Differential expression of telomerase reverse transcriptase (hTERT) in lung tumours.
Human telomerase reverse transcriptase is a ribonucleoprotein that synthesises telomeric sequences, which decrease at each cell division. In cancer cells, its activity is linked to telomere maintenance leading to unlimited cellular proliferation and immortality. To evaluate the prognostic value of the catalytic subunit telomerase reverse transcriptase (hTERT), we analysed its expression by immunohistochemistry in 122 formalin-fixed lung tumours including 42 squamous cell carcinoma (SCC), 43 adenocarcinoma (ADC), 19 basaloid carcinoma (BC) and 18 small-cell lung carcinoma (SCLC) in comparison with detection of hTERT mRNA by in situ hybridisation and relative telomerase activity by TRAP assay in a subset of tumours. We observed a high concordance between hTERT protein expression and detection of hTERT mRNA and telomerase activity. Telomerase expression varied according to histology (P=0.0002) being significantly lower in ADC than in SCC, BC and SCLC (P<0.0001). Adenocarcinoma and SCC exhibited either a nuclear or a nucleolar staining in contrast with a diffuse nuclear staining observed in most BC and all SCLC (P=0.01). In stage I NSCLC telomerase expression was lower than in other stages (P=0.04), and a nucleolar staining was correlated with a short survival (P=0.03). We concluded that telomerase expression and pattern are distinctive among histopathological classes of lung cancer and convey prognostic influence.
Lantuejoul
S
S
Service de Pathologie Cellulaire, Institut A Bonniot, CHU Michallon Grenoble, France.
Soria
J C
JC
Moro-Sibilot
D
D
Morat
L
L
Veyrenc
S
S
Lorimier
P
P
Brichon
P Y
PY
Sabatier
L
L
Brambilla
C
C
Brambilla
E
E
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology*; D020134:Catalytic Domain; D004268:DNA-Binding Proteins; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis; D019098:Telomerase / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D019098:Telomerase