Combination of assay of human telomerase reverse transcriptase mRNA and cytology using bile obtained by endoscopic transpapillary catheterization into the gallbladder for diagnosis of gallbladder carcinoma.
OBJECTIVE
It is difficult to make accurate diagnoses of polypoid lesions in the gallbladder. To increase the diagnostic accuracy, we have developed an endoscopic technique to obtain gallbladder bile, termed endoscopic transpapillary catheterization into the gallbladder (ETCG). We evaluated the usefulness of a molecular biological approach to the diagnosis of gallbladder carcinoma, in which gallbladder bile obtained by the ETCG technique is used.


METHODS
Twenty patients undergoing an operation because of suspicion of gallbladder carcinoma were enrolled. Twelve patients were confirmed to have gallbladder carcinoma, and four were found to have chronic cholecystitis. Two patients with polypoid lesion were diagnosed as having an inflammatory polyp and a hyperplastic polyp, respectively. The remaining two patients with polypoid lesions were diagnosed as having a cholesterol polyp. Gallbladder bile collected by the ETCG technique was evaluated cytologically and also analyzed for telomerase activity and mRNA for human telomerase reverse transcriptase (hTERT), the catalytic subunit of telomerase. In 14 patients, hTERT mRNA in resected specimens (fixed in 10% formalin and embedded in paraffin) was also examined.


RESULTS
Cytology of gallbladder bile was positive in eight of 11 examined patients (72.7%) with gallbladder carcinoma. hTERT mRNA was detectable in gallbladder bile as well as in resected neoplastic tissues in four of 12 patients (33.3%) with carcinoma. Conversely, telomerase activity was negative in all eight examined patients with carcinoma. Overall, either cytology or hTERT mRNA of gallbladder bile was positive in 10 of 12 patients (83.3%) with gallbladder carcinoma. Cytology, hTERT mRNA, and telomerase activity were negative in eight patients with benign disease.


CONCLUSIONS
The combination of cytology and hTERT mRNA analysis of gallbladder bile might be helpful for the preoperative diagnosis of gallbladder carcinoma.
Uchida
Naohito
N
Third Department of Internal Medicine, Kagawa Medical University, Kagawa, Japan.
Tsutsui
Kunihiko
K
Ezaki
Toru
T
Fukuma
Hiroki
H
Kobara
Hideki
H
Kamata
Hideki
H
Aritomo
Yuichi
Y
Masaki
Tsutomu
T
Watanabe
Seishiro
S
Kobayashi
Shoji
S
Nakatsu
Toshiaki
T
Nakano
Hiroto
H
Kuriyama
Shigeki
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D001646:Bile / Q000737:chemistry; D002277:Carcinoma / Q000175:diagnosis* / Q000601:surgery; D002404:Catheterization; D002763:Cholecystectomy / Q000379:methods; D015331:Cohort Studies; D003581:Cytodiagnosis / Q000379:methods; D004268:DNA-Binding Proteins; D016145:Endoscopy, Digestive System / Q000379:methods; D005260:Female; D005706:Gallbladder Neoplasms / Q000175:diagnosis* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012334:RNA, Neoplasm / Q000032:analysis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D019098:Telomerase