Assessment of proliferative activity in colorectal carcinomas by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
The monoclonal antibody Ki-67 and the isospecific monoclonal antibody MIB-1 are routinely used in oncology to assess the proliferation index of tumor cells. A more objective and sensitive method is the determination of the of Ki-67 protein-specific mRNA by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). In 25 resected colorectal adenocarcinomas of different stages and grades we determined between 0.2 and 4.4 amol (10(-18) mol) Ki-67 protein-specific mRNA per microgram total RNA (median = 0.88 amol). The corresponding Ki-67 indices (expressing the percentage of Ki-67/MIB-I positive tumor cells) ranged from 41 to 81% (median = 61%). We found a good correlation between Ki-67 index and mRNA expression (r = 0.75), a significant correlation between both data and tumor stage (primary tumor, regional nodes, metastasis [pTNM] staging classification) (p < 0.001), but not between both data and tumor grade. Both Ki-67 indices (p = 0.05) and mRNA levels (p = 0.014) correlated significantly to the patients' survival. These results demonstrate that the Ki-67 protein-specific quantitative RT-PCR is a useful method for the characterization of tumor cell proliferation.
Duchrow
M
M
Surgical Research Laboratory, Surgical Clinic, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Häsemeyer
S
S
Broll
R
R
Bruch
H P
HP
Windhövel
U
U
D000230:Adenocarcinoma / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D002455:Cell Division; D015179:Colorectal Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis / Q000235:genetics*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013997:Time Factors; D014158:Transcription, Genetic
D019394:Ki-67 Antigen; D012333:RNA, Messenger