Alteration of telomeric repeat length in hepatocellular carcinoma is independent of telomerase activity

Nakashio, R.; Kitamoto, Mikiya; Nakanishi, Toshio; Tahara, Hidetoshi; Ide, Toshinori; Asahara, Toshimasa; Kajiyama, Goro

doi:10.3892/ijo.11.1.139

Cited by 6 publications

(8 citation statements)

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“…Another potential source of false‐negatives is of course inadequate sensitivity of the TRAP assay in comparison to other laboratories, which remained a formal possibility despite the use of closely similar protocols. However, assay of serial dilutions of both cell line (293) and tumour tissue (colorectal cancer) confirmed that the detection limit (10–100 ng of protein extract) of our assay for such samples was very similar to that reported by others (5–100 ng)29–32.…”

Section: Discussionsupporting

confidence: 89%

“…In 293 cells, an unequivocal positive result could be obtained with amounts of protein down to 10 ng, but not 1 ng, indicating a detection limit of 1–10 ng; for the colorectal cancer samples the corresponding detection limit was estimated as 10–100 ng (Figure 1). Other studies29–32 using similar material have reported a comparable range of detection limits (5–100 ng), indicating that the TRAP assay, as carried out in our laboratory, is of equivalent sensitivity.…”

Section: Resultssupporting

confidence: 73%

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Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications

et al. 2001

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Despite several recent studies, the biological status and clinical relevance of telomerase expression in tumours derived from the thyroid follicular cell remain controversial. This study has analysed a series of normal, benign, and malignant thyroid samples using two novel approaches: the use of purified epithelial cell fractions to eliminate false-positives due to telomerase-positive infiltrating lymphocytes; and the simultaneous measurement of telomere length to provide a clearer interpretation of telomere dynamics in thyroid neoplasia. The data obtained support the prediction that the epithelial component of non-neoplastic thyroid and of follicular adenomas is telomerase-negative, any positive results being explicable by lymphocyte infiltration. In contrast, many malignant tumours, both follicular and papillary, were telomerase-positive. However, serial dilution of extracts indicated a wide spectrum of activity in these cancers, possibly related to variation in the proportion of telomerase-positive cells. Furthermore, an unexpectedly high proportion were telomerase-negative, a finding which was not explicable by technical problems such as TRAP (telomeric repeat amplification protocol) assay sensitivity. Many of these apparently telomerase-negative tumours had abnormally long telomeres. Correlation of telomerase and telomere length data suggests that thyroid cancers fall into three biological groups: telomerase-positive lesions, consistent with the conventional model of telomere erosion followed by telomerase reactivation; telomerase-negative tumours, which maintain telomere length by a mechanism independent of telomerase; and telomerase-negative tumours which are still undergoing telomere erosion and may therefore be composed of mortal cancer cells. From a clinical standpoint, it is concluded that telomerase detection on unfractionated tissue, such as fine needle aspirates, is of no value as a marker of malignancy in follicular lesions, due to both low sensitivity and specificity.

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Section: Discussionsupporting

confidence: 89%

Section: Resultssupporting

confidence: 73%

Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications

et al. 2001

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“…In high grade DNs, portal tracts are present in smaller numbers and more irregular distribusively from normal liver to chronic hepatitis to cirrho-/ 7bc3$$1246 04-17-98 11:30:27 cana W: Cancer The majority of DNs and LRNs (86%) exhibited telomerase activity levels similar to those of HCCs; plates three or more cells in thickness, unattached ''floating'' cross sections of trabeculae, diffuse pseudohowever, the levels of three lesions were similar to those encountered in a subset of cirrhotic liver samglandular structures, numerous unpaired arteries, moderately irregular nuclear contour, high nuclearples (weak positivity). The use of internal telomerase assay standards 11,26,27 may provide more detailed inforcytoplasmic ratio with significantly increased cell density, reduction of reticulin fibers, and more than rare mation that could be useful in such areas of overlap, although true quantitation cannot yet be performed. mitotic figures.…”

Section: Discussionmentioning

confidence: 99%

“…8 Nevertheless, Separation of low grade DNs from LRNs is even more difficult. According to the International Working weak telomerase activity in cirrhotic liver specimens should be considered to derive from a limited number Party, the most certain way to distinguish between these two types of nodules will be the application of of cells, 27 which is unlikely to be the case in DNs. Further research in this direction is warranted; in situ molecular genetic techniques, which is a prospect for the future.…”

Section: Discussionmentioning

confidence: 99%

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Telomerase activity in precancerous hepatic nodules

Hytiroglou

Kotoula

Thung

et al. 1998

Cancer

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In situdetection of telomerase enzymatic activity in human hepatocellular carcinogenesis

et al. 2001

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Telomerase enzymatic activity has been detected in most human malignant tumours including hepatocellular carcinoma. In order to assess the cellular source, the topographic distribution, and the chronology of telomerase re-expression during human liver carcinogenesis, an in situ technique derived from the standard TRAP (telomeric repeat amplification protocol) assay was set up that allowed the detection of telomerase enzyme activity at the cellular level on frozen liver tissue sections. In situ TRAP (ISTRAP) was performed on 27 hepatocellular carcinomas (HCCs) and 57 non-tumour livers, including normal liver without HCC, liver samples adjacent to tumour with and without hepatic cirrhosis, and biopsies of chronic hepatitis. In HCC, telomerase was detected in the nuclei of liver tumour cells in 23/27 cases (85%), with a heterogeneous distribution within the tumour. This signal was also detected in clusters of hepatocytes in 16/26 (61%) samples of liver adjacent to HCC, in 10/23 (43%) cases of chronic viral hepatitis without adjacent HCC, and in scattered nuclei of 2/8 histologically normal livers. Comparison of the results obtained with ISTRAP and standard TRAP assays on tissue extracts suggests a gain in sensitivity with the in situ technique. This study confirms that telomerase is expressed in most HCCs and suggests that focal telomerase reactivation is an early event during human liver carcinogenesis. ISTRAP is a sensitive technique that allows the study of telomerase expression in the morphological context.

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Alteration of telomeric repeat length in hepatocellular carcinoma is independent of telomerase activity

Cited by 6 publications

References 0 publications

Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications

Telomerase activity and telomere length in thyroid neoplasia: biological and clinical implications

Telomerase activity in precancerous hepatic nodules

In situdetection of telomerase enzymatic activity in human hepatocellular carcinogenesis

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