Search

Our previous study reported that clinical features, including the lateral/ventral tongue and non-homogeneous lesions, were associated with increased risk of malignant changes in cytological samples from oral potentially malignant disorders (OPMDs). This cross-sectional study aimed to evaluate the frequency and risk of DNA aneuploidy in the series of 748 patients with OPMD. The cut-off value of aneuploidy was defined as DNA index ≥3.5. We found that the frequency of DNA aneuploidy was higher in OPMD patients >60 years old, and in those with lateral/ventral tongue sites, non-homogeneous lesions, and high-grade dysplasia, than in control group (P 60 years old (1.69-fold; P = 0.022), in those with lateral/ventral tongue sites (2.35-fold; P

Our previous study reported that clinical features, including the lateral/ventral tongue and non-homogeneous lesions, were associated with increased risk of malignant changes in cytological samples from oral potentially malignant disorders (OPMDs). This cross-sectional study aimed to evaluate the frequency and risk of DNA aneuploidy in the series of 748 patients with OPMD. The cut-off value of aneuploidy was defined as DNA index ≥3.5. We found that the frequency of DNA aneuploidy was higher in OPMD patients >60 years old, and in those with lateral/ventral tongue sites, non-homogeneous lesions, and high-grade dysplasia, than in control group (P < 0.01). Consistently, the risk of aneuploidy occurrence was higher in patients >60 years old (1.69-fold; P = 0.022), in those with lateral/ventral tongue sites (2.35-fold; P < 0.001), and in those with high-grade dysplasia (3.19-fold; P < 0.001). Collectively, increased frequency and risk of DNA aneuploidy occurred in OPMD patients aged over 60 years with high-grade dysplasia located at the lateral/ventral tongue. These patients should be required to intensive management and follow-up. [ABSTRACT FROM AUTHOR]

Abstract Background Current evidence on diagnostic value of aneuploidy with DNA image cytometry (ICM) using brushings for oral potentially malignant disorders (OPMD) is limited by sample size and inconsistent classification criteria of aneuploidy. This study aimed to explore the optimal cut‐off values of DNA content and evaluate the diagnostic accuracy of DNA‐ICM for detecting dysplasia and/or carcinoma in OPMD. Materials and Methods A total of 401 consecutive patients with OPMD were enrolled in this prospective diagnostic study. Brushing and biopsy sample form each patient was processed by DNA‐ICM and histological examination respectively. Results When the optimal cut‐off of at least one aneuploid cell with DNA index (DI) ≥2.3, the area under the curves (AUC) was 0.735 and positive predictive value was 92.7% for detecting dysplasia within OPMD. When the optimal cut‐off of at least one aneuploid cell with DI ≥ 3.5, the AUC was 0.851 and negative predictive values was 96.8% for detecting carcinoma within OPMD. Importantly, multivariate analysis revealed that aneuploidy with DI ≥ 2.3 in OPMD was significantly associated with dysplasia risk (adjusted OR, 5.52; 95%CI, 2.90‐10.51; P

