PMID- 25634745
OWN - NLM
STAT- MEDLINE
DCOM- 20150820
LR  - 20201218
IS  - 1532-0979 (Electronic)
IS  - 0147-5185 (Linking)
VI  - 39
IP  - 7
DP  - 2015 Jul
TI  - BAP1 immunohistochemistry and p16 FISH to separate benign from malignant 
      mesothelial proliferations.
PG  - 977-82
LID - 10.1097/PAS.0000000000000394 [doi]
AB  - A variety of immunohistochemical (IHC) stains have been proposed to mark either 
      benign or malignant mesothelial proliferations. Loss of the p16 tumor suppressor 
      (CDKN2A), through homozygous deletions of 9p21, is a good marker of mesotheliomas 
      but lacks sensitivity. Recent reports indicate that some mesotheliomas are 
      associated with loss of BRCA-associated protein 1 (BAP1) expression. Here we 
      investigate BAP1 and p16 as potential markers of malignancy and compare test 
      characteristics with previously proposed markers using a well-characterized 
      tissue microarray. BAP1 protein expression was interrogated by IHC. The p16 locus 
      was examined by fluorescence in situ hybridization (FISH) directed toward 
      chromosome 9p21. Loss of BAP1 was identified in 7/26 mesotheliomas and 0/49 
      benign proliferations. Loss of p16 was identified in 14/27 mesotheliomas and 0/40 
      benign proliferations, yielding 100% specificity and positive predictive value 
      for each marker. Together, BAP1 IHC and p16 FISH were 58% sensitive for detecting 
      malignancy. Various combinations of p53, EMA, IMP3, and GLUT1 showed reasonably 
      high specificity (96% to 98%) but poor to extremely poor sensitivity. Combined 
      BAP1 IHC/p16 FISH testing is a highly specific method of diagnosing malignant 
      mesotheliomas when the question is whether a mesothelial proliferation is benign 
      or malignant and is particularly useful when tissue invasion by mesothelial cells 
      cannot be demonstrated. However, combined BAP1/p16 FISH testing is not highly 
      sensitive, and negative results do not rule out a mesothelioma. The 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.
FAU - Sheffield, Brandon S
AU  - Sheffield BS
AD  - *Division of Anatomical Pathology, Vancouver General Hospital double daggerDivision of 
      Anatomical Pathology, Children's and Women's Hospital of British Columbia, 
      Vancouver, BC, Canada daggerPhenoPath Laboratories, Seattle, WA.
FAU - Hwang, Harry C
AU  - Hwang HC
FAU - Lee, Anna F
AU  - Lee AF
FAU - Thompson, Kim
AU  - Thompson K
FAU - Rodriguez, Stephanie
AU  - Rodriguez S
FAU - Tse, Christopher H
AU  - Tse CH
FAU - Gown, Allen M
AU  - Gown AM
FAU - Churg, Andrew
AU  - Churg A
LA  - eng
PT  - Comparative Study
PT  - Evaluation Study
PT  - Journal Article
PL  - United States
TA  - Am J Surg Pathol
JT  - The American journal of surgical pathology
JID - 7707904
RN  - 0 (BAP1 protein, human)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Cell Proliferation
MH  - Cyclin-Dependent Kinase Inhibitor p16/*analysis
MH  - Diagnosis, Differential
MH  - Epithelium/*pathology
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*chemistry/*pathology
MH  - Mesothelioma/*chemistry/*pathology
MH  - Mesothelioma, Malignant
MH  - Sensitivity and Specificity
MH  - Tumor Suppressor Proteins/*analysis
MH  - Ubiquitin Thiolesterase/*analysis
EDAT- 2015/01/31 06:00
MHDA- 2015/08/21 06:00
CRDT- 2015/01/31 06:00
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2015/08/21 06:00 [medline]
AID - 10.1097/PAS.0000000000000394 [doi]
PST - ppublish
SO  - Am J Surg Pathol. 2015 Jul;39(7):977-82. doi: 10.1097/PAS.0000000000000394.