Diagnostic value of p53 and ki67 immunostaining for distinguishing benign from malignant serous effusions

The differentiation of benign mesothelial cells from malignant tumor cells, primary, or metastatic, in serous effusions based on cytomorphologic features alone can be problematic.

This study was conducted to evaluate the utility of p53 and ki67 immunocytochemical markers in differentiating benign from malignant tumor cells in serous effusions.

Archival Papanicolaou-stained smears of 91 pleural and peritoneal effusions were retrieved from Cytology Unit, Pathology Department, NCI, Cairo University between 2008 and 2010. Forty-one cases were positive for malignant cells and 50 cases were benign based on cytomorphologic features. Cases having doubt were excluded from the study. The slides were destained and subjected to immunocytochemical staining for p53 and ki67. Histologic sections of colonic carcinoma and tonsillar tissue were used as positive control for p53 and ki67, respectively. Smears having >5% positively stained nuclei for p53 were taken as positive and labeling index ⩾10% of ki67 was considered positive. Frequencies of the individual immunocytochemical stains; p53 and ki67, in benign and malignant effusion as well as the combination of both stains were calculated.

p53 immunostaining showed nuclear positivity in 31 out of 41 malignant effusions (75.6%) and in 3 out of 50 benign effusions (6%), p<0.005. p53 had 75.6% sensitivity, 94% specificity, 91.2% PPV, and 82.5% NPV. ki67 immunostaining was positive in 30 out of 41 malignant effusions (73.2%) and in 17 out of 50 benign effusions (34%), p<0.05. ki67 had 73.2% sensitivity, 66% specificity, 63.8% PPV, and 75% NPV. Cases were then analyzed for combined immunoprofile of p53 and ki67. Among the 24 cases that coexpressed both antigens, 22 cases (91.7%) were malignant. Thirty two out of 34 cases (94.1%) that showed negative results for both antigens were benign. For the cases that showed p53 immunostaining only, 9 out of 10 cases (90%) were malignant. Fifteen out of 23 cases (65.2%) that showed ki67 immunostaining were benign.

Benign and malignant effusions showed significantly different staining pattern for p53 and ki67. When used individually, p53 immunostaining can truly diagnose 75.6% and 94% of the malignant and benign cases, respectively. ki67 immunostaining can correctly identify 73.2% and 66% of the malignant and benign cases, respectively. When used in combination, 91.7% of p53 and ki67 positive cases were malignant while 94% of p53 and ki67 negative cases were benign. Hence they could be used when the cytomorphology fails to provide a definitive diagnosis.