Relative contribution of normal and neoplastic cells determines telomerase activity and telomere length in primary cancers of the prostate, colon, and sarcoma Journal Article
| Authors: | Engelhardt, M.; Albanell, J.; Drullinsky, P.; Han, W.; Guillem, J.; Scher, H. I.; Reuter, V.; Moore, M. A. S. |
| Article Title: | Relative contribution of normal and neoplastic cells determines telomerase activity and telomere length in primary cancers of the prostate, colon, and sarcoma |
| Abstract: | Telomerase and telomere length are increasingly investigated as potential diagnostic and prognostic markers in human tumors. Among other factors, telomerase and telomere length may be influenced by the degree of tumor cell content in tumor specimens. We studied telomerase activity and telomere length with concomitant integration of histopathological data to determine whether both were influenced by the amount of tumor cells. We measured telomerase in 153 specimens: in 51 solid tumor blocks; in 51 cryostat sections; and in 51 adjacent normal tissues from patients with sarcoma (n = 10) and colorectal (n = 11) and prostate cancer (n = 30) using the sensitive and rapid detection telomeric repeat amplification protocol assay. Telomere length was determined by telomere restriction fragment Southern blot analysis. From cryostat sections, tumor cell infiltration was assessed. Telomerase activity was detected in all colorectal tumors and sarcomas, as expected. In primary prostate cancer, however, telomerase activity was less frequently observed (14 of 30, 47%). Moreover, a decreased intensity compared to colon cancer and sarcoma was evident (P < 0.001). The median tumor cell infiltration was significantly higher in sarcoma (65%) and colon (30%) compared to prostate cancer (5%; P < 0.001). There was a positive correlation between tumor cell infiltration and telomerase activity (r = 0.89; P < 0.001). Telomere restriction fragments in tumors were shorter compared to the normal tissues with peak differences in colon, sarcoma, and prostate of 1.8, 2.8, and 1 kilobase pairs, respectively (P < 0.002). Our data suggest the presence of a positive correlation between the degree of tumor cell content in human solid tumors and the level of telomerase activity detected. We demonstrated that the amount of tumor cells also affects telomere restriction fragment analysis. Therefore, with the predominance of normal cells in tumor specimens, telomerase activity measured may not reflect the malignant phenotype, and telomere loss may be underestimated. This phenomenon was most evident in prostate cancer. Our results will have implications for the future when telomerase activity and telomere lengths may be used for early screening, diagnosis, and prognosis determinations and when telomerase inhibitors are applied to clinical practice. |
| Keywords: | human tissue; histopathology; adenocarcinoma; telomere; neoplasm proteins; tumor markers, biological; colonic neoplasms; enzyme activity; telomerase; prostate cancer; sarcoma; colorectal neoplasms; cancer invasion; prostatic neoplasms; alkaline phosphatase; neoplastic stem cells; colon cancer; prostate biopsy; cell count; neoplasm invasiveness; frozen sections; soft tissue neoplasms; colon biopsy; southern blotting; restriction fragment length polymorphism; tumor stem cells; humans; prognosis; human; male; priority journal; article |
| Journal Title: | Clinical Cancer Research |
| Volume: | 3 |
| Issue: | 10 |
| ISSN: | 1078-0432 |
| Publisher: | American Association for Cancer Research |
| Date Published: | 1997-10-01 |
| Start Page: | 1849 |
| End Page: | 1857 |
| Language: | English |
| PUBMED: | 9815573 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 17 March 2017 -- Source: Scopus |
Citation Impact
MSK Authors
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91Drullinsky -
414Guillem -
1223Reuter -
1129Scher -
549Moore -
18Han -
19Engelhardt -
12Albanell
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