p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma

  title={p16 FISH Deletion in Surface Epithelial Mesothelial Proliferations Is Predictive of Underlying Invasive Mesothelioma},
  author={Harry C. Hwang and Christopher H Tse and Stephanie A Rodriguez and Allen M. Gown and Andrew Churg},
  journal={The American Journal of Surgical Pathology},
  • H. HwangC. Tse A. Churg
  • Published 1 May 2014
  • Medicine, Biology
  • The American Journal of Surgical Pathology
An atypical mesothelial proliferation along the pleural or peritoneal surface without evidence of invasive tumor poses a diagnostic challenge. Homozygous deletion of p16 (CDKN2A) by fluorescence in situ hybridization (FISH) has been shown to be a good marker of malignancy in mesothelial proliferations, but correlations of p16 status between atypical surface proliferations and underlying mesothelioma have not been described. We used p16 FISH to investigate 11 pleural and 7 peritoneal… 

Deletion status of p16 in effusion smear preparation correlates with that of underlying malignant pleural mesothelioma tissue

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Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma

Loss of BAP1 expression in atypical mesothelial proliferation helps to predict malignant mesothelioma and is a useful adjunct test in these cases, while homozygous deletion of CDKN2A in mesotheric cell proliferations did not prove to be useful to predict MM.

BAP1 Immunohistochemistry and p16 FISH to Separate Benign From Malignant Mesothelial Proliferations

Together, BAP1 IHC and p16 FISH testing is not highly sensitive, and negative results do not rule out a mesothelioma, but the test characteristics of previously proposed markers EMA, p53, GLUT1, IMP3 suggest that these markers are not useful tools in this clinical setting.

New Markers for Separating Benign From Malignant Mesothelial Proliferations: Are We There Yet?

In the context of a mesothelial proliferation, the finding of homozygous deletion of p16 by FISH or loss of BAP1 by immunohistochemistry is, thus far, 100% specific for malignant mesothelioma.

Malignant mesothelioma in situ diagnosed by methylthioadenosine phosphorylase loss and homozygous deletion of CDKN2A: a case report

The case of a MIS is reported in a 73-year-old male with a history of asbestos exposure presenting with massive pleural effusion in the right thoracic cavity, leading to the diagnosis of MIS.

BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations

BAP1 immunostain represents an excellent biomarker with an unprecedented specificity in the distinction between benign and malignant mesothelioma and other mesothelial proliferations and is commonly associated with homozygous BAP1 deletion.

Utility of BAP1 Immunohistochemistry and p16 (CDKN2A) FISH in the Diagnosis of Malignant Mesothelioma in Effusion Cytology Specimens

Both BAP1 immunohistochemistry and p16 FISH analysis provide reliable markers of mesothelial malignancy in effusion cytology specimens, especially where the atypical mesothelioma proliferation is well sampled.

Use of p16 FISH for differential diagnosis of mesothelioma in smear preparations

It was shown that the p16 deletion status of MPM cells in pleural effusions reflected that of the underlying invasive MPM tissues, indicating the usefulness of p16 FISH in effusion smear cytology for MPM diagnosis, and proposed to perform p 16 FISH as often as possible for differentiating MPM from RMC.

The pathologists and team at PhenoPath

Combined BAP1/p16 FISH testing is not highly sensitive, and negative results do not rule out a mesothelioma, but test characteristics of previously proposed markers EMA, p53, GLUT1, IMP3 suggest that, even in combination, these markers are not useful tools in this clinical setting.



Diagnostic importance of 9p21 homozygous deletion in malignant mesotheliomas

This study suggests that 9p21 homozygous deletion assessed by FISH on paraffin-embedded tissue may be helpful for differentiating between malignant mesotheliomas and reactive mesothelial proliferations.

Diagnostic usefulness of p16/CDKN2A FISH in distinguishing between sarcomatoid mesothelioma and fibrous pleuritis.

The distinction between sarcomatoid mesothelioma and fibrous pleuritis is difficult based on histology, especially when the amount of tumor tissue examined via biopsy is small and immunohistochemical

Challenges and controversies in the diagnosis of mesothelioma: Part 1. Cytology-only diagnosis, biopsies, immunohistochemistry, discrimination between mesothelioma and reactive mesothelial hyperplasia, and biomarkers

No tissue or serum marker has been proved to have sufficient specificity, consistency and reproducibility that it can replace evidence of invasion as the decisive marker for diagnosis when there is any uncertainty concerning a diagnosis of epithelioid mesothelioma.

FISH assay development for the detection of p16/CDKN2A deletion in malignant pleural mesothelioma

Distinction between benign and malignant mesothelial proliferations can be diagnostically challenging and FISH for p16/CDKN2A deletion is a useful test for confirming the diagnosis of MPM.

The Separation of Benign and Malignant Mesothelial Proliferations

The separation of benign from malignant mesothelial proliferations has emerged as a major problem in the pathology of the serosal membranes and keratin staining is of no help in separating benign and malignant proliferations because both are keratin-positive.

The use of CDKN2A deletion as a diagnostic marker for malignant mesothelioma in body cavity effusions

The distinction between benign reactive mesothelial cells and malignant mesothelial cells in serous effusions is difficult and has an unusually high false negative rate. Unfortunately, there are no

The diagnostic utility of p16 FISH and GLUT-1 immunohistochemical analysis in mesothelial proliferations.

Two promising ancillary tests used in the diagnosis of mesothelioma include GLUT-1 immunohistochemical analysis and fluorescence in situ hybridization (FISH) testing for the p16 deletion. This study

IMP3 and GLUT-1 Immunohistochemistry for Distinguishing Benign From Malignant Mesothelial Proliferations

Both IMP3 and GLUT-1 are more frequently positive in malignant compared with benign mesothelial processes; however, the frequency of positive staining in benign cases is too high to allow their diagnostic use as single stains.

p16 Deletion in sarcomatoid tumors of the lung and pleura.

Despite statistically significant differences in the frequency of 9p21 deletion, this genetic abnormality cannot be used as a reliable diagnostic tool in the assessment of sarcomatoid lesions of the lung and pleura.

Guidelines for pathologic diagnosis of malignant mesothelioma: 2012 update of the consensus statement from the International Mesothelioma Interest Group.

These guidelines are meant to be a practical reference for the pathologist and recommend that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question.