Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors

Tomoda, Ryota; Seto, Masashi; Tsumuki, H.; Iida, Koji; Yamazaki, Takashi; Sonoda, Jun; M.D., and Akihiko Matsumine; Uchida, Atsushi

doi:10.1002/cncr.10793

Cited by 40 publications

(26 citation statements)

References 27 publications

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“…Over-representation of the entire 5p arm was a recurrent event in both cell types with the telomeric end of 5p15.33 showing the greatest amount of change. This region contains the telomerase reverse transcriptase (hTERT) gene which has been implicated in cell immortalisation in numerous cancers (Tomoda et al, 2002;Ramirez et al, 2004). Gain of the 11q13.1 -11q14.1 region was present in 450% of the lung cancer cell lines with the highest degree of concordance at 11q13.3 (Figure 2).…”

Section: Regions Of Similaritymentioning

confidence: 99%

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Coe¹,

Lockwood²,

Girard

et al. 2006

Br J Cancer

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Lung cancer is the leading cause of cancer-related mortality in the world, with small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) comprising the two major cell types. Although these cell types can be distinguished readily at the histological level, knowledge of their underlying molecular differences is very limited. In this study, we compared 14 SCLC cell lines against 27 NSCLC cell lines using an integrated array comparative genomic hybridisation and gene expression profiling approach to identify subtypespecific disruptions. Using stringent criteria, we have identified 159 of the genes that are responsible for the different biology of these cell types. Sorting of these genes by their biological functions revealed the differential disruption of key components involved in cell cycle pathways. Our novel comparative combined genome and transcriptome analysis not only identified differentially altered genes, but also revealed that certain shared pathways are preferentially disrupted at different steps in these cell types. Small cell lung cancer exhibited increased expression of MRP5, activation of Wnt pathway inhibitors, and upregulation of p38 MAPK activating genes, while NSCLC showed downregulation of CDKN2A, and upregulation of MAPK9 and EGFR. This information suggests that cell cycle upregulation in SCLC and NSCLC occurs through drastically different mechanisms, highlighting the need for differential molecular target selection in the treatment of these cancers.

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Section: Regions Of Similaritymentioning

confidence: 99%

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Coe¹,

Lockwood²,

Girard

et al. 2006

Br J Cancer

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“…[23][24][25][26][27][28][29] In some cells, telomerase activity does not uniformly correlate hTERT in giant-cell tumor AE Horvai et al with hTERT mRNA levels, suggesting a role for posttranscriptional modification in controlling enzyme activity. 30 Nevertheless, a growing body of evidence suggests that immunohistochemistry is a reliable surrogate to technically more complex assays.…”

Section: Discussionmentioning

confidence: 99%

“…In some mesenchymal tumors, for example, hTERT expression correlates with aggressive behavior. [23][24][25][26][27][28][29] Taken together, the above studies suggest that immunohistochemistry for hTERT could be used to predict aggressive behavior in giant-cell tumor of bone. Immunohistochemistry also allows direct visualization of the specific cell types with telomerase activity, a characteristic, which may be informative in heterogeneous tumors such as giantcell tumor.…”

mentioning

confidence: 85%

Distribution and prognostic significance of human telomerase reverse transcriptase (hTERT) expression in giant-cell tumor of bone

et al. 2008

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Giant-cell tumor of bone is considered a benign, locally aggressive and rarely metastasizing neoplasm of bone. Specific microscopic or radiographic findings that reliably predict behavior have remained elusive. However, recent evidence suggests that activity of the telomerase enzyme complex correlates with recurrence in giant-cell tumor, although the subset of cells with telomerase activity in these heterogeneous tumors has not been defined. In the present study, we investigated whether immunostaining for human telomerase reverse transcriptase, a component of the telomerase complex, correlates with outcome in giant-cell tumor and the distribution of telomerase reverse transcriptase staining in these tumors. We analyzed 58 cases of giant-cell tumor for the presence and pattern of telomerase reverse transcriptase immunostaining, presence of soft tissue involvement and the type of initial surgery, and correlated these findings with recurrence-free survival and metastasis-free survival. Specific staining with telomerase reverse transcriptase was present in 20 out of 58 tumors (35%) in the nuclei of mononuclear cells and, occasionally, osteoclast-like giant cells. Furthermore, positive telomerase reverse transcriptase immunohistochemistry correlated with recurrence-free survival (P ¼ 0.02), whereas the presence of soft tissue extension (P ¼ 0.3) and the type of initial surgery (P ¼ 0.2) did not. Only soft-tissue extension significantly correlated with metastasis-free survival (P ¼ 0.003). Therefore, telomerase reverse transcriptase expression may predict recurrence in giant-cell tumor insofar as positive immunostaining correlates with shorter recurrence-free survival and may be a useful prognostic marker to stratify patients to more aggressive treatment protocols.

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“…The ALTTMM is more frequent in high-grade compared to low-grade tumors, and it has an increased mitotic index and tumor size compared to non-ALTTMMs [31,39,87]. The picture is less clear with disease progresssion, and metastases are frequently telomerase positive [88,89].…”

Section: Prognosis In Other Tumor Typesmentioning

confidence: 99%

Telomere Maintenance Mechanisms: Prognostic and Therapeutic Implications for the Pathologist and Oncologist

Hung¹,

Hsia²,

Royds³

et al. 2013

OJPathology

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In neoplasia, telomere maintenance mechanisms (TMMs) can be prognostic and may direct therapy in the future. Two types of TMM, telomerase and recombination-based alternative lengthening of telomeres (ALT), result in four prognostic tumor groups when they occur individually, in combination, or in mutual absence. Correct designation of the TMM therefore requires an assessment of telomerase activity and for ALT telomere length distribution and ALT associated promyelocytic leukaemia protein (PML) bodies (APBs). The four groups are associated with differing prognoses that are dependent on the tumor type. As TMM inhibitors are developed, oncologists will require that pathologists determine the TMM, and the treatments will differ accordingly. Furthermore, any anti-TMM therapy administered has the potential to selectively change the TMM used by a tumor, necessitating reassessment of the therapeutic strategy. Herein, we review the telomere maintenance mechanisms, the current diagnostic measures and their utility as prognostic markers in the clinical setting.

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Telomerase activity and human telomerase reverse transcriptase mRNA expression are correlated with clinical aggressiveness in soft tissue tumors

Cited by 40 publications

References 27 publications

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Differential disruption of cell cycle pathways in small cell and non-small cell lung cancer

Distribution and prognostic significance of human telomerase reverse transcriptase (hTERT) expression in giant-cell tumor of bone

Telomere Maintenance Mechanisms: Prognostic and Therapeutic Implications for the Pathologist and Oncologist

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