Immune checkpoint inhibitors (ICI) are recently introduced in the management of various cancers. There are three main immunotargets as follows: Cytotoxic T-lymphocyte antigen-4 (CTLA4), programmed ...death 1 (PD-1) and programmed death ligand-1 (PD-L1). These three targets are under investigation for therapeutic, predictive and prognostic purposes in genitourinary cancers. There is a need for predictive biomarkers of immunotherapy to optimize treatment, to limit side-effects and to reduce the costs of therapy. This review focuses on the role of pathologic applications in the selection of patients with genitourinary cancer who are potentially responsive to immunotherapy. PD-L1 expression by immunohistochemistry, tumor mutation burden and microsatellite instability status are mainly discussed.
Objectives
We aim to investigate the association between serum B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) levels with disease activity and clinical findings in SLE ...patients.
Methods
Seventy-nine patients with SLE and 27 healthy controls were included into the study. Serum BAFF and APRIL levels were measured by using ELISA. In 19 patients with active disease at the time of the assessment, BAFF/APRIL levels were reassessed after 6 months of follow-up and disease activity was evaluated by using SLEDAI-2K. The relationship between renal histopathology index scores and lupus nephritis (LN) classes with serum BAFF/APRIL levels was examined in 16 patients who had recent renal involvement and underwent biopsy during the study.
Results
Although both BAFF/APRIL levels were higher in patients with SLE compared to the control group (p < 0.001), no correlation was found between BAFF/APRIL levels and SLEDAI scores. Serum BAFF levels were higher in patients with renal disease activity (p = 0.01), and there was a significant correlation between APRIL levels and proteinuria (r = 0.42, p = 0.02). A weak inverse correlation was observed between BAFF and C3 levels (r = 0.25, p = 0.02). No correlation was found between BAFF/APRIL levels and renal SLEDAI scores, renal histopathology, activity, and chronicity index scores. In the active disease group after treatment, there was no significant change in serum BAFF levels, but a significant increase in serum APRIL levels was observed.
Conclusion
These results suggest that both cytokines are involved in the pathogenesis of SLE and that serum BAFF can be valuable as a biomarker in SLE especially in patients with renal activity.
Background. The sinonasal tract is the second most common site of human papillomavirus (HPV)-related carcinomas in the head and neck. Published data on the association between sinonasal tumors and ...HPV are quite inconsistent among different regions. Material and methods. We performed high-risk HPV DNA in situ hybridization (ISH) and p16 immunohistochemistry on sinonasal carcinomas diagnosed between 2006 and 2016. Results. Of 105 sinonasal carcinomas, we found only two (2%) HPV-positive cases; both had non-keratinizing morphology and were diffusely positive for p16. By histologic type, HPV DNA positivity rate was 14% in non-keratinizing squamous cell carcinomas, and we did not detect HPV DNA in any other type of sinonasal carcinomas. Thirteen HPV-negative tumors (7 salivary gland carcinomas, 3 sinonasal undifferentiated carcinomas, 2 keratinizing squamous cell carcinomas, and 1 non-keratinizing squamous cell carcinoma) were positive for p16. In nine carcinomas arising from an underlying sinonasal papilloma, p16 and HPV DNA ISH were evaluated in both carcinoma and papilloma areas and all were negative. Follow-up information was available for 104 patients; 46 (44%) were alive and 58 (55%) died of disease. One of the two HPV-positive patients died of the disease; the other was alive at 100 months of follow-up. Conclusions. We detected a much lower percentage of HPV positivity in sinonasal carcinomas when compared to the literature. We believe that our results support various rates of HPV-related carcinomas depending on the geographic and ethnic characteristics.
