PMID- 27565933
OWN - NLM
STAT- MEDLINE
DCOM- 20171207
LR  - 20201218
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 99
DP  - 2016 Sep
TI  - Low homozygous/high heterozygous deletion status by p16 FISH correlates with a 
      better prognostic group than high homozygous deletion status in malignant pleural 
      mesothelioma.
PG  - 155-61
LID - S0169-5002(16)30409-3 [pii]
LID - 10.1016/j.lungcan.2016.07.011 [doi]
AB  - OBJECTIVES: Homozygous deletion (homo-d) of the p16 (CDKN2A) gene, as determined 
      by fluorescence in situ hybridization (FISH), helps differentiate malignant 
      pleural mesothelioma (MPM) from reactive mesothelial hyperplasia (RMH). 
      Heterozygous deletion (hetero-d) has also been identified variably in p16 FISH. 
      This study aimed to investigate the significance of homo-d and hetero-d of p16 in 
      the diagnosis and prognosis of MPM. MATERIALS AND METHODS: p16 FISH was performed 
      in 93 MPMs and 47 RMHs. Real-time polymerase chain reaction (PCR) and methylation 
      specific PCR (MSP) were also performed for cases in which DNA was available. 
      Overall survival (OS) was assessed via the Kaplan-Meier method and logrank test. 
      RESULTS: Cutoff values for homo-d and hetero-d were set at 10% and 47%, 
      respectively, based on p16 FISH results in RMH. In MPM, 80/93 (86.0%) were homo-d 
      positive, and 15/93 (16.1%) were hetero-d positive. No RMH was homo/hetero-d 
      positive. In nine cases of MPM with the low homo-d (<30%)/high hetero-d (>47%) 
      pattern, FISH with a shorter probe caused a slight increase (from 20.1% to 26.5%) 
      in the mean percentage of homo-d and a decrease in that of hetero-d (from 59.6% 
      to 55.6%). Four cases in which the low homo-d/high hetero-d pattern was 
      maintained with the shorter probe were further analyzed by real-time PCR, which 
      separated them into a two (n=2) or one allele deletion group (n=2). MSP revealed 
      no promoter methylation in the two cases with one allele deletion. The OS was 
      significantly shorter in homo-d positive cases (n=24) than homo-d negative cases 
      (n=5, p=0.0002) in the 29 MPM cases with follow-up data. Also, low homo-d/high 
      hetero-d cases (n=5) had a significantly better prognosis than high homo-d (>/=30%) 
      cases (n=17, p=0.011). CONCLUSIONS: Within p16 homo-d positive MPMs with poorer 
      prognosis, the low homo-d/high hetero-d pattern may belong to a better prognostic 
      subgroup in homo-d positive MPMs.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Hamasaki, Makoto
AU  - Hamasaki M
AD  - Departments of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AD  - Departments of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Abe, Sousei
AU  - Abe S
AD  - Departments of Thoracic Surgery, Fukuoka University Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Hamatake, Daisuke
AU  - Hamatake D
AD  - Departments of Thoracic Surgery, Fukuoka University Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Kamei, Toshiaki
AU  - Kamei T
AD  - Pathology and Cytology Center of the PCL Fukuoka, Fukuoka, Japan.
FAU - Hiroshima, Kenzo
AU  - Hiroshima K
AD  - Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 
      Yachiyo, Japan.
FAU - Kawahara, Kunimitsu
AU  - Kawahara K
AD  - Department of Pathology, Osaka Prefectural Hospital Organization, Osaka 
      Prefectural Medical Center for Respiratory and Allergic Disease, Habikino, Japan.
FAU - Sato, Ayuko
AU  - Sato A
AD  - Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
FAU - Tsujimura, Tohru
AU  - Tsujimura T
AD  - Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
FAU - Nakatani, Yukio
AU  - Nakatani Y
AD  - Department of Diagnostic Pathology, Graduate School of Medicine, Chiba 
      University, Chiba, Japan.
FAU - Yoshida, Yasuhiro
AU  - Yoshida Y
AD  - Departments of Thoracic Surgery, Fukuoka University Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Iwasaki, Akinori
AU  - Iwasaki A
AD  - Departments of Thoracic Surgery, Fukuoka University Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Nabeshima, Kazuki
AU  - Nabeshima K
AD  - Departments of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan. Electronic address: kaznabes@fukuoka-u.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20160712
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Female
MH  - *Gene Deletion
MH  - Gene Dosage
MH  - *Genes, p16
MH  - Genetic Association Studies
MH  - Genetic Predisposition to Disease
MH  - *Genotype
MH  - Heterozygote
MH  - Homozygote
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*genetics/*mortality
MH  - Male
MH  - Mesothelioma/*genetics/*mortality
MH  - Mesothelioma, Malignant
MH  - Middle Aged
MH  - Pleural Neoplasms/*genetics/*mortality
MH  - Prognosis
MH  - Survival Analysis
MH  - Young Adult
OTO - NOTNLM
OT  - 9p21 FISH
OT  - Heterozygous deletion
OT  - Homozygous deletion
OT  - Malignant pleural mesothelioma
OT  - Prognosis
OT  - p16
EDAT- 2016/08/28 06:00
MHDA- 2017/12/08 06:00
CRDT- 2016/08/28 06:00
PHST- 2016/03/08 00:00 [received]
PHST- 2016/07/11 00:00 [accepted]
PHST- 2016/08/28 06:00 [entrez]
PHST- 2016/08/28 06:00 [pubmed]
PHST- 2017/12/08 06:00 [medline]
AID - S0169-5002(16)30409-3 [pii]
AID - 10.1016/j.lungcan.2016.07.011 [doi]
PST - ppublish
SO  - Lung Cancer. 2016 Sep;99:155-61. doi: 10.1016/j.lungcan.2016.07.011. Epub 2016 
      Jul 12.