Telomerase activity in pancreatic endocrine tumors

Shou Jiang Tang, John A. Dumot, Liming Wang, Christian Memmesheimer, Darwin L. Conwell, Gregory Zuccaro, Marlene Goormastic, Adrian H. Ormsby, John Kenneth Cowell

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr ± 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type 1 and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.

Original languageEnglish (US)
Pages (from-to)1022-1030
Number of pages9
JournalAmerican Journal of Gastroenterology
Volume97
Issue number4
DOIs
StatePublished - Apr 29 2002

Fingerprint

Telomerase
Acinar Cell Carcinoma
Neoplasms
Insulinoma
Survival
Microscopy
Vipoma
Glucagonoma
Gastrinoma
von Hippel-Lindau Disease
Multiple Endocrine Neoplasia Type 1
Light
Death Certificates
Endocrine Cells
Acinar Cells
Telomere
Secretory Vesicles
Kaplan-Meier Estimate
Hematoxylin
Eosine Yellowish-(YS)

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

Cite this

Tang, S. J., Dumot, J. A., Wang, L., Memmesheimer, C., Conwell, D. L., Zuccaro, G., ... Cowell, J. K. (2002). Telomerase activity in pancreatic endocrine tumors. American Journal of Gastroenterology, 97(4), 1022-1030. https://doi.org/10.1016/S0002-9270(02)03979-5

Telomerase activity in pancreatic endocrine tumors. / Tang, Shou Jiang; Dumot, John A.; Wang, Liming; Memmesheimer, Christian; Conwell, Darwin L.; Zuccaro, Gregory; Goormastic, Marlene; Ormsby, Adrian H.; Cowell, John Kenneth.

In: American Journal of Gastroenterology, Vol. 97, No. 4, 29.04.2002, p. 1022-1030.

Research output: Contribution to journalArticle

Tang, SJ, Dumot, JA, Wang, L, Memmesheimer, C, Conwell, DL, Zuccaro, G, Goormastic, M, Ormsby, AH & Cowell, JK 2002, 'Telomerase activity in pancreatic endocrine tumors', American Journal of Gastroenterology, vol. 97, no. 4, pp. 1022-1030. https://doi.org/10.1016/S0002-9270(02)03979-5
Tang SJ, Dumot JA, Wang L, Memmesheimer C, Conwell DL, Zuccaro G et al. Telomerase activity in pancreatic endocrine tumors. American Journal of Gastroenterology. 2002 Apr 29;97(4):1022-1030. https://doi.org/10.1016/S0002-9270(02)03979-5
Tang, Shou Jiang ; Dumot, John A. ; Wang, Liming ; Memmesheimer, Christian ; Conwell, Darwin L. ; Zuccaro, Gregory ; Goormastic, Marlene ; Ormsby, Adrian H. ; Cowell, John Kenneth. / Telomerase activity in pancreatic endocrine tumors. In: American Journal of Gastroenterology. 2002 ; Vol. 97, No. 4. pp. 1022-1030.
@article{3d3294c31bcf4eeb825356f29129d1fe,
title = "Telomerase activity in pancreatic endocrine tumors",
abstract = "OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95{\%} of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr ± 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type 1 and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92{\%} vs 0{\%} at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93{\%} vs 0{\%} at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.",
author = "Tang, {Shou Jiang} and Dumot, {John A.} and Liming Wang and Christian Memmesheimer and Conwell, {Darwin L.} and Gregory Zuccaro and Marlene Goormastic and Ormsby, {Adrian H.} and Cowell, {John Kenneth}",
year = "2002",
month = "4",
day = "29",
doi = "10.1016/S0002-9270(02)03979-5",
language = "English (US)",
volume = "97",
pages = "1022--1030",
journal = "American Journal of Gastroenterology",
issn = "0002-9270",
publisher = "Nature Publishing Group",
number = "4",

}

TY - JOUR

T1 - Telomerase activity in pancreatic endocrine tumors

AU - Tang, Shou Jiang

AU - Dumot, John A.

AU - Wang, Liming

AU - Memmesheimer, Christian

AU - Conwell, Darwin L.

AU - Zuccaro, Gregory

AU - Goormastic, Marlene

AU - Ormsby, Adrian H.

AU - Cowell, John Kenneth

PY - 2002/4/29

Y1 - 2002/4/29

N2 - OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr ± 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type 1 and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.

AB - OBJECTIVES: Pancreatic endocrine tumors (PETs) have variable prognoses, and predictors of survival are lacking. PETs can be difficult to distinguish histologically from aggressive pancreatic neoplasms such as acinar cell carcinoma. Telomerase is a ribonuclear protein that maintains the length of the telomere and induces cell immortality. Telomerase is present in 95% of pancreatic adenocarcinoma and is associated with aggressive tumor behavior. Our aim is to determine telomerase activity in PETs and investigate its potential role as a prognostic indicator. METHODS: Telomerase detection using the telomeric repeat amplification protocol was performed on frozen surgical archived pancreatic endocrine tissue from 30 patients with PETs identified by light microscopy (hematoxylin-eosin stain). All results were confirmed with internal controls. A patient's survival was measured from the time of surgery. Acinar cell differentiation (presence of zymogen granules) was determined by electron microscopy. Follow-up data were acquired via telephone interview, medical record review, and death certificates. RESULTS: Three of 30 PETs diagnosed by light microscopy were telomerase positive: three were considered nonfunctional, and two of these three patients had extrapancreatic disease. All three telomerase-positive cases were reclassified as either acinar cell carcinoma (two cases) or mixed acinar-endocrine cell carcinoma (one case). All three patients (mean age = 63 yr) died from tumor progression within 2 yr of surgery (mean = 1.6 yr ± 0.5 SD). The remaining PETs were telomerase negative: 13 insulinomas, four nonfunctional, two sporadic glucagonomas, one gastrinoma, one vipoma, one carcinoidlike PET, and five PETs from three patients with multiple endocrine neoplasm syndrome type 1 and two patients with von Hippel-Lindau syndrome. Excluding insulinomas, 12 of 14 patients with telomerase-negative PETs had extrapancreatic disease. Nevertheless, Kaplan-Meier survival estimates for these 12 patients were significantly longer than for patients with telomerase-positive acinar cell carcinoma (92% vs 0% at 2 yr, p = 0.001, log rank test). The survival of all telomerase-negative PETs (n = 27) was significantly longer than that of the patients with telomerase-positive acinar cell carcinoma (93% vs 0% at 2 yr, p = 0.0001). CONCLUSIONS: Telomerase activity helps to identify acinar cell carcinomas that histologically resemble PETs, which accounts for the poor prognosis demonstrated in these patients. The absence of telomerase activity in most PETs may be responsible for their indolent clinical course. Telomerase may identify potentially progressive tumors, such as acinar cell carcinoma, and may be useful in selecting patients for more aggressive treatment.

UR - http://www.scopus.com/inward/record.url?scp=0036120241&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036120241&partnerID=8YFLogxK

U2 - 10.1016/S0002-9270(02)03979-5

DO - 10.1016/S0002-9270(02)03979-5

M3 - Article

C2 - 12003383

AN - SCOPUS:0036120241

VL - 97

SP - 1022

EP - 1030

JO - American Journal of Gastroenterology

JF - American Journal of Gastroenterology

SN - 0002-9270

IS - 4

ER -