PMID- 15793301
OWN - NLM
STAT- MEDLINE
DCOM- 20050517
LR  - 20221207
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 166
IP  - 4
DP  - 2005 Apr
TI  - Genomic amplification of the human telomerase gene (TERC) in pap smears predicts 
      the development of cervical cancer.
PG  - 1229-38
AB  - Invasive cervical carcinomas almost invariably carry extra copies of chromosome 
      arm 3q, resulting in a gain of the human telomerase gene (TERC). This provided 
      the rationale for the development of a multicolor fluorescence in situ 
      hybridization (FISH) probe set as a diagnostic tool for the direct detection of 
      TERC gains in Pap smears. We previously used this probe set to show that cervical 
      intraepithelial neoplasia (CIN) 2 and CIN3 lesions could be distinguished from 
      normal samples, atypical squamous cell of undetermined significance (ASCUS) and 
      CIN1, with a sensitivity and specificity exceeding 90%, independent of the 
      cytomorphological assessment. In the current study, we explored whether gain of 
      3q and amplification of TERC could predict progression from CIN1/CIN2 to CIN3 and 
      invasive carcinoma. We applied our probe set to a series of 59 previously stained 
      Pap smears for which repeat Pap smears and clinical follow-up were available. The 
      samples included CIN1/CIN2 lesions that progressed to CIN3 (progressors), 
      CIN1/CIN2 lesions that regressed spontaneously (regressors), and normal Pap 
      smears from women who subsequently developed CIN3 or cervical cancer. Here, we 
      show that progressors displayed a gain of 3q whereas none of the regressors 
      showed this genetic aberration. These data suggest that 3q gain is required for 
      the transition from CIN1/CIN2 to CIN3 and that it predicts progression. Of note, 
      3q gain was found in 33% of cytologically normal Pap smears from women who were 
      diagnosed with CIN3 or invasive cervical carcinoma after a short latency. The 
      sensitivity of our test for predicting progression from CIN1/CIN2 to CIN3 was 
      100% and the specificity, ie, the prediction of regression, was 70%. We conclude 
      that the detection of 3q gain and amplification of TERC in routinely collected 
      Pap smears can assist in identifying low-grade lesions with a high progression 
      risk and in decreasing false-negative cytological screenings.
FAU - Heselmeyer-Haddad, Kerstin
AU  - Heselmeyer-Haddad K
AD  - Genetics Branch, Center for Cancer Research/NCI/NIH, 50 South Dr., Bethesda, MD 
      20892, USA.
FAU - Sommerfeld, Kathrin
AU  - Sommerfeld K
FAU - White, Nicole M
AU  - White NM
FAU - Chaudhri, Nadia
AU  - Chaudhri N
FAU - Morrison, Larry E
AU  - Morrison LE
FAU - Palanisamy, Nallasivam
AU  - Palanisamy N
FAU - Wang, Zhen Yuan
AU  - Wang ZY
FAU - Auer, Gert
AU  - Auer G
FAU - Steinberg, Winfried
AU  - Steinberg W
FAU - Ried, Thomas
AU  - Ried T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (telomerase RNA)
RN  - 63231-63-0 (RNA)
RN  - EC 2.7.7.49 (Telomerase)
SB  - IM
MH  - Adult
MH  - Biomarkers, Tumor/*analysis
MH  - Disease Progression
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Middle Aged
MH  - Papanicolaou Test
MH  - RNA/*genetics
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Telomerase/*genetics
MH  - Uterine Cervical Neoplasms/*genetics/*pathology
MH  - Vaginal Smears
MH  - Uterine Cervical Dysplasia/*genetics/*pathology
PMC - PMC1602397
EDAT- 2005/03/29 09:00
MHDA- 2005/05/18 09:00
PMCR- 2005/10/01
CRDT- 2005/03/29 09:00
PHST- 2005/03/29 09:00 [pubmed]
PHST- 2005/05/18 09:00 [medline]
PHST- 2005/03/29 09:00 [entrez]
PHST- 2005/10/01 00:00 [pmc-release]
AID - S0002-9440(10)62341-3 [pii]
AID - 10.1016/S0002-9440(10)62341-3 [doi]
PST - ppublish
SO  - Am J Pathol. 2005 Apr;166(4):1229-38. doi: 10.1016/S0002-9440(10)62341-3.