Aim: In breast carcinoma (BC), the relationship between the ploidy pattern and molecular subtyping is still unknown. We aim to investigate the prognostic impact of DNA ploidy within molecular subtypes of a large cohort of BC patients., Methods: The series involved 520 BC patients with no neoadjuvant therapy and a median follow-up of 115.5 months. Immunohistochemical assessment of hormonal receptors, ERBB2 (HER2) status and Ki67 proliferative activity was the basis of the surrogate molecular subtyping. Ploidy was evaluated by DNA flow cytometry in fresh/frozen tumour samples. Kaplan-Meier (K-M) survival estimation was used for prognostic statistical analysis., Results: Luminal A subtype had the lowest prevalence of disease recurrences (23.6 %) and deaths from disease (18.3 %), while Luminal B (42.2 %/37.9 %), Triple-negative (46.4 %/40.6 %), and HER2-positive (55.9 %/50.0 %) subtypes had the highest. The Triple-positive subtype shows an intermediate/low frequency of adverse events (29.4 % of disease recurrences and 17.6 % of deaths from disease). Luminal A tumours were mostly diploid (55.3 %), while Triple-negative and HER2-positive tumours showed a high incidence of aneuploidy (82.6 % and 88.2 %, respectively). Luminal B and Triple-positive tumours had an intermediate percentage of aneuploidy (63.8 % and 70.6 %, respectively). K-M survival curves showed that DNA aneuploidy is significantly associated with shorter disease-free survival and overall survival in Luminal A and Luminal B molecular subtypes., Conclusion: DNA aneuploidy identifies a subset of Luminal BC patients with worse clinical outcome, potentially eligible for more aggressive adjuvant therapy., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Oral leukoplakia (OLK) is one of the most common potentially malignant disorders. High-risk lesions require early intervention before developing into oral cancer. Photodynamic therapy (PDT) is a noninvasive technique for premalignant lesions. Scalpel biopsy remains a reliable method for monitoring the prognosis of OLK, but it is an invasive procedure with poor reproducibility to suspicious lesions. DNA aneuploidy cytology by oral cytobrush has been proposed as a promising objective and noninvasive tool in screening and diagnosing premalignant and malignant lesions. Here, we discussed the significance of artificial intelligence (AI)-assisted DNA aneuploidy cytology by image cytometry (DNA-ICM) for surveilling non-homogeneous OLK with moderate-to-severe dysplasia that was treated by 5-aminolevulinic acid-mediated PDT (ALA-PDT). The present study provides a scheme of the sequential management and surveillance strategy for OLK., Competing Interests: Declaration of Competing Interest There are no conflicts of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Abstract Background DNA aneuploidy has attracted growing interest in clinical practice. Nevertheless, its prognostic value in gastric cancer patients remains controversial. This meta-analysis aims to explore the impact of DNA ploidy status on the survival of gastric cancer patients. Methods We used PubMed and Web of Science databases to retrieve relevant articles. The correlation between DNA aneuploidy and the clinicopathological features of gastric cancer, such as stage, depth of invasion (T), lymph node metastasis (N), distant metastasis (M), differentiation (G), tumor types (Lauren classification) and overall survival (OS) were evaluated. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) were collected carefully from each article OS was presented with HRs. The relationships between DNA aneuploidy and each characteristic were analyzed using risk ratios (RR) and a 95% confidence interval (CI). Significance was established using P

Objective: To explore the diagnostic value of DNA aneuploidy analysis combined with radial endobronchial ultrasound (R-EBUS)-guided transbronchial biopsy in peripheral lung lesions., Method: We performed a retrospective analysis of patients who underwent R-EBUS examination. DNA aneuploidy analysis of bronchial washing from the target bronchial segment were performed. The clinical information, R-EBUS data, pathological results and DNA image cytometry (DNA-ICM) results were collected. For patients who did not have a clear diagnosis after bronchoscopy, follow-up data was recorded., Results: A total of 42 cases were included. Thirty patients had confirmed malignant tumor of the lung, 19 of which were confirmed by pathology after bronchoscopy, and 11 cases were confirmed later by surgery or percutaneous lung puncture. Twelve patients were finally considered to have benign lesions. The sensitivity of R-EBUS is 63.3% and the specificity is 100%. DNA-ICM has a sensitivity of 76.7% and a specificity of 91.7%. When combined, they have a sensitivity of 90%, and specificity 91.7%. As for malignant lesions, we further analyzed smoking, the size and location of lesions on chest CT, the number of aneuploid cells and the maximum value of DNA content. The results indicated that increased number of aneuploid cells or increased max value of DNA content may predict higher probability of malignancy., Conclusion: DNA-ICM combined with R-EBUS can improve the diagnostic sensitivity of malignant peripheral lung lesions. Increased number of aneuploid cells or increased max value of DNA content may indicate that the lesions are more likely to be malignant., (© 2022 The Authors. Diagnostic Cytopathology published by Wiley Periodicals LLC.)