ObjectiveDiffuse large B-cell lymphoma (DLBCL) is a biologically heterogeneous disease that is classified into germinal center B-cell (GCB) and non-GCB subtypes, which are prognostically different. ...The Hans algorithm is the most widely used tool based on CD10, BCL6, and MUM1 expression, but some cases with the non-GCB phenotype are still known to be misclassified. In this study, we investigate the extent to which GCET1, HGAL, and LMO2 protein expressions reflect GCB phenotype together with their roles in determining the GCB phenotype of DLBCL and their contributions to the performance of the Hans algorithm. Materials and MethodsSixty-five cases of DLBCL-not otherwise specified, 40 cases of follicular lymphoma (FL), and 19 non-GC-derived lymphoma cases were included in this study. The DLBCL cases were grouped as CD10+ (Group A) or only MUM1+ (Group B), and the remaining cases constituted the intermediate group (Group C). GCET1, HGAL, and LMO2 expressions were evaluated. ResultsIn the FL group, GCET1, HGAL, and LMO2 were positive in 85%, 77.5%, and 100% of the cases, respectively. Among the non-GC-derived lymphoma cases, all three markers were negative in cases of small lymphocytic lymphoma, plasmablastic lymphoma, peripheral T-cell lymphoma, and anaplastic large cell lymphoma. GCET1 and HGAL were negative in cases of marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL). Two of the 3 MZL and 2 of the 4 MCL cases were positive for LMO2. In the DLBCL group, the number of cases with GCET1, HGAL, and LMO2 positivity was 18 (90%), 17 (85%), and 20 (100%), respectively, in Group A and 0 (0%), 2 (13.3%), and 2 (13.3%), respectively, in Group B. Considering these rates, when the cases in the intermediate group were evaluated, it was concluded that 13 cases typed as non-GCB according to the Hans algorithm may have the GCB phenotype. ConclusionGCET1, HGAL, and LMO2 are highly sensitive markers for determining the germinal center cell phenotype and can increase the accuracy of the subclassification of DLBCL cases, especially for cases that are negative for CD10.
Age at onset has been shown to affect the clinical course and outcome of systemic lupus erythematosus (SLE). Herein, we aimed to define the differences in clinical characteristics, organ damage, and ...survival between patients with juvenile-onset (jSLE) and adult-onset SLE (aSLE).
For the study, 719 patients (76.9%) with aSLE and 216 (23.1%) with jSLE were examined. Comparisons between the groups were made for demographic characteristics, clinical features, auto-antibody profiles, damage, and survival rates.
These results were significantly more frequent in jSLE: photosensitivity, malar rash, oral ulcers, renal involvement, neuropsychiatric (NP) manifestations, and autoimmune hemolytic anemia (AIHA). Of the autoantibodies, a higher frequency of anti-dsDNA and anticardiolipin IgG and IgM were observed in the jSLE group. A significant proportion of patients with aSLE had anti-Sm positivity and pleuritis. The proportion of patients with jSLE who developed organ damage was comparable to that of patients with aSLE (53% vs 47%) and the mean damage scores were similar in both groups. Renal damage was significantly more frequent in jSLE while musculoskeletal and cardiovascular system damage and diabetes mellitus were more prominent in aSLE. Comparison of survival rates of the 2 groups did not reveal any significant differences.
We report a higher frequency in the jSLE group of renal involvement, cutaneous symptoms, oral ulcers, NP manifestations, AIHA, and anti-dsDNA positivity. A significant proportion of patients in the jSLE group had damage, most prominently in the renal domain. Our findings might support different genetic/environmental backgrounds for these 2 subgroups.
Aim
To investigate the relationship between serum PSA level, Gleason score of PCa and the outcomes of Ga
68
-PSMA PET/CT in patients with recurrent PCa.
Methods
A total of 109 consecutive patients ...(median age 71 years; range 48–89 years) who had PSA recurrence after RP and/or hormonotherapy and/or radiotherapy were included in this study. Local recurrences, lymph node metastasis (pelvic, abdominal and/or supradiaphragmatic), bone metastases (oligometastatic/multimetastatic) and other metastatic sites (lung, liver, brain, etc) were documented.
Results
In 91(83.4%) patients at least one lesion characteristic for PCa was detected by
68
Ga-PSMA PET/CT. The median serum total PSA (tPSA) was 6.5 (0.2–640) ng/ml.There was a significant difference between
68
Ga-PSMA PET/CT positive and negative patients in terms of serum total PSA value. No statistical significance was found between positive and negative
68
Ga-PSMA PET/CT findings in terms of Gleason score. Local recurrence was detected in 56 patients. whereas lymph node metastases were demonstrated in 46 patients. Pelvic nodal disease was the most frequent presentation followed by abdominal and supradiaphragmaticnodal involvement. Bone metastases oligometastasis, (
n
= 20); multimetastasis, (
n
= 35)⦌ were also detected in 55 patients. In the ROC analysis for the study cohort, the optimal cut-off value of total serum PSA was determined as 0.67 ng/ml for distinguishing between positive and negative
68
Ga-PSMA PET/CT images, with an area under curve of 0.952 (95% CI 0.911–0.993).
Conclusions
68
Ga-PSMA PET/CT was found to be an effective tool for the detection of recurrent PCa. Even though no relationship was detected between the GS and
68
Ga-PSMA PET/CT findings, serum total PSA values may be used for estimating the likelihood of positive
68
Ga-PSMA PET/CT results.
PDF
