Quantification of telomerase activity in sporadic colorectal carcinoma: association with tumor growth and venous invasion.
BACKGROUND
Activation of telomerase, a ribonucleoprotein enzyme complex that synthesizes telomere repeats, is associated with acquisition of unlimited cellular proliferation and is commonly detected in human cancer. Measurement of telomerase activity (TA) may provide important information as a diagnostic marker or a prognostic indicator. The authors studied the quantification of TA and assessed its utility as a prognostic marker in sporadic colorectal carcinoma.


METHODS
Sixty surgical specimens, including 30 specimens of cancer tissue and 30 specimens of corresponding normal colorectal mucosa, were examined. TA was measured by a fluorescence-based telomeric repeat amplification protocol assay. The authors determined the telomerase index (TI = log (A-B), where A represented TA of cancer tissues and B represented TA of normal mucosa) and examined the relation between TI and clinicopathologic factors using the Student t test, analysis of variance, the Chi-square test, and the Fisher PLSD as a post hoc test.


RESULTS
TA of cancer and corresponding normal mucosa was 51.87+/-27.38 and 7.14+/-9.85, respectively (P<0.0001). The cutoff value was determined to be 26 in a receiver operating characteristic study, with 90% sensitivity, 96.7% specificity, and 96.4% positive predictive value. TI was closely correlated with depth of invasion (P = 0.0129) but not with age, gender, histologic type, location, lymph node metastasis, lymphatic infiltration, or Dukes stage. There was a significant difference in TI between tumors with and without venous invasion (P = 0.0003). Four of five tumors with synchronous liver metastasis showed high TI (1.555 <TI).


CONCLUSIONS
High TI may be a risk factor for metastasis of colorectal carcinoma to the liver.
Shoji
Y
Y
Second Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan.
Yoshinaga
K
K
Inoue
A
A
Iwasaki
A
A
Sugihara
K
K
D000230:Adenocarcinoma / Q000201:enzymology* / Q000473:pathology / Q000556:secondary; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis; D001808:Blood Vessels / Q000473:pathology; D002455:Cell Division; D016009:Chi-Square Distribution; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology; D008207:Lymphatic Metastasis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D012004:Rectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D012680:Sensitivity and Specificity; D012737:Sex Factors; D019098:Telomerase / Q000032:analysis*
D014408:Biomarkers, Tumor; D019098:Telomerase