p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens

doi:10.1016/0046-8177(94)90115-5

Human Pathology

Volume 25, Issue 5, May 1994, Pages 443-448

https://doi.org/10.1016/0046-8177(94)90115-5 Get rights and content

Abstract

To determine the utility of positive p53 protein immunostaining as an adjunct in the diagnosis of malignancy in pleural biopsy specimens, we reviewed 73 recently obtained pleural biopsy specimens that represented the typical range of diagnoses encountered in the evaluation of a proliferative pleural process. Immunohistochemistry was performed on paraffin sections of each biopsy specimen using a monoclonal antibody to the p53 suppressor gene product clone BP53-12 (BioGenex, San Ramon, CA) and a standard capillary gap (Microprobe, Fischer Scientific, Pittsburgh, PA) avidin-biotin complex technique with a citrate buffer antigen retrieval solution. Of the pleural biopsy specimens with unequivocal malignancy, 19 of 40 mesotheliomas and nine of 18 metastatic adenocarcinomas were immunopositive for p53 protein. All 13 of the biopsy specimens with reactive mesothelial hyperplasia or organizing pleuritis were negative. Two pleural biopsy specimens, which were interpreted as suspicious but inconclusive for malignancy, were positive for p53 protein and subsequent pathology specimens confirmed the presence of metastatic carcinoma in both of these biopsy specimens. Our findings suggest that p53 protein immunostaining is relatively sensitive and highly specific in differentiating reactive processes from primary or metastatic malignancies in histopathologically equivocal pleural biopsy specimens.

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Citation Excerpt :
The higher positivity rate in the present study, compared to these studies, may be attributed to the difference in the antibodies used where clone DO-1 MoAb had been used in the current study. VPp958 MoAb was used by Hasteh et al. [20], clone BP53-12 MoAb was used by Cagle et al. [21] and Do-7 MoAb was used by Mayall et al. [16]. Also in Hasteh et al. study [20], all malignant cases had mesothelioma and in Cagle et al. [21], 69% of their studied malignant cases had mesothelioma, while in the present study only two cases had malignant mesothelioma.
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.
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^☆: Presented in part at the 82nd Meeting of the United States and Canadian Academy of Pathology, New Orleans, LA, March 15, 1993.

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Original contributionp53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens☆

Abstract

Lancet

Neoplastic asbestos-induced diseases

Mesothelioma

p53 Mutations in colorectal cancer

Mutation of the p53 gene in human soft tissue sarcomas: Association with abnormalities of the RB1 gene

Oncogene

Aberrant expression of the p53 oncoprotein is a common feature of a wide spectrum of human malignancies

Oncogene

Genetic alterations of the p53 gene are a feature of malignant mesotheliomas

Cancer Res

The p53 tumor suppressor gene

Nature

Mutations in p53 as potential molecular markers for human breast cancer

p53 Expression is common in malignant mesothelioma

Histopathology

Original contribution
p53 immunostaining in the differentiation of reactive processes from malignancy in pleural biopsy specimens☆