Journal of Clinical Pathology最新文献

Aim: Hereditary spherocytosis (HS) refers to a heterogeneous disorder varying in genotypic and phenotypic features manifested by the production of spherocytes. The diseased cells can be eliminated from the circulatory system either by macrophages in the spleen in the extravascular pathway or the intravascular pathway via the complement cascade. This study aimed to investigate the status of red blood cell (RBC) surface molecules CD55 (decay accelerating factor), CD35 (complement receptor type 1-CR1), CD59 (MACIF), CD47 (marker of self) and CD71 (transferrin receptor) from individuals diagnosed with HS.

Methods: This study aims to quantitatively assess RBC surface molecules (CD35, CD55, CD59, CD47 and CD71) on peripheral RBCs from 42 HS patients and 30 healthy controls, carried out by flow cytometry using monoclonal antibodies.

Results: Our findings show that HS patients had a significant 58% decrease in anti-CD35 binding compared with healthy controls. This is the first study to demonstrate the presence of erythrocytes with reduced CD35 levels in HS patients. Compared with the control group, HS patients had comparable levels of CD59 and CD47, but their CD55 levels were significantly reduced, with a 30% decrease in anti-CD55 binding. The expression level of CD71 was higher in HS patients (3.33%) compared with healthy controls in our study.

Conclusion: The diminished levels of CD35 and CD55 in HS patients may influence RBC clearance, possibly through mechanisms that remain fully understood and require further investigation, including their potential role in haemolytic crises. Further research employing molecular techniques is required to clarify their exact role in HS.

Aims: Current guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited. We aimed to elucidate histological characteristics influencing salvage ER success in patients with low-stage, pretreated EAC.

Methods: We retrospectively reviewed 272 EAC tumours postoesophagectomy from five US centres and collected clinicopathological data including discontinuous growth (DG), defined as separate tumour foci ≥2 mm from the main tumour. We selected 101 patients with low-stage disease and divided them into treatment-naïve (n=70) and neoadjuvant therapy (n=31) groups. We compared the two groups and differences in clinical, histological and outcome characteristics were identified.

Results: In the entire cohort (n=272), DGs were identified in 22% of cases. Multivariate analysis revealed DGs as an independent prognostic factor for recurrence and positive oesophagectomy margins. Lymphovascular invasion (LVI) and background intestinal metaplasia predicted DG presence and absence, respectively. Compared with the treatment-naïve low T-stage subgroup, the pretreated subgroup exhibited higher incidence of poorly differentiated carcinoma (16% vs 46%, p=0.007), larger tumours (14 vs 30 mm, p<0.001), higher tumour, node, metastases stage (7% vs 30%, p=0.004), more nodal disease (7% vs 36%, p<0.001) and frequent DGs (1% vs 13%, p=0.030).

Conclusions: In treated low T-stage EACs, DGs may contribute to suboptimal outcomes following salvage ER. Presence of LVI (as a surrogate for DGs) and poor differentiation in the absence of intestinal metaplasia in biopsy samples may serve as histological poor prognosticators in treated patients with EAC being considered for salvage ER.

Aims: Triple-negative breast cancer (TNBC) is prognostically and therapeutically heterogeneous. The mitotic activity index (MAI) and fibrotic focus (FF) have been established as predictors in non-TNBC but not in TNBC. Late distant metastases occur in TNBC, but previous studies had short follow-up. High stromal tumour-infiltrating lymphocytes (sTILs) are prognostically favourable, but prognostic sTILs-thresholds are not well assessed. We evaluated prognostic/predictive characteristics in an observational population-based cohort of 231 consecutive TNBC patients with long follow-up.

Methods: MAI, FF, sTILs and other characteristics were analysed with standard receiver operating characteristic curve analysis, percentile-derived prognostic thresholds, univariate and multivariate survival methods. A TNBC index and decision tree were assessed for distant metastasis-free survival.

