Journal of Clinical Pathology最新文献

Aims: Concerns over population-level immunity have been heightened with each successive wave of COVID-19, prompting questions about whether it is primarily derived from vaccination efforts or from previous natural infections with the virus. We wished to determine the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in Pretoria (Tshwane), South Africa, and to establish whether they were derived from vaccination or natural infection.

Methods: Serum samples were collected from HCWs during the fourth wave of COVID-19 between 1 December 2021 and 13 March 2022. The samples were tested using the Abbott SARS-CoV-2 Spike IgG (S-IgG), IgM (S-IgM) and the SARS-CoV-2 Nucleocapsid IgG (NC-IgG) kits.

Results: Of the 221 participants, 76% (n=168) were women and 24% (n=53) were men. A total of 96.4% (n=213) of the participants were vaccinated. Natural infection-derived antibodies were detected in 23% (n=51) of participants, and vaccine-derived antibodies in 74% (n=164) of the HCWs.

Conclusions: Even after three waves of COVID-19, HCWs derived most of their detectable antibodies from vaccination. Vaccination remains an essential tool to protect HCWs and patients from SARS-CoV-2 infection.

Despite advances in cancer immunotherapies across various cancers, survival outcomes in colorectal cancer (CRC) with these agents remain largely unsatisfactory despite the high tumour burden. Colorectal stem cells (CSCs), especially LGR5+ CSCs, are the significant drivers in CRC initiation, progression and resistance to conventional therapies. Although native immune surveillance is sufficient to combat early tumour formation, CRC evades early immune detection with its well-documented adenoma-to-carcinoma sequence. The exact mechanism underlying this phenomenon still needs to be better understood. SRY-related HMG box gene 17 (SOX17), a transcription factor that specifies embryonic gut formation, is increasingly recognised as a significant factor in CRC tumourigenesis. However, its role as a tumour suppressor or oncogene is still debated. Evidence from a recent study highlighted the critical role of SOX17 in reshaping the tumour immune ecosystem through the simultaneous inhibition of CD8+ T cells and selective suppression of LGR5 expression in CSCs through transcriptional repression, thereby facilitating disease progression. Given its role in immune evasion, SOX17 could be a promising marker in personalised therapy. Additionally, SOX17 could play a role in the diagnostic arena, potentially identifying dysplasia in the gastrointestinal tract. Future clinical, basic and genetic studies focusing on SOX17 are needed to ascertain its mechanistic role in tumour immunomodulation in CRC and diagnosing preneoplastic lesions in the gastrointestinal tract.

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.

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.