Expression of S-locus inhibitor gene (Sli) in various diploid potatoes

Current guidelines recommend immunosuppressive treatment (IT) in patients with primary sclerosing cholangitis (PSC) and elevated aminotransferase levels more than five times the upper limit of normal and elevated serum IgG-levels above twice the upper limit of normal. Since there is no evidence to support this recommendation, we aimed to assess the criteria that guided clinicians in clinical practice to initiate IT in patients with previously diagnosed PSC.This is a retrospective analysis of 196 PSC patients from seven German hepatology centers, of whom 36 patients had received IT solely for their liver disease during the course of PSC. Analyses were carried out using methods for competing risks.A simplified autoimmune hepatitis (AIH) score >5 (HR of 36, p5 and a mHAI score >3, suggesting concomitant features of AIH, influenced the decision to introduce IT during the course of PSC. In German clinical practice, the cutoffs used to guide IT may be lower than recommended by current guidelines

NTRK fusion protein expression is absent in a large cohort of diffuse large B-cell lymphoma

BackgroundEven though two NTRK-targeting drugs are available for the treatment of irresectable, metastatic, or progressive NTRK-positive solid tumors, less is known about the role of NTRK fusions in lymphoma. For this reason, we aimed to investigate if NTRK fusion proteins are expressed in diffuse large B-cell lymphoma (DLBCL) by systemic immunohistochemistry (IHC) screening and additional FISH analysis in a large cohort of DLBCL samples according to the ESMO Translational Research and Precision Medicine Working Group recommendations for the detection of NTRK fusions in daily practice and clinical research.MethodsA tissue microarray of 92 patients with the diagnosis of DLBCL at the University Hospital Hamburg between 2020 and 2022 was built. The clinical data were taken from patient records. Immunohistochemistry for Pan-NTRK fusion protein was performed and positive staining was defined as any viable staining. For FISH analysis only results with quality 2 and 3 were evaluated.ResultsNTRK immunostaining was absent in all analyzable cases. No break apart was detectable by FISH.ConclusionOur negative result is consistent with the very sparse data existing on NTRK gene fusions in hematologic neoplasms. To date, only a few cases of hematological malignancies have been described in which NTRK-targeting drugs may provide a potential therapeutic agent. Even though NTRK fusion protein expression was not detectable in our sample cohort, performing systemic screenings for NTRK fusions are necessary to define further the role of NTRK fusions not only in DLBCL but in a multitude of lymphoma entities as long as the lack of reliable data exists

Trophoblast Cell Surface Antigen 2 (Trop2) Is Expressed in Cases of EBV-Positive Diffuse Large B-Cell Lymphoma Emerging from Angioimmunoblastic T-Cell Lymphoma

Although trophoblast cell surface antigen 2 (Trop2)-targeting drugs are already approved or under investigation in various solid tumors, the significance of Trop2 in lymphoma is unknown. Thus, our objective was to investigate the expression of Trop2 in diffuse large B-cell lymphoma (DLBCL) through a systemic immunohistochemistry screening. We constructed a tissue microarray comprising tissue from 92 DLBCL patients, each diagnosed at the University Medical Center Hamburg-Eppendorf (2020–2022). Trop2-immunohistochemistry was carried out, and positive staining was deemed a specific membranous positivity. Four samples were derived from Epstein-Barr virus (EBV)-positive DLBCL, with one case of EBV-positive DLBCL following angioimmunoblastic T-cell lymphoma (AITL). Strong Trop2 immunostaining was detectable in 1 of 91 analyzable samples, originating from a patient with a composite EBV-positive DLBCL emerging from AITL. Therefore, we performed an additional database search to identify all cases of composite EBV-positive DLBCL emerging from AITL since 2015. Five additional cases were identified and stained for Trop2, revealing two cases with strong B-blast positivity. Our preliminary data imply that Trop2 appears absent in de novo DLBCL, whereas Trop2 is strongly expressed in cases of a rare variant of EBV-positive DLBCL. Further investigations are needed to confirm our results, particularly on the subset of EBV-positive DLBCL emerging from AITL

Upregulation of the heterogeneous nuclear ribonucleoprotein hnRNPA1 is an independent predictor of early biochemical recurrence in TMPRSS2:ERG fusion-negative prostate cancers

Heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1) is a ubiquitous RNA splicing factor that is overexpressed and prognostically relevant in various human cancer types. To study the impact of hnRNPA1 expression in prostate cancer, we analyzed a tissue microarray containing 17,747 clinical prostate cancer specimens by immunohistochemistry. hnRNPA1 was expressed in normal prostate glandular cells but often overexpressed in cancer cells. hnRNPA1 immunostaining was interpretable in 14,258 cancers and considered strong in 33.4%, moderate in 45.9%, weak in 15.3%, and negative in 5.4%. Moderate to strong hnRNPA1 immunostaining was strongly linked to adverse tumor features including high classical and quantitative Gleason score, lymph node metastasis, advanced tumor stage, positive surgical margin, and early biochemical recurrence (p < 0.0001 each). The prognostic impact of hnRNPA1 immunostaining was independent of established preoperatively or postoperatively available prognostic parameters (p < 0.0001). Subset analyses revealed that all these associations were strongly driven by the fraction of cancers lacking the TMPRSS2:ERG gene fusion. Comparison with other key molecular data that were earlier obtained on the same TMA showed that hnRNPA1 overexpression was linked to high levels of androgen receptor (AR) expression (p < 0.0001) as well as presence of 9 of 11 chromosomal deletions (p < 0.05 each). A strong association between hnRNPA1 upregulation and tumor cell proliferation that was independent from the Gleason score supports a role for tumor cell aggressiveness. In conclusion, hnRNPA1 overexpression is an independent predictor of poor prognosis in ERG-negative prostate cancer. hnRNPA1 measurement, either alone or in combination, might provide prognostic information in ERG-negative prostate cancer

Univariate analysis of potential risk factors for IT as first event after UDCA prescription (using Cox' model) at first presentation.

<p>* = after first screening by colonoscopy</p><p>Univariate analysis of potential risk factors for IT as first event after UDCA prescription (using Cox' model) at first presentation.</p

Liver histologies of PSC patients with a mHAI score greater and lower than 3 points.

<p>A: typical concentric fibrosis and low grade of inflammation. B: typical periductular fibrosis and additionally signs of interface hepatitis (*), representing a patient with a mHAI score of 8/18. Staining: hematoxylin eosin.</p

Cumulative probability of introduction of IT in the presence of competing risks at the time of PSC diagnosis (start of UDCA prescription): Alkaline phosphatase (AP), bilirubin, alanine aminotransferase (ALT), immunoglobulin G (IgG).

<p>Cumulative probability of introduction of IT in the presence of competing risks at the time of PSC diagnosis (start of UDCA prescription): Alkaline phosphatase (AP), bilirubin, alanine aminotransferase (ALT), immunoglobulin G (IgG).</p

Histological disease activity and simplified AIH score as single risk factors for IT in patients with PSC.

<p>* Including patients with/without histological assessment considering maximum points of histological score still leading to ≤ 5 points.</p><p>Histological disease activity and simplified AIH score as single risk factors for IT in patients with PSC.</p

Histological characteristics in patients with and without IT.

<p>* <i>A</i>: <i>periportal or periseptal interface hepatitis (piecemeal necrosis); B</i>: <i>confluent necrosis; C</i>: <i>focal lytic necrosis</i>, <i>apoptosis</i>, <i>and focal inflammation; D</i>: <i>portal inflammation</i>.</p><p>Histological characteristics in patients with and without IT.</p