• Of the 18 canine malignant tumor cell lines examined, 15 showed aneuploidy. • Of the 15 aneuploid cell lines, 5 showed centrosome amplification (CA). • DNA aneuploidy in canine tumor cells might be partly due to CA. DNA aneuploidy, the altered DNA content of a cell, is a common feature of canine tumors. However, it is unclear whether aneuploid DNA in canine tumor cells show centrosome amplification (CA), which contributes to numerical and structural chromosome aberrations that result in DNA aneuploidy. Here, we evaluated whether DNA aneuploidy and CA occur concurrently in canine tumor cell lines. Centrosome numbers were evaluated in 18 canine tumor cell lines by immunocytochemistry with anti-γ-tubulin antibody, and DNA content was evaluated by flow cytometry using propidium iodide. A total of 15 cell lines showed DNA aneuploidy, and CA was observed in 5 of these 15 cell lines. Together, our results suggest that DNA aneuploidy in canine tumor cells might be explained at least in part by CA. In addition, cell lines with CA may be useful tools to examine the detailed relationship between CA and DNA aneuploidy and the molecular mechanism of CA in canine tumor. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the relationship between tobacco smoke habit, patient age, DNA aneuploidy and genomic DNA copy number aberrations (CNAs) in oral potentially malignant disorder (OPMD) and oral squamous cell carcinoma (OSCC) patients. DNA aneuploidy was detected by high-resolution DNA flow cytometry (hr DNA-FCM) on DAPI stained nuclei obtained from multiple tissue samples from OPMDs/OSCCs in 220 consecutive patients. Nuclear genomic aberrations were determined in a subset of 65 patients by genome-wide array comparative genomic hybridization (aCGH) using DNA extracted from either diploid or aneuploid nuclei suspension sorted by FCM. DNA aneuploidy and mean nuclear genomic aberrations were associated with patients' age. In particular, DNA aneuploidy strongly associated with age in non-smoker OPMDs/OSCCs patients. OSCCs from smokers showed a lower prevalence of DNA aneuploidy compared to OSCCs from non-smokers. A higher occurrence of DNA aneuploidy (particularly in smokers' OPMDs) was observed in patients characterized by involvement of a single oral subsite. Our study suggests that: 1) DNA aneuploidy in non-smokers is mainly related to aging; 2) OPMDs/OSCCs involving multiple oral subsites in smokers are less likely to develop DNA aneuploidy compared to non-smokers; 3) OSCC development is characterized by both CIN and CIN-independent mechanisms and that the latter are more relevant in smokers. This study provides evidence that DNA diploid OPMDs may be considered at lower risk of cancerization than DNA aneuploid ones in non-smokers but not in smokers.

DNA aneuploidy is a cancer biomarker, which may have a potential diagnostic value in body effusion specimen. DNA aneuploidy is determined by measuring the DNA content of tested cells and comparing them with diploid cells (2c). In order to assess the value of automated DNA image cytometry (DNA-ICM) in the cytologic diagnosis of effusion, we measured DNA ploidy using an automated DNA-ICM analysis system in 126 consecutive effusion specimens and followed the cases for histologic diagnosis. Half of each effusion specimen was used to prepare cytologic smears for conventional cytologic diagnosis, while the other half was used to prepare a monolayer slide stained by Feulgen stain for automated ICM. By using Youden index, we found that 4 cells exceeding 2.5c is the optimal cut off value for aneuploidy, which has a sensitivity of 88.3% and specificity of 100% for diagnosis of malignant effusion. We also found that the DNA aneuploidy thresholds used for other types of cytologic specimens cannot be used in the diagnosis of effusion specimens. Our study demonstrated that automated DNA image cytometry is a simple, practical and cost-effective method for adjunct diagnosis of malignant effusion.

Subjectivity in oral dysplasia grading has prompted evaluation of molecular‑based tests to predict malignant transformation. Aneuploidy detected by DNA image‑based cytometry (ICM) is currently the best predictor but fails to detect certain high risk lesions. A novel multiplex fluorescence in situ hybridization (FISH) panel was used to explore possible explanations by detecting aneuploidy at the single cell level. FISH was compared to reference standard DNA ICM in 19 oral lesions with epithelial dysplasia and used to characterize the cellular architecture. Copy number variation at 3q28, 7p11.2, 8q24.3, 11q13.3 and 20q13.12 and matched chromosome specific loci were assessed by dual‑color FISH to assess numerical and spatial patterns of copy number increase and gene amplification. FISH revealed wide variation in copy number at different loci. Only low level copy number gain was present and often in only a small proportion of cells, although usually with all or all but one locus (9/12). Four cases showed gene amplification, one at two loci. Some probes revealed an internal presumed clonal structure within lesions not apparent in routine histological examination. Both methods produced similar diagnostic results with concordance in detection of aneuploidy by both methods in 17 out of 19 samples (89%). We have shown that oral dysplastic lesions may contain very few aneuploid cells at a cellular level, high copy number gain is rare and changes appear to arise from large chromosomal fragment duplications. Single stem lines are relatively homogeneous for loci with copy number gain but there is a subclonal structure revealed by gene amplification in some lesions.

