13,048 publications found
Sort by
Refined criteria for p53 expression in ovarian mucinous tumours are highly concordant with TP53 mutation status, but p53 expression/TP53 status lack prognostic significance.

In gynecological neoplasms, immunohistochemical (IHC) expression of p53 is generally an accurate predictor of TP53 mutation status if correctly interpreted by the pathologist. However, the literature concerning cut-offs, frequency and prognostic significance of p53 staining in ovarian mucinous tumours is limited and heterogeneous. We performed an analysis of 123 primary ovarian mucinous tumours including mucinous borderline tumours (MBT), mucinous carcinomas (MC), and tumours with equivocal features between MBT and MC. We assessed p53 expression for the three recognised patterns of aberrant staining in ovarian carcinoma [overexpression ('all'), null and cytoplasmic] but using a recently suggested cut-off for aberrant overexpression in ovarian mucinous tumours (strong nuclear p53 staining in ≥12 consecutive tumour cells) and correlated the results with next generation sequencing (NGS) in all qualitatively sufficient cases (92/123). Aberrant p53 expression was present in 25/75 (33.3%) MBT, 23/33 (69.7%) MC (75% of MC with expansile invasion and 61.5% with infiltrative invasion), and 10/15 (66.7%) tumours equivocal between MBT and MC. Regarding the 92 tumours with paired IHC and mutation results, 86 showed concordant results and six cases were discordant. Three discordant MBT cases showed aberrant expression but were TP53 wild-type on sequencing. Three cases had normal p53 expression but contained a TP53 mutation. Overall, IHC predicted the TP53 mutation status with high sensitivity (94.1%) and specificity (92.7%). The accuracy of IHC was 93.5% with a positive predictive value of 94.1% and a negative predictive value of 92.7%. When comparing MC cases with wild-type TP53 versus those with TP53 mutation, there were no significant differences concerning disease-free survival, local recurrence-free survival, or metastases-free survival (p>0.05). In the MBT subgroup, there were no events for survival analyses. In conclusion, using an independent large sample set of ovarian mucinous tumours, the results of our study confirm that the suggested refined cut-off of strong nuclear p53 staining in ≥12 consecutive tumour cells reflect high accuracy, sensitivity and specificity for an underlying TP53 mutation but the TP53 mutation status has no prognostic significance in either MC or MBT.

Real world implementation of flow cytometric monocyte subset partitioning for distinguishing chronic myelomonocytic leukaemia from other causes of monocytosis.

Monocyte subset partitioning by flow cytometry may be a useful tool in distinguishing chronic myelomonocytic leukaemia (CMML) from other causes of monocytosis, however there has been varying success in real world implementation. Additionally, current assays require an individual tube for analysis despite significant overlap in antibodies used in routine T and NK cell analysis. The objective of this study was to validate a flow cytometry assay for the enumeration of monocyte subsets in our community-based laboratory and compare this to a hybrid panel allowing analysis of monocytes, T cells and NK cells in a single tube. Monocyte subset analysis was performed on peripheral blood samples of patients with monocytosis at the time of bone marrow biopsy or transient monocytosis in the setting of bacteraemia. Cut-offs of >94% classical and <1.13% non-classical monocytes for distinguishing CMML were assessed. Classical monocytes were significantly higher, and non-classical monocytes significantly lower in CMML compared to other causes of monocytosis. The sensitivity and specificity of >94% classical monocytes were 73% [95% confidence interval (CI) 43-90%] and 89% (95% CI 75-96%) regardless of which panel was used. Non-classical monocytes of <1.13% had a sensitivity and specificity of 82% (95% CI 52-97%) and 83% (95% CI 68-92%) with the monocyte panel and 55% (95% CI 28-78%) and 89% (95% CI 75-96%) using the hybrid panel. We have found the estimation of the classical monocyte subset to be the most robust and repeatable variation of this assay with sensitivity and specificity that is clinically useful. A hybrid panel may provide an effective approach to implementing monocyte subsets into practice.

Appl1, Sortilin and Syndecan-1 immunohistochemistry on intraductal carcinoma of the prostate provides evidence of retrograde spread.