Results: Long follow-up was decisive: 7% of patients developed late distant metastases. In agreement with the aggressive nature of TNBC, the strongest prognostic MAI-threshold was 5 (p=0.001), lower than that for non-TNBC phenotypes. Lymph-node (LN) status (p=0.0003), FF (p=0.002), MAI5 (p=0.009) and sTILs (threshold 40%, p=0.003) were multivariable based significant and independent prognosticators, but no other characteristics (age, tumour size and grade). LN status was the strongest prognosticator, followed by FF, MAI5 and sTILs40. Subgroup analyses of patients undergoing adjuvant chemotherapy (ACT) showed that only FF and sTILs had significant prognostic value, while LN-positivity and the combination of LN-positivity and MAI≥5 could be a predictive factor for ACT outcome.

Conclusions: LN status, MAI5, FF and sTILs40 are prognostic factors in TNBC patients. In TNBC patients who have undergone ACT, the combination of LN-positivity and MAI5 is predictive for response to treatment.

We investigated the prognostic impact of blast counts, TP53 allelic state determinants (number of hits, del(17p), variant allele frequency, complex karyotype),and a novel karyotypic clonal cell fraction (≤50% clonal cells vs >50% clonal cells (termed 'CK50')) in 495 individuals with TP53-mutated (TP53^MUT ) myeloid neoplasms. Outcome examined was 24-month survival (OS24). The cohort (median age 71) included 29% (144/495) myelodysplastic syndromes (MDS)/MDS-acute myeloid leukaemia (AML) (1%-19% blasts) and 71% (351/495) AML (≥20% blasts), with 18% (81/460) having low CK50. Overall, 83% received front-line hypomethylating agents. Higher blast counts (<20% vs ≥20%) were marginally associated with CK50 (p=0.08). In the OS24 analysis, blast count showed a marginal association with OS24 (HR 1.3 (95% CI 1.0 to 1.6); p=0.07), while CK50 predicted significantly inferior outcomes (HR=1.7 (95% CI 1.2 to 2.3); p=0.002). In a multivariable model including all TP53 allelic state determinants, only CK50 and complex karyotype remained relevant for predicting adverse outcomes.

Aims: Accurate determination of histological activity in ulcerative colitis (UC) is essential given its diagnostic and prognostic importance. Data on the relationship between histology and immune cell markers are limited. We aimed to evaluate the association between histological disease activity and immune cell marker concentration in colonic biopsies from patients with UC.

Methods: Sigmoid colon biopsies from 20 patients with UC were retrospectively assessed using the Robarts Histopathology Index (RHI). Targeted mass spectrometry determined the concentration of 18 immune cell markers (cluster of differentiation (CD) 4, CD8, CD19, CD20, CD40, CD56, CD68, CD103, forkhead box p3 (FOXP3), human leucocyte antigen, DR alpha chain (HLA-DRA), interleukin 10 (IL-10), IL-23 subunit alpha (IL-23A), IL-23 receptor (IL-23R), IL-2 receptor alpha chain (IL-2RA), Ki67, lymphocyte-activation gene 3 (LAG-3), programmed cell death protein 1 (PD-1) and PD ligand 1 (PD-L1)). The association between RHI score and immune cell marker concentration was quantified using Spearman's rank correlation coefficient (ρ) and related 95% CIs.

Results: Fourteen of the 18 immune cell marker proteins were detected, with tissue concentration ranging from 0.003 to 11.53 fmol/µg. The overall RHI score was positively correlated with CD19, CD20, CD40, FOXP3, LAG-3, PD-1 and PD-L1 concentration (ρ=0.596-0.799) and negatively correlated with CD56 concentration (ρ=-0.460). There was no significant association between RHI score and CD4, CD8, CD68, CD103, HLA-DRA or Ki67 concentration.

Conclusions: This study provides insight into the correlation between immune cell marker expression and histological disease activity and the possible molecular and immunological determinants underlying microscopic disease activity in UC.