DNA aneuploidy is of interest as an additive marker for carcinoma risk in ulcerative colitis. It is known that colorectal carcinomas often are aneuploid with DNA indices centered around a median value of 1.5, corresponding to triploidy, and that adenomas, if aneuploid, have DNA indices closer to 2.0, the tetraploid region. In a colonoscopic surveillance programme, colorectal mucosal biopsies from 104 patients with ulcerative colitis were examined by flow cytometry, and the DNA indices determined and compared with findings of cellular dysplasia. In 17 patients, DNA aneuploidy was diagnosed, with DNA indices ranging from 1.2 to 2.0, median 1.9. Three patients with high grade dysplasia all had DNA indices within the triploid region. These results were compared with the DNA indices from a group of 49 patients with non‐colitis‐associated aneuploid colorectal carcinomas, in which the levels ranged from 1.1 to 2.0 with a median value of 1.5. Accordingly, the DNA index in the colitis patients with aneuploidy was more often within the tetraploid region. These results, obtained in patients with ulcerative colitis, indicate a possible precancerous progress from diploidy over tetraploidy to triploidy also in patients with long‐standing ulcerative colitis. In addition, the results speak in favour of a connection between DNA indices in the triploid region and more profound premalignant alterations.

Introduction: aneuploidy has been observed in 6-27% of lesions known to be precursors of colorectal cancer, such as adenomas or ulcerative colitis. It has been suggested that aneuploidy may predispose to malignancy in these cases. However, its role in the adenoma-carcinoma sequence has not been definitely established. The objective of this study was to assess the incidence of aneuploidy in colon adenomas, as well as to study its possible role in the adenoma-carcinoma sequence. Material and methods: the study was performed on a series of 57 large bowel adenomas measuring 10 mm or more, collected from 54 consecutive patients. All specimens were obtained either by endoscopic or by surgical resection. There were 49 adenomas with low-grade dysplasia, two with high-grade dysplasia, two intramucous carcinomas, and four microinvasive carcinomas. A flow cytometric DNA analysis was performed in fresh specimens following Vindelov´s method. Results: aneuploid DNA was detected in five out of 49 low-grade dysplasia adenomas (10%), in all four high-grade dysplasia adenomas or intramucous carcinomas (100%), and in three out of four microinvasive carcinomas (75%). The association between aneuploidy and high-grade dysplasia adenomas, intramucous, or microinvasive carcinoma was statistically significant (p < 0.001). No association was found between aneuploidy and any of the following features: age, gender, clinical symptoms of patients, and size or location of adenomas. Conclusions: the incidence of aneuploidy in this series was 10% in low-grade dysplasia adenomas, and 87% in high-grade dysplasia adenomas or carcinomas, and this difference was statistically significant. These findings suggest that aneuploidy may play a role in the adenoma-carcinoma sequence.Introducción: en patología benigna de intestino grueso precursora del cáncer colorrectal, como adenomas o colitis ulcerosa, se ha observado aneuploidía en el 6-27% de los casos y se ha sugerido que su presencia predispone al desarrollo de malignidad. Sin embargo, su papel en la secuencia adenoma-carcinoma no se ha demostrado de forma concluyente. El objetivo de nuestro trabajo fue valorar la incidencia de aneuploidía en adenomas colónicos, con y sin signos de malignidad, y estudiar su posible papel en la secuencia adenoma-carcinoma. Material y métodos: el estudio se realizó en una serie de 57 adenomas de intestino grueso, de 10 o más milímetros, recogidos de forma consecutiva de 54 pacientes. Las piezas se obtuvieron en todos los casos mediante resección endoscópica o quirúrgica. En 49 casos se trataba de adenomas con displasia de bajo grado, en dos casos de adenomas con displasia de alto grado, dos adenocarcinomas intramucosos y en otros cuatro de adenocarcinomas microinvasivos. El estudio del ADN se realizó en la pieza operatoria en fresco mediante citometría de flujo utilizado el método de Vindelov. Resultados: se detectó ADN aneuploide en cinco de los 49 adenomas con displasia de bajo grado (10%), en los cuatro adenomas con displasia de alto grado o adenocarcinomas intramucosos (100%) y en tres de los cuatro adenocarcinomas microinvasivos (75%). Se observó asociación significativa entre el hallazgos de aneuploidía y displasia de alto grado, adenocarcinoma intramucoso o microinvasivo (p < 0,001). No se apreció asociación entre la existencia de aneuploidía y la edad de los pacientes, sexo, sintomatología clínica, tamaño ni localización de los adenomas. Conclusiones: en adenomas colónicos la incidencia de aneuploidía fue del 10% cuando se trataba de adenomas con displasia de bajo grado y del 87% cuando presentaban displasia de alto grado o adenocarcinoma siendo la diferencia estadísticamente significativa. Estos hallazgos sugieren que la aneuploidía juega un papel en la secuencia adenoma-carcinoma.