The presence of intraductal carcinoma of the prostate (IDCP) correlates with late-stage disease and poor outcomes for patients with prostatic adenocarcinoma, but the accurate and reliable staging of disease severity remains challenging. Immunohistochemistry (IHC) has been utilised to overcome problems in assessing IDCP morphology, but the current markers have only demonstrated limited utility in characterising the complex biology of this lesion. In a retrospective study of a cohort of patients who had been diagnosed with IDCP, we utilised IHC on radical prostatectomy sections with a biomarker panel of Appl1, Sortilin and Syndecan-1, to interpret different architectural patterns and to explore the theory that IDCP occurs from retrograde spread of high-grade invasive prostatic adenocarcinoma. Cribriform IDCP displayed strong Appl1, Sortilin and Syndecan-1 labelling patterns, while solid IDCP architecture had high intensity Appl1 and Syndecan-1 labelling, but minimal Sortilin labelling. Notably, the expression pattern of the biomarker panel in regions of IDCP was similar to that of adjacent invasive prostatic adenocarcinoma, and also comparable to prostate cancer showing perineural and vascular invasion. The Appl1, Sortilin, and Syndecan-1 biomarker panel in IDCP provides evidence for the model of retrograde spread of invasive prostatic carcinoma into ducts/acini, and supports the inclusion of IDCP into the five-tier Gleason grading system.

Open Access
Inter-rater concordance of basal cell carcinoma subtypes: influences on reporting format and opportunities for further classification modifications.

Diagnosis of basal cell carcinoma (BCC) higher risk subtypes influences management strategies because of their propensity to recur locally. Subtyping is prone to inter-observer variability, and subtyping definitions are inconsistently applied. This study sought to compare the interobserver reproducibility of individual BCC subtypes using the 4th edition World Health Organization (WHO) Classification of Skin Tumours (CoST) definitions, with classification into lower and higher risk histological subtype groups. Ninety-one BCC cases were rated by seven pathologists, noting the presence of BCC subtype(s), and providing a higher or lower risk subtype grouping per case. Raters were provided with definitions as per the 4th edition WHO CoST for 10 listed BCC subtypes. Surgical specimen type was noted. Subgroup analysis was performed to exclude cases when the tumour deep front was not well visualised, or there was tangential sectioning (n= 6). Light's kappa was used to assess inter-rater reliability. From the total group (n= 91), five BCC subtypes showed a sufficient number of ratings for computing a κ statistic. From these five subtypes, superficial subtype showed substantial inter-rater agreement (κ= 0.64), and the other four subtypes showed moderate inter-rater agreement [nodular (κ= 0.45), sclerosing/morphoeic (κ= 0.45), infiltrating (κ= 0.49) and micronodular (κ= 0.57)]. Two-tiered rating into either higher or lower risk subtype showed substantial inter-rater agreement (κ= 0.72). Our results suggest a need to more precisely define BCC subtypes. We suggest reporting BCC subtype using a two-tiered risk grouping, followed by specific subtypes present. Further studies examining the inter-rater reliability of less common BCC subtypes are required.

Aberrant p16, p53 and Ki-67 immunohistochemistry staining patterns can distinguish solitary keratoacanthoma from cutaneous squamous cell carcinoma.

