Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens

Matsuda, Yoko; Suzuki, Akemi; Esaka, Shikine; Hamashima, Yuri; Imaizumi, Munehisa; Kinoshita, M.; Shirahata, Hiroto; Kiso, Yuri; Kojima, Hiroya; Matsukawa, Miho; Fujii, Yuko; Ishikawa, Naoshi; Aida, Junko; Takubo, Kaiyo; Ishiwata, Toshiyuki; Nishimura, Makoto; Arai, Tomio

doi:10.1111/cyt.12535

Cited by 4 publications

(9 citation statements)

References 25 publications

(67 reference statements)

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“…). Estimation of telomere length in cells obtained by biopsy or in pancreatic juice samples may help in the diagnosis and risk assessment of PDAC …”

Section: Age‐related Neoplastic Changes In the Pancreasmentioning

confidence: 99%

Age‐related morphological changes in the pancreas and their association with pancreatic carcinogenesis

Matsuda

2019

Pathology International

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Age-related pathological changes in the pancreas have been unclear because they are often minor and nonspecific. However, recent studies have shown that they are closely related to various pathological conditions such as pancreatic cancer and diabetes mellitus. Knowledge of age-related changes is important to determine appropriate prevention, detection, and treatment strategies for various diseases observed in elderly patients. We present a review of the pathological age-related non-neoplastic changes in the exocrine pancreas such as pancreatic fatty replacement, lobulocentric pancreatic atrophy, pancreatic duct ectasia, and metaplasia of exocrine pancreas, as well as changes in islet cells. We have discussed common pancreatic neoplasms in elderly patients, such as pancreatic intraepithelial neoplasia (PanIN), intraductal papillary mucinous neoplasms (IPMNs), and pancreatic ductal adenocarcinoma (PDAC). Age-related pathological changes play a key role in pancreatic carcinogenesis via telomere dysfunction. Further studies are warranted to clarify molecular mechanisms of pancreatic carcinogenesis in elderly patients. K E Y W O R D S aging, autopsy, carcinogenesis, pancreas, telomere

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“…). Estimation of telomere length in cells obtained by biopsy or in pancreatic juice samples may help in the diagnosis and risk assessment of PDAC …”

Section: Age‐related Neoplastic Changes In the Pancreasmentioning

confidence: 99%

Age‐related morphological changes in the pancreas and their association with pancreatic carcinogenesis

Matsuda

2019

Pathology International

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“…Clinically, if a sufficient number and quality of cells can be obtained, the method described here would be useful. Cytological specimens are usually suitable for FISH analysis 32 . Compared with tissue specimens, the fixation time needed for cytology specimens is shorter, and the entire cell apparatus is visible 32 .…”

Section: Discussionmentioning

confidence: 99%

“…Because analysis of deletion, fusion, and amplification using FISH requires certain skills and observer experience, we use automated software to detect signal intensities of telomeres, centromeres, and DAPI. Therefore, the method described is not hindered by interobserver differences 32 …”

Section: Discussionmentioning

confidence: 99%

“…Our group has shown that telomere length determined by the Q-FISH method distinguishes malignant and benign cells in cytological specimens of the pancreas obtained by EUS-fine-needle aspiration (FNA). 32 The 2017 revised Fukuoka guidelines proposed using a cyst size greater than 3 cm as a worrisome feature to recommend performing EUS-FNA. 2 The 2015 American Gastroenterological Association guidelines proposed cyst size greater than 3 cm as one of 3 high-risk features, along with dilation of the main pancreatic duct and the presence of a mass or nodule, which should prompt an EUS-FNA, but only if 2 of these features are present simultaneously.…”

Section: Discussionmentioning

confidence: 99%

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Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging

Miki¹,

Matsuda

Aida

et al. 2022

Pancreas

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Objectives: It is challenging to preoperatively distinguish malignant and benign forms of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. The aims of this study were to investigate whether telomere length is associated with pathological grade of IPMNs and age and to clarify the utility of telomere length as a marker to identify malignant IPMNs.Methods: Pancreas tissue was obtained from 28 patients after resection.We measured the telomere lengths of tumor cells in IPMNs and normal duct cells by quantitative fluorescence in situ hybridization. The association of normalized telomere-centromere ratio (NTCR) to pathological grade of IPMNs and age were determined. Results:The NTCR showed a gradual decrease with increasing pathological grade of IPMNs. The NTCR in intermediate-and high-grade dysplasia and adenocarcinoma lesions was significantly shorter than in normal pancreatic ducts (P < 0.05). In multivariate analysis, telomere length was most associated with carcinogenesis. When the cutoff value of NTCR was set to 0.74, the sensitivity for detection of high-grade dysplasia and adenocarcinoma was 82.8%, with a specificity of 87.5%. Conclusions:Telomere shortening occurs with carcinogenesis and aging. A significant reduction of telomere length in IPMNs may be useful for surgical decision making.

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“…The liquid component was used for cytological diagnosis, and the filamentous or solid component for tissue diagnosis. Papanicolaou staining for smear specimens was routinely performed 23,24 . For tissue diagnosis, the tissues were fixed in formalin overnight, routinely processed for paraffin embedding, and sliced into 3‐μm thick sections for haematoxylin‐eosin (HE) staining.…”

Section: Methodsmentioning

confidence: 99%

Cytological scoring for pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration

et al. 2021

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Objective Cytological diagnosis of pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration (EUS‐FNA) is often challenging because of the small sample size or well‐differentiated adenocarcinoma with weak cytological atypia. Therefore, the sensitivity and specificity of cytological diagnosis for pancreatic cancer should be improved. Hence, we aimed to clarify the utility of cytological scoring to distinguish malignant from benign lesions for cytological diagnosis of pancreatic EUS‐FNA specimens. Methods Seven reviewers, including four cytotechnologists and three medical doctors, evaluated 20 morphological indices in pancreatic specimens obtained by EUS‐FNA (malignant, n = 111; benign, n = 31). Statistical analyses were performed using Fisher's exact test, logistic regression analysis, the area under the receiver operating characteristic curve, and Youden index. Results Among the 20 indices, there was a high incidence rate (>40%) of the following 13 indices in malignant cases: irregular structure, hyperchromatic nucleus, irregular cell polarity, unclear cell boundaries, nuclear membrane thickening, anisonucleosis, overlapping, irregular nuclei, high nuclear‐cytoplasmic ratio, binding decline, the simultaneous appearance of malignant and benign cells, enlarged nucleoli, and background necrosis. When we diagnosed pancreatic specimens using these 13 cytological indices, the cut‐off value of 8/9 showed the highest Youden index (0.950) as well as high sensitivity and specificity in distinguishing malignant from benign specimens (98% and 97%, respectively). Conclusion Thirteen cytological indices showed high sensitivity and specificity in differentiating malignant and benign lesions using pancreatic EUS‐FNA samples. All 13 indices were important for diagnosing malignancy in the pancreatic cytology smear of EUS‐FNA. Further validation studies are required.

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Telomere length determined by the fluorescence in situ hybridisation distinguishes malignant and benign cells in cytological specimens

Abstract: The present study revealed that telomere length can be used as an indicator to distinguish malignant and benign cells in cytological specimens. This novel approach may help improve diagnosis for cancer patients.

Cited by 4 publications

References 25 publications

Age‐related morphological changes in the pancreas and their association with pancreatic carcinogenesis

Age‐related morphological changes in the pancreas and their association with pancreatic carcinogenesis

Telomere Attrition in Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated With Carcinogenesis and Aging

Cytological scoring for pancreatic specimens obtained by endoscopic ultrasound‐guided fine needle aspiration

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