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There is a paucity of population‐based data detailing the incidence and survival of patients with soft tissue sarcoma (STS), in part due to the heterogeneity of disease and changes to classification. Here, the incidence and survival of all STS subtypes registered in England between 2013 and 2017 were analysed using cancer registry data held by the National Cancer Registration and Analysis Service. Age‐standardised incidence rates were calculated per 1 000 000 using the 2013 European Standard Population. Net survival was computed using Brenner's alternative method, with the Ederer II estimator. Age‐specific overall survival was assessed using Kaplan‐Meier. The influence of age, sex, socioeconomic deprivation and diagnostic routes on survival was assessed using Cox proportional hazards modelling. In total, 19 717 patients were diagnosed with STS, an average of 3943 patients per year and representing approximately 0.8% of malignancies. The most common histological diagnoses were Gastrointestinal Stromal Tumours (GIST), leiomyosarcoma and undifferentiated sarcoma, accounting for 20.2%, 13.3% and 12.7% of all sarcomas, respectively. Five‐year net survival for all malignant STS was 65.0%; and was lowest for patients with vascular tumours at 39%. Patients from most deprived cohorts had 23% greater chance of dying within 5 years than patients in least deprived areas. This population‐based study has allowed us for the first time to define the incidence and survival rates of prevalent STS subtypes in England such as GIST, liposarcoma and leiomyosarcoma, as well as rare entities and groups with inferior outcome. This data is invaluable for service provision, benchmarking and addressing inequality. [ABSTRACT FROM AUTHOR]

The International Federation of Gynaecology and Obstetrics (FIGO) updated its staging system for endometrial cancer in June 2023. The new system includes nonanatomic histological parameters and molecular classification, which are not traditionally part of staging systems. In August 2023, a survey was conducted among pathologists and clinicians to determine their views on adopting the FIGO 2023 system in the UK. The results showed no consensus on whether to incorporate the new parameters into staging, and only 34% of respondents favored adopting FIGO 2023. Access to timely molecular testing was identified as a factor that correlated with support for adoption. The British Association of Gynaecological Pathologists (BAGP) and British Gynaecological Cancer Society (BGCS) currently do not recommend adopting FIGO 2023 in the UK due to controversies and limited access to molecular classification. [Extracted from the article]

Summary: This analysis is the largest population‐based study to date to provide contemporary and comprehensive epidemiological estimates of all third edition of the International Classification of Diseases for Oncology (ICD‐O‐3) coded Langerhans cell histiocytosis (LCH) from England. People of all ages were identified from the National Cancer Registration Dataset using ICD‐O‐3 morphologies 9751–9754 for neoplasms diagnosed in 2013–2019. A total of 658 patients were identified, of whom 324 (49%) were children aged <15 years. The age‐standardised incidence rate was 4.46 (95% confidence interval [CI] 3.99–4.98) per million children and 1.06 (95% CI 0.94–1.18) per million adults aged ≥15 years. Prevalence of LCH was 9.95 (95% CI 9.14–10.81) per million persons at the end of 2019. The 1‐year overall survival (OS) was 99% (95% CI 97%–100%) for children and 90% (95% CI 87%–93%) for adults. Those aged ≥60 years had poorer OS than those aged <15 years (hazard ratio [HR] 22.12, 95% CI 7.10–68.94; p < 0.001). People in deprived areas had lower OS than those in the least deprived areas (HR 5.36, 95% CI 1.16–24.87; p = 0.03). There will inevitably be other environmental factors and associations yet to be identified, and the continued standardised data collection will allow further evaluation of data over time. This will be increasingly important with developments in LCH management following the large collaborative international trials such as LCH IV. [ABSTRACT FROM AUTHOR]

Gaps in the translation of research findings to clinical management have been recognized for decades. They exist for the diagnosis as well as the management of cancer. The international standards for cancer diagnosis are contained within the World Health Organization (WHO) Classification of Tumours, published by the International Agency for Research on Cancer (IARC) and known worldwide as the WHO Blue Books. In addition to their relevance to individual patients, these volumes provide a valuable contribution to cancer research and surveillance, fulfilling an important role in scientific evidence synthesis and international standard setting. However, the multidimensional nature of cancer classification, the way in which the WHO Classification of Tumours is constructed, and the scientific information overload in the field pose important challenges for the translation of research findings to tumour classification and hence cancer diagnosis. To help address these challenges, we have established the International Collaboration for Cancer Classification and Research (IC3R) to provide a forum for the coordination of efforts in evidence generation, standard setting and best practice recommendations in the field of tumour classification. The first IC3R meeting, held in Lyon, France, in February 2019, gathered representatives of major institutions involved in tumour classification and related fields to identify and discuss translational challenges in data comparability, standard setting, quality management, evidence evaluation and copyright, as well as to develop a collaborative plan for addressing these challenges. What's new? The World Health Organization Classification of Tumours has been informing cancer research and clinical practice by providing an international consensus on the tumour criteria for cancer diagnosis. In a new initiative coordinated by the International Agency for Research on Cancer, major institutions are now joining forces to address the remaining challenges in translational research and facilitate the application of research results to clinical practice. The newly‐established International Collaboration for Cancer Classification and Research (IC3R) aims to provide a forum for the coordination of efforts in generating evidence, setting standards, and providing best practice recommendations for tumor classification and cancer research. [ABSTRACT FROM AUTHOR]

