPAR level of 0.81 (0.3-1.98) (p < 0.001). For the first time, we identified uPAR in the subdural fluid, hematoma membrane, dura mater, and systemic blood from patients with CSDH. The high expression of uPAR in the subdural fluid and hematoma membrane indicates that the mechanisms of CSDH are predominantly in the subdural fluid collection and surrounding hematoma membrane.

A rare case report of hemophagocytic lymphohistiocytosis secondary to pure eythroid leukemia in a person living with HIV.

Pure erythroid leukemia (AML-M6) is a rare variant of acute myeloid leukemia (AML) with predominant erythroid lineage proliferation. The incidence of AIDS defining cancers including Kaposi sarcoma and non-Hodgkins lymphoma are on declining trends due to effective use of HAART (Highly Active Antiretroviral Therapy). Correspondingly, there have been increasing cases of leukemia in persons living with HIV. Our case is a 43 years old male living with HIV who was admitted with high grade fever and mucosal bleeds. On examination, he had periorbital swelling and ecchymosis with hepatosplenomegaly. The laboratory investigations revealed bicytopenia with high ferritin, low fibrinogen and hypertriglyceridemia. A diagnosis of hemophagocytic lymphohistiocytosis (HLH) with H score of 222 was made. Bone marrow examination revealed hypercellular marrow with more than 80% cells of erythroid lineage with 47% proerythroblasts. Suggesting pure erythroid leukemia (AML-M6). This diagnosis with secondary HLH carries a very poor prognosis in persons living with HIV.

The Impact of DTYMK as a Prognostic Marker in Colorectal Cancer.

Background: Overexpression of deoxythymidylate kinase (DTYMK) has been associated with more aggressiveness and pathological behaviors in hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC). However, the expression of DTYMK and its prognostic significance in colorectal cancer (CRC) patients are yet unknown. The goal of this study was to investigate the DTYMK immunohistochemistry reactivity in CRC tissues and to see how it correlated with various histological and clinical features as well as survival. Methods: Several bioinformatics databases and two tissue microarrays (TMAs) of 227 cases were used in this study. Immunohistochemistry assay was used to study the protein expression of DTYMK. Results: Based on the GEPIA, UALCAN, and Oncomine databases, DTYMK expression has increased in tumor tissues at both RNA and protein levels in colorectal adenocarcinoma (COAD) compared to normal tissues. A high DTYMK H-score was found in 122/227 (53%) of the cases, whereas a low DTYMK H-score was found in 105/227. The age at diagnosis (P = 0.036), stage of the disease (P = 0.038), and site of origin (P = 0.032) were all linked to a high DTYMK H-score. Patients with high level of DTYMK had bad overall survival. Interestingly, high DTYMK protein level was associated with PSM2 (P = 0.002) and MSH2 (P = 0.003), but not with MLH2 or MSH6. Conclusion: This is the first study to cover the expression and prognostic significance of DTYMK in CRC. DTYMK was upregulated in CRC and could be considered as a prognostic biomarker.

Lack of correlation between MET and PD-L1 expression in non-small cell lung cancer revealed by comparative study of matched biopsies and surgical resection samples.

INTRODUCTION: Both MET expression and the PD-L1 tumor proportion score (TPS) are companion diagnostics for treatment of advanced non-small cell lung carcinoma (aNSCLC) patients. We evaluated the rate of correlation between MET expression and the PD-L1 TPS in matched biopsies and surgically resected specimens from NSCLC patients. PATIENTS AND METHODS: This retrospective analysis assessed the prevalence and correlation between MET expression (SP44 clone) and the PD-L1 TPS (22C3 clone) by immunohistochemistry together with molecular alterations determined by targeted next-generation sequencing in matched lung biopsy and surgically lung resected specimens from 70 patients with NSCLC. RESULTS: The study found a significant correlation between the MET H-score in surgical samples and matched biopsies (P-value < 0.0001), as well as between the PD-L1 TPS in paired biopsies and surgical samples (P-value < 0.0001). However, there was no significant correlation between the MET H-score or expression subgroups and the PD-L1 TPS in both types of paired samples (P-value = 0.47, and P-value = 0.90). The MET H-score was significantly higher in adenocarcinoma compared to squamous cell carcinoma (P-value < 0.0001). A mutational analysis showed that the MET H-score was significantly higher in NSCLC cases with targetable molecular alterations (P-value = 0.0095), while no significant correlation was found for the PD-L1 TPS. CONCLUSIONS: Our study found no significant correlation between PD-L1 and MET expression in samples from NSCLC patients, highlighting the importance of personalized treatment strategies based on individual expression profiles. These findings provide valuable insight into the development of effective immunotherapy and targeted therapy for NSCLC patients.