gms | German Medical Science

Objective: Antibodies against the human nuclear antigen pKi-67 (Ki-67, MIB-1) are routinely used in oncology as immune-histological proliferation marker. PKi-67 is exclusively expressed in all active phases of the cell cycle (G1,S, G2, Mitose), not however in resting cells (GO). The Ki-67 index (number of positive stained nuclei compared to all cells) serves as an independent prognostic marker for certain tumor entities. Most antibodies against pKi-67 bind to an immune dominant amino acid sequence (F-K-E-L-F) that is strongly conserved and occures nine times within an alpha-helical structure of the antigen. Our aim was to examine whether colorectal cancer patients express auto-antibodies against pKi-67 and whether this has a prognostic relevance.

Material and methods: A total of 101 sera (36 pre- and 65 post-operative) of colorectal cancer patients operated at our hospital were included in this retrospective study. To detect auto-antibodies, Western blots of nuclear extracts from proliferating HeLa cells were either stained with patients' sera or MIB-1 as positive control. Sera of 20 voluntary healthy donors served as negative control. In addition, the sensitivity of our approach was additionally tested with p53 auto-antibodies on 55 samples.

Results: 13% of the sera proved to be positive for pKi-67 auto-antibodies while the control sera were completely negative. p53 auto-antibodies could be found in 53% of the patient sera. 75% anti-pKi-67 positive samples were also anti-p53 positive. For both antigens we found less positive antibodies in post-operative sera (pKi-67: 9%; p53: 42%) than in pre-operative sera (pKi-67: 19%, p53: 61%). There was, however, no significant correlation between pKi-67 positive sera and tumor stage (I: 13%, II: 4%; III: 23%; IV: 13%), grading or patient's prognosis. Remarkably however is a significant (p=0,023) correlation of pKi-67 positive sera of colon cancer patients (77%) in comparison to rectal cancer patients (60%).

Discussion: PKi-67 auto-antibodies were detectable in 13% of colorectal patients' sera with a statistically significant accumulation in colon carcinoma patients. The percentage of pKi-67 auto-antibodies decreased significantly during the post-operative course. PKi-67 auto-antibodies could be diagnostically valuable in the early detection of neoplasia and could be used as potential markers for recurrent or metastatic disease.