Decreased expression of p16 in ovarian cancers represents an unfavourable prognostic factor.
Decreased expression of p16 may result from hypermethylation of the promoter or from deletion of the gene. It can lead to intensified proliferation of neoplastic cells and to cytostatic drug resistance. The study was aimed at the examination of prognostic value of p16 expression in relation to Ki67 and caspase-3 in ovarian cancers using immunohistochemistry. The immunohistochemical studies were performed on 73 paraffin-embedded samples of ovarian cancers from 43 patients and samples from 6 healthy ovaries. We have used monoclonal antibodies against p16. ABC method and DAB were used for antigens visualisation. The intensity of the immunohistochemical reactions was appraised using the semi-quantitative IRS scale. In healthy ovaries we have shown strong reaction in the nuclei of surface epithelium. In the case of studied ovarian cancers, the reaction of a nuclear and cytoplasmic localization was obtained. The mean overall immunoreactivity score of nuclear p16 expression amounted to 5.30+/-3.44 SD in primary laparotomy material and 6.61+/-4.34 SD in secondary cytoreduction material. Statistical analysis demonstrated that lower p16 expression was typical of the younger patients and the patients who died. Kaplan-Meier's analysis proved that lower expression of p16 was characteristic of cases with shorter overall survival. In the present study we have demonstrated that lowered p16 expression represented an unfavourable prognostic index in ovarian cancer. Lowered p16 expression was also typical for chemotherapy-resistant ceases (cases of lower caspase-3 and higher Ki67 at secondary cytoreduction expression).
Surowiak
Pawel
P
Charité Campus Mitte, Institute of Pathology, Berlin, Germany.
Materna
Verena
V
Maciejczyk
Adam
A
Pudelko
Marek
M
Suchocki
Slawomir
S
Kedzia
Witold
W
Nowak-Markwitz
Ewa
E
Dumanska
Malgorzata
M
Spaczynski
Marek
M
Zabel
Maciej
M
Dietel
Manfred
M
Lage
Hermann
H
D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary / Q000628:therapy; D014408:Biomarkers, Tumor / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D010053:Ovary / Q000378:metabolism* / Q000473:pathology; D012189:Retrospective Studies; D015996:Survival Rate
D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen; D053453:Caspase 9