TP53 mutations are considered a surrogate biomarker of the serous‐like 'copy number high' molecular subtype of endometrial carcinoma (EC). In ovarian carcinoma, p53 immunohistochemistry (IHC) accurately reflects mutational status with almost 100% specificity but its performance in EC has not been established. This study tested whether p53 IHC reliably predicts TP53 mutations identified by next‐generation sequencing (NGS) in EC biopsy samples for all ECs and as part of a molecular classification algorithm after exclusion of cases harbouring mismatch repair defects (MMRd) or pathogenic DNA polymerase epsilon exonuclease domain mutations (POLEmut). A secondary aim assessed inter‐laboratory variability in p53 IHC. From a total of 207 cases from five centres (37–49 cases per centre), p53 IHC carried out at a central reference laboratory was compared with local IHC (n = 164) and curated tagged‐amplicon NGS TP53 sequencing results (n = 177). Following consensus review, local and central p53 IHC results were concordant in 156/164 (95.1%) tumours. Discordant results were attributable to both interpretive and technical differences in staining between the local and central laboratories. When results were considered as any mutant pattern versus wild‐type pattern staining, however, there was disagreement between local and central review in only one case. The concordance between p53 IHC and TP53 mutation was 155/168 (92.3%) overall, and 117/123 (95.1%) after excluding MMRd and POLEmut EC. Three (3/6) discordant results were in serous carcinomas with complete absence of p53 staining but no detectable TP53 mutation. Subclonal mutant p53 IHC expression was observed in 9/177 (5.1%) cases, of which four were either MMRd or POLEmut. Mutant pattern p53 IHC was observed in 63/63 (100%) serous carcinomas that were MMR‐proficient/POLE exonuclease domain wild‐type. Optimised p53 IHC performs well as a surrogate test for TP53 mutation in EC biopsies, demonstrates excellent inter‐laboratory reproducibility, and has high clinical utility for molecular classification algorithms in EC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: To quantify geographic variation in the use of lymphadenectomy and/or external-beam radiotherapy (EBRT) for endometrial cancer in England.Design: Cross-sectional analysis of population-based data.Setting: English cancer registry data, linked to chemotherapy, radiotherapy and hospital episodes statistics data.Population: Twenty-two thousand four hundred and eighty-three women with endometrial cancer presenting without clinical or radiological evidence of distant metastatic spread, diagnosed in England from 2013 to 2016.Methods: Proportions of patients receiving lymphadenectomy and/or EBRT were compared across 19 Cancer Alliances, to identify variations in clinical practice. Two separate logistic regression models assessed the impact on variation of adjustment for tumour and patient characteristics.Main Outcome Measures: Receipt of lymphadenectomy, receipt of EBRT.Results: There was substantial variation by Cancer Alliance in the adjusted proportion of women with endometrial cancer receiving lymphadenectomy (range 5% [95% CI 4-6%] to 48% [95% CI 45-52%]) and EBRT (range 10% [95% CI 7-12%] to 31% [95% CI 28-33%]), after adjusting for variation in pathological grade, age, comorbidities, deprivation, ethnic group and (EBRT only) FIGO stage. Different approaches to clinical practice were identified; (i) one Cancer Alliance had significantly higher than average lymphadenectomy and significantly lower than average EBRT use, (ii) three had high use of both lymphadenectomy and EBRT, (iii) one had low lymphadenectomy use and high EBRT use, and (iv) three had low use of both lymphadenectomy and EBRT.Conclusions: Lymphadenectomy is probably used to triage for EBRT when lymphadenectomy use is high and EBRT use is low. This is probably a result of variation in local endometrial cancer management guidelines, suggesting that UK recommendations should be clarified.Tweetable Abstract: There is geographic variation in England in the use of lymphadenectomy and radiotherapy to treat endometrial cancer. [ABSTRACT FROM AUTHOR]

The author comments on TNM clinical staging of prostate cancer. Topics discussed include Clinical staging is important in assessing the spread of prostate cancer because a final pathological stage would be available only in those patients who undergo radical prostatectomy; issue within the TNM system related to the sub-categorization of cT2 prostate cancer by magnetic resonance imaging; and difference between the Union for International Cancer Control and American Joint Committee on Cancer.

The adaptor protein complex AP-3 is involved in the sorting of lysosomal membrane proteins to late endosomes/lysosomes. It is unclear whether AP-3-containing vesicles form at thetrans-Golgi network (TGN) or early endosomes. We have compared the trafficking routes of endolyn/CD164 and‘typical’ lysosomal membrane glycoproteins (lgp120/lamp-1 and CD63/lamp-3) containing cytosolic YXXΦ-targeting motifs preceded by asparagine and glycine, respectively. Endolyn, which has a NYHTL-motif, is concentrated in lysosomes, but also occurs in endosomes and at the cell surface. We observed predominant interaction of the NYHTL-motif with theμ-subunits of AP-3 in the yeast two-hybrid system. Endolyn was mislocalized to the cell surface in AP-3-deficientpearlcells, confirming a major role of AP-3 in endolyn traffic. However, lysosomal delivery of endolyn (or a NYHTL-reporter), but not GYXXΦ-containing proteins, was practically abolished when AP-2-mediated endocytosis or traffic from early to late endosomes was inhibited in NRK and 3T3 cells. This indicates that endolyn is mostly transported along the indirect lysosomal pathway (via the cell surface), rather than directly from the TGN to late endosomes/lysosomes. Our results suggest that AP-3 mediates lysosomal sorting of some membrane proteins in early endosomes in addition to sorting of proteins with intrinsically strong AP-3-interacting lysosomal targeting motifs at the TGN. [ABSTRACT FROM AUTHOR]