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AimThe prognostic role of CD274 (programmed cell death ligand 1 (PD-L1)) overexpression has been examined in many studies. However, the results are controversial and conflicting. The present study aims to investigate the potential role of CD274 (PD-L1) immunohistochemical overexpression as a prognostic marker in malignant tumours.MethodsWe searched PubMed, Embase and Web of Science from inception to December 2021 to identify potentially eligible studies. The pooled HRs with 95% CIs were calculated to identify the association between CD274 (PD-L1) overexpression and overall survival (OS), cancer-specific survival, disease-free survival, recurrence-free survival and progression-free survival in 10 lethal malignant tumours. Heterogeneity and publication bias were also analysed.ResultsThe study included 57 322 patients from 250 eligible studies (241 articles). The meta-analysis by tumour type using multivariate HR revealed worse OS in non-small cell lung cancer (HR 1.41, 95% CI 1.19 to 1.68), hepatocellular carcinoma (HR 1.75, 95% CI 1.11 to 2.74), pancreatic cancer (HR 1.84, 95% CI 1.12 to 3.02), renal cell carcinoma (HR 1.55, 95% CI 1.12 to 2.14) and colorectal cancer (HR 1.46, 95% CI 1.14 to 1.88). Estimated HRs showed associations between CD274 (PD-L1) overexpression and worse prognosis across different types of tumours in various survival endpoints, but no inverse correlation was identified. The heterogeneity for most of the pooled results was high.ConclusionsThis large meta-analysis suggests that CD274 (PD-L1) overexpression is a potential biomarker for multiple types of cancers. However, further studies are needed to reduce high heterogeneity.PROSPERO registration numberCRD42022296801.

The objective of the present study was to investigate the association between angiotensin-converting enzyme (ACE) inhibitor use and cancer incidence (overall, and breast, prostate, and colorectal cancers specifically) in a large representative sample of US adults. Cross-sectional data on cancer diagnosis, timing of cancer diagnosis, ACE inhibitor use, and other characteristics were extracted from 49 512 adults aged ≥ 20years participating in the National Health and Nutrition Examination Survey (1999–2016). Multivariable-logistic and propensity score matching (PSM) regressions examined the relationship between pre-diagnosis use of ACE inhibitors and diagnosis of all cancers, and breast, prostate, and colorectal cancers specifically. Overall, we observed an increased likelihood of cancer diagnosis [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.088–1.480] among those who used ACE inhibitors compared to non-ACE inhibitor use, and for prostate cancer diagnosis (OR 1.438, 95% CI 1.090–1.897), after adjusting for age, sex, body mass index, race/ethnicity, educational attainment, physical activity, alcohol drinking status, smoking status, and high blood pressure. PSM regression retrieved more conservative estimates such that the increased likelihood of cancer diagnosis was only observed when comparing ACE inhibitor users with non-drug users (OR 1.022, 95% CI 1.016–1.027). Compared with non-ACE inhibitor use, ACE inhibitor use was associated with an increased risk of prostate cancer. In conclusion, in this large representative sample of US adults, it was found that ACE inhibitor use may have a marginal influence on some cancers. © 2020, Springer Nature Switzerland AG.

Ki-67 assessment is a key step in the diagnosis of neuroendocrine neoplasms (NENs) from all anatomic locations. Several challenges exist related to quantifying the Ki-67 proliferation index due to lack of method standardization and inter-reader variability. The application of digital pathology coupled with machine learning has been shown to be highly accurate and reproducible for the evaluation of Ki-67 in NENs. We systematically reviewed all published studies on the subject of Ki-67 assessment in pancreatic NENs (PanNENs) employing digital image analysis (DIA). The most common advantages of DIA were improvement in the standardization and reliability of Ki-67 evaluation, as well as its speed and practicality, compared to the current gold standard approach of manual counts from captured images, which is cumbersome and time consuming. The main limitations were attributed to higher costs, lack of widespread availability (as of yet), operator qualification and training issues (if it is not done by pathologists), and most importantly, the drawback of image algorithms counting contaminating non-neoplastic cells and other signals like hemosiderin. However, solutions are rapidly developing for all of these challenging issues. A comparative meta-analysis for DIA versus manual counting shows very high concordance (global coefficient of concordance: 0.94, 95% CI: 0.83–0.98) between these two modalities. These findings support the widespread adoption of validated DIA methods for Ki-67 assessment in PanNENs, provided that measures are in place to ensure counting of only tumor cells either by software modifications or education of non-pathologist operators, as well as selection of standard regions of interest for analysis. NENs, being cellular and monotonous neoplasms, are naturally more amenable to Ki-67 assessment. However, lessons of this review may be applicable to other neoplasms where proliferation activity has become an integral part of theranostic evaluation including breast, brain, and hematolymphoid neoplasms. © 2022, The Author(s).

Summary Hepatoid tumors (HT) are rare neoplasms morphologically resembling hepatocellular carcinoma, which arise in several organs other than the liver. A comprehensive molecular profile of this group of neoplasms is still lacking. Genomic characterization of 19 HTs from different organs (three colon HTs, four esophagogastric HTs, four biliary HTs, six genitourinary HTs, two lung HTs) was performed using a multigene next-generation sequencing panel. NGS unraveled a composite molecular profile of HT. Their genetic alterations were clearly clustered by tumor site: (i) colorectal HT displayed microsatellite instability, high tumor mutational burden, mutations in ARID1A/B genes and NCOA4-RET gene fusion (2/3 cases); (ii) gastric HT had TP53 mutations (2/4); (iii) biliary HT displayed loss of CDKN2A (3/4) and loss of chromosome 18 (2/4); (iv) genital HT showed gain of chromosome 12 (3/6); (v) lung HT had STK11 somatic mutations (2/2). The only commonly mutated gene occurring in HT of different sites was TP53 (8/19 cases: colon 2, esophagogastric 2, biliary 2, genital 1, lungs 1). This study shows that most genetic alterations of HT were clustered by site, indicating that context matters. The novel potential targets for HT precision oncology are also clustered based on the anatomic origin. This study shed light on the biology of these rare cancers and may have important consequences for treatment decisions and clinical trial selection for HT patients.