PMID- 31454632
OWN - NLM
STAT- MEDLINE
DCOM- 20200610
LR  - 20200610
IS  - 1532-8392 (Electronic)
IS  - 0046-8177 (Linking)
VI  - 93
DP  - 2019 Nov
TI  - Correlation between immunohistochemistry and RICTOR fluorescence in situ 
      hybridization amplification in small cell lung carcinoma.
PG  - 74-80
LID - S0046-8177(19)30157-1 [pii]
LID - 10.1016/j.humpath.2019.08.018 [doi]
AB  - Small cell lung carcinoma (SCLC) accounts for approximately 15% of all lung 
      cancers and remains a challenging disease, with no significant improvement in the 
      field of targeted therapies. The RICTOR gene (rapamycin-insensitive companion of 
      mTOR [mammalian target of rapamycin]), which encodes a key structural (scaffold) 
      protein of mTOR complex 2), has recently been identified as one of the most 
      frequently amplified genes and a potential therapeutic target in SCLC. The aim of 
      this study was to compare immunohistochemical (IHC) expression of Rictor and 
      phospho-Akt (a downstream target of mTOR complex 2) with RICTOR amplification as 
      detected by fluorescence in situ hybridization (FISH) in SCLC. RICTOR FISH and 
      Rictor and phospho-Akt IHC staining were performed on 100 formalin-fixed, 
      paraffin-embedded SCLC samples. RICTOR amplification was detected in 15 samples 
      (15%). IHC positivity for Rictor and phospho-Akt was observed in 37 (37%) and 42 
      (42%) samples, respectively. Considering FISH as the diagnostic standard, the 
      sensitivity and specificity of Rictor IHC were 93% and 73%, whereas the 
      sensitivity and specificity of phospho-Akt IHC were 80% and 65%, respectively. 
      Rictor expression was higher in distant metastases than in primary tumor samples 
      and lymph node metastases. There was no association between RICTOR amplification 
      and clinical outcome. However, high expression of either Rictor or phospho-Akt 
      was associated with significantly decreased overall survival. In conclusion, IHC 
      expression of Rictor correlates highly with RICTOR amplification. Therefore, 
      Rictor IHC can be used as a cost-effective method to select patients for RICTOR 
      FISH and, potentially, for mTORC1/2 inhibitor therapy.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Krencz, Ildiko
AU  - Krencz I
AD  - 1st Department of Pathology and Experimental Cancer Research, Semmelweis 
      University, Budapest, Hungary H-1085.
FAU - Sebestyen, Anna
AU  - Sebestyen A
AD  - 1st Department of Pathology and Experimental Cancer Research, Semmelweis 
      University, Budapest, Hungary H-1085.
FAU - Papay, Judit
AU  - Papay J
AD  - 1st Department of Pathology and Experimental Cancer Research, Semmelweis 
      University, Budapest, Hungary H-1085.
FAU - Lou, Yanyan
AU  - Lou Y
AD  - Division of Hematology and Medical Oncology, Mayo Clinic, Jacksonville, FL 32224.
FAU - Lutz, Gabrielle F
AU  - Lutz GF
AD  - Clinical Research Internship Study Program, Mayo Clinic, Jacksonville, FL 32224.
FAU - Majewicz, Tracy L
AU  - Majewicz TL
AD  - Department of Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, FL 
      32224.
FAU - Khoor, Andras
AU  - Khoor A
AD  - Department of Laboratory Medicine & Pathology, Mayo Clinic, Jacksonville, FL 
      32224. Electronic address: Khoor.Andras@mayo.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190824
PL  - United States
TA  - Hum Pathol
JT  - Human pathology
JID - 9421547
RN  - 0 (RICTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Female
MH  - Gene Amplification/genetics
MH  - Humans
MH  - *Immunohistochemistry/methods
MH  - *In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/diagnosis/*metabolism/pathology
MH  - Lymphatic Metastasis/diagnosis
MH  - Male
MH  - Mechanistic Target of Rapamycin Complex 1/metabolism
MH  - Middle Aged
MH  - Rapamycin-Insensitive Companion of mTOR Protein/*metabolism
MH  - Small Cell Lung Carcinoma/diagnosis/*metabolism/pathology
OTO - NOTNLM
OT  - Fluorescence in situ hybridization
OT  - Immunohistochemistry
OT  - Phospho-Akt
OT  - RICTOR
OT  - Small cell lung carcinoma
EDAT- 2019/08/28 06:00
MHDA- 2020/06/11 06:00
CRDT- 2019/08/28 06:00
PHST- 2019/06/03 00:00 [received]
PHST- 2019/08/16 00:00 [revised]
PHST- 2019/08/18 00:00 [accepted]
PHST- 2019/08/28 06:00 [pubmed]
PHST- 2020/06/11 06:00 [medline]
PHST- 2019/08/28 06:00 [entrez]
AID - S0046-8177(19)30157-1 [pii]
AID - 10.1016/j.humpath.2019.08.018 [doi]
PST - ppublish
SO  - Hum Pathol. 2019 Nov;93:74-80. doi: 10.1016/j.humpath.2019.08.018. Epub 2019 Aug 
      24.