Keratoacanthoma (KA) is widely considered a benign, usually self-resolving, neoplasm distinct from cutaneous squamous cell carcinoma (cSCC), while some consider KA to be indistinguishable from cSCC. Published studies indicate utility for p16, p53, Ki-67 immunostaining and elastic van Gieson (EVG) in the assessment of KA and cSCC. We compared clinical features and staining patterns for p16, p53, Ki-67 and EVG in fully excised KA, cSCC with KA-like features (cSCC-KAL) and other cSCC (cSCC-OTHER). Significant differences between KA, cSCC-KAL and cSCC-OTHER were found for head and neck location (20%, 86%, 84%), and duration <5 months (95%, 63%, 36%). KA shows both a mosaic pattern for p16 (>25-90% of neoplasm area) and peripheral graded pattern for p53 (up to 50% moderate and strong nuclear staining) in 92% compared with 0% of cSCC-KAL and 0% of cSCC-OTHER. In contrast, a highly aberrant pattern (usually null) for one or both p16 and p53, was present in 0% of KA, 83.8% of cSCC-KAL and 90.9% of cSCC-OTHER. Abnormal distribution of Ki-67 beyond the peripheral 1-3 cells was uncommon in KA (4.2%) and common in cSCC-KAL (67.6%) and cSCC-OTHER (88.4%). Moderate to striking entrapment of elastic and collagen fibres was present in the majority of KA (84%), cSCC-KAL (81%) and cSCC-OTHER (65%). KA are clinically distinct neoplasms typically of short duration occurring preferentially outside the head and neck and generally lacking aberrations of p16, p53 and Ki-67, compared with cSCC that have high rates of aberrant or highly aberrant p16, p53 and Ki-67, but EVG lacked specificity.

Fibroblast activation protein as a potential theranostic target in brain metastases of diverse solid tumours.

Brain metastases are a very common and serious complication of oncological diseases. Despite the vast progress in multimodality treatment, brain metastases significantly decrease the quality of life and prognosis of patients. Therefore, identifying new targets in the microenvironment of brain metastases is desirable. Fibroblast activation protein (FAP) is a transmembrane serine protease typically expressed in tumour-associated stromal cells. Due to its characteristic presence in the tumour microenvironment, FAP represents an attractive theranostic target in oncology. However, there is little information on FAP expression in brain metastases. In this study, we quantified FAP expression in samples of brain metastases of various primary origin and characterised FAP-expressing cells. We have shown that FAP expression is significantly higher in brain metastases in comparison to non-tumorous brain tissues, both at the protein and enzymatic activity levels. FAP immunopositivity was localised in regions rich in collagen and containing blood vessels. We have further shown that FAP is predominantly confined to stromal cells expressing markers typical of cancer-associated fibroblasts (CAFs). We have also observed FAP immunopositivity on tumour cells in a portion of brain metastases, mainly originating from melanoma, lung, breast, and renal cancer, and sarcoma. There were no significant differences in the quantity of FAP protein, enzymatic activity, and FAP+ stromal cells among brain metastasis samples of various origins, suggesting that there is no association of FAP expression and/or presence of FAP+ stromal cells with the histological type of brain metastases. In summary, we are the first to establish the expression of FAP and characterise FAP-expressing cells in the microenvironment of brain metastases. The frequent upregulation of FAP and its presence on both stromal and tumour cells support the use of FAP as a promising theranostic target in brain metastases.

Blood culture quality assurance: findings from a RCPAQAP Key Incident Monitoring and Management Systems (KIMMS) audit of blood culture performance.

Blood cultures (BC) are the gold standard investigation for bloodstream infection. Standards exist for BC quality assurance, but key quality indicators are seldom measured. The Royal College of Pathologists of Australasia Quality Assurance Programs (RCPAQAP) Key Incident Monitoring and Management Systems (KIMMS) invited laboratories for the first time to participate in an audit to determine adult BC positivity rates, contamination rates, sample fill volumes and the proportion received as a single set. The overall aim of the KIMMS audit was to provide laboratories with a mechanism for peer review and benchmarking. Results from 45 laboratories were analysed. The majority of laboratories (n=28, 62%) reported a positivity rate outside the recommended range of 8-15%. Contamination rates ranged from zero (n=5) to 12.5%, with seven laboratories (15%) reporting a contamination rate greater than the recommended 3%. Fifteen laboratories (33%) reported an average fill volume of less than the recommended 8-10 mL per bottle, with 11 laboratories (24%) reporting fill volumes of 5 mL or less whilst 13 (28%) laboratories were not able to provide any fill volume data. Thirteen laboratories (29%) reported that 50% or more of BC were received as single set, and eight (17%) were not able to report this data. This audit highlights there are deficiencies in BC quality measures across laboratories. To support BC quality improvement efforts, RCPAQAP KIMMS will offer a yearly BC quality assurance audit to encourage laboratories to monitor their BC quality performance.