Colorectal carcinomas with high MIB-1 labelling indices but low pKi67 mRNA levels correlate with better prognostic outcome.
OBJECTIVE
Antibodies specific to the proliferation-associated protein pKi67 (e.g. Ki67, MIB-1) are routinely used in oncology to assess the proliferation index of tumour cells. In untransformed cells the amount of pKi67 present at any time of the cell cycle is strictly regulated. To achieve a better understanding of expression and regulation of this protein in tumour cells, we investigated both pKi67 mRNA and protein expression in routinely fixed and embedded tissue of colorectal carcinoma.


RESULTS
We determined a median pKi67 specific in-situ hybridization labelling index of 42% (9-79%) and a median Ki67 index (MIB-1 labelling index) of 59% (26-94%) in 47 resected colorectal adenocarcinomas of different stages and grades. In 32 cases expression of pKi67 mRNA and protein correlated well but we observed a significant difference between both values in 15 tumours. In these cases more than 30% of the cells expressed the protein but not the mRNA of pKi67, possibly due to cell cycle arrest. Patients belonging to this group had a significantly (P < 0.012) better prognosis.


CONCLUSIONS
Tumours with a high pKi67 protein level but low mRNA expression are likely to proliferate more slowly than calculated on the basis of their Ki67 staining index, which possibly explains the patients' improved outcome.
Duchrow
M
M
Surgical Research Laboratory, Surgical Clinic, University Clinic Lübeck, Lübeck, Germany. duchrow@medinf.mu-luebeck.de
Ziemann
T
T
Windhövel
U
U
Bruch
H-P
HP
Broll
R
R
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015870:Gene Expression; D005858:Germany / Q000453:epidemiology; D006785:Hospitals, University; D006801:Humans; D017403:In Situ Hybridization; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000032:analysis; D012189:Retrospective Studies; D015996:Survival Rate
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D019394:Ki-67 Antigen; C440408:MIB-1 antibody; D012333:RNA, Messenger; D012334:RNA, Neoplasm