PMID- 32467651
OWN - NLM
STAT- MEDLINE
DCOM- 20211012
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 33
IP  - 12
DP  - 2020 Dec
TI  - ALK rearranged renal cell carcinoma (ALK-RCC): a multi-institutional study of 
      twelve cases with identification of novel partner genes CLIP1, KIF5B and 
      KIAA1217.
PG  - 2564-2579
LID - 10.1038/s41379-020-0578-0 [doi]
AB  - ALK rearranged renal cell carcinoma (ALK-RCC) has recently been included in 2016 
      WHO classification as a provisional entity. In this study, we describe 12 
      ALK-RCCs from 8 institutions, with detailed clinical, pathological, 
      immunohistochemical (IHC), fluorescence in situ hybridization (FISH), and next 
      generation sequencing (NGS) analyses. Patients' age ranged from 25 to 68 years 
      (mean, 46.3 years). Seven patients were females and five were males 
      (M:F = 1:1.4). Tumor size ranged from 17 to 70 mm (mean 31.5, median 25 mm). The 
      pTNM stage included: pT1a (n = 7), pT1b (n = 1), and pT3a (n = 4). Follow-up was 
      available for 9/12 patients (range: 2 to 153 months; mean 37.6 months); 8 
      patients were alive without disease and one was alive with distant metastases. 
      The tumors demonstrated heterogeneous, 'difficult to classify' morphology in 
      10/12 cases, typically showing diverse architectural and cellular morphologies, 
      including papillary, tubular, tubulocystic, solid, sarcomatoid (spindle cell), 
      rhabdoid, signet-ring cell, and intracytoplasmic vacuoles, often set in a 
      mucinous background. Of the remaining two tumors, one showed morphology 
      resembling mucinous tubular and spindle cell renal cell carcinoma (MTSC RCC-like) 
      and one was indistinguishable from metanephric adenoma. One additional case also 
      showed a focal metanephric adenoma-like area, in an otherwise heterogeneous 
      tumor. By IHC, all tumors were diffusely positive for ALK and PAX8. In both cases 
      with metanephric adenoma-like features, WT1 and ALK were coexpressed. ALK 
      rearrangement was identified in 9/11 tumors by FISH. ALK fusion partners were 
      identified by NGS in all 12 cases, including the previously reported: STRN 
      (n = 3), TPM3 (n = 3), EML4 (n = 2), and PLEKHA7 (n = 1), and also three novel 
      fusion partners: CLIP1 (n = 1), KIF5B (n = 1), and KIAA1217 (n = 1). ALK-RCC 
      represents a genetically distinct entity showing a heterogeneous histomorphology, 
      expanded herein to include unreported metanephric adenoma-like and MTSC RCC-like 
      variants. We advocate a routine ALK IHC screening for "unclassifiable RCCs" with 
      heterogeneous features.
FAU - Kuroda, Naoto
AU  - Kuroda N
AD  - Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan.
FAU - Trpkov, Kiril
AU  - Trpkov K
AUID- ORCID: 0000-0003-3142-8846
AD  - Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      AB, Canada.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      AB, Canada.
FAU - Tretiakova, Maria
AU  - Tretiakova M
AD  - Department of Pathology, University of Washington, School of Medicine, Seattle, 
      WA, USA.
FAU - Liu, Yajuan J
AU  - Liu YJ
AD  - Department of Pathology, University of Washington, School of Medicine, Seattle, 
      WA, USA.
FAU - Ulamec, Monika
AU  - Ulamec M
AD  - Ljudevit Jurak Pathology Department, University Clinical Hospital Center Sestre 
      Milosrdice, Zagreb; Pathology Department, Medical Faculty, Zagreb, Croatia.
FAU - Takeuchi, Kengo
AU  - Takeuchi K
AUID- ORCID: 0000-0002-1599-5800
AD  - Division of Pathology and Pathology Project of Molecular Targets, The Cancer 
      Institute, Japanese Foundation for Cancer Research, Tokyo, Japan.
FAU - Agaimy, Abbas
AU  - Agaimy A
AD  - Institute of Pathology, Friedrich-Alexander University Erlangen-Nuremberg, 
      University Hospital of Erlangen, Erlangen, Germany.
FAU - Przybycin, Christopher
AU  - Przybycin C
AD  - Robert J. Tomsich Pathology and Laboratory Medicine Institute and Glickman 
      Urological Institute, Cleveland Clinic, Cleveland, OH, USA.
FAU - Magi-Galluzzi, Cristina
AU  - Magi-Galluzzi C
AD  - Department of Pathology, School of Medicine, University of Alabama, Birmingham, 
      AL, USA.
FAU - Fushimi, Soichiro
AU  - Fushimi S
AD  - Department of Pathology, Himeji Red Cross Hospital, Hyogo, Japan.
FAU - Kojima, Fumiyoshi
AU  - Kojima F
AD  - Department of Human Pathology, Wakayama Medical University, Wakayama, Japan.
FAU - Sibony, Malthide
AU  - Sibony M
AD  - Anatomie et Cytologie Pathologiques, Cochin Hospital, Paris University, Paris, 
      France.
FAU - Hang, Jen-Fan
AU  - Hang JF
AUID- ORCID: 0000-0003-4299-2784
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan.
FAU - Pan, Chin-Chen
AU  - Pan CC
AD  - Department of Pathology and Laboratory Medicine, Taipei Veterans General 
      Hospital, Taipei, Taiwan.
FAU - Yilmaz, Asli
AU  - Yilmaz A
AD  - Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      AB, Canada.
FAU - Siadat, Farshid
AU  - Siadat F
AD  - Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, 
      AB, Canada.
FAU - Sugawara, Emiko
AU  - Sugawara E
AD  - Department of Pathology, Musashino Red Cross Hospital, Tokyo, Japan.
FAU - Just, Pierre-Alexandre
AU  - Just PA
AD  - Anatomie et Cytologie Pathologiques, Cochin Hospital, Paris University, Paris, 
      France.
FAU - Ptakova, Nikola
AU  - Ptakova N
AUID- ORCID: 0000-0002-2561-4717
AD  - Second Faculty of Medicine, Charles University, Prague, Czech Republic.
AD  - Department of Pathology, Faculty of Medicine in Pilsen, Charles University, 
      Pilsen, Czech Republic.
FAU - Hes, Ondrej
AU  - Hes O
AD  - Department of Pathology, Faculty of Medicine in Pilsen, Charles University, 
      Pilsen, Czech Republic. hes@biopticka.cz.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200528
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (KIAA1217 protein, human)
RN  - 0 (KIF5B protein, human)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Neoplasm Proteins)
RN  - 0 (Proteins)
RN  - 148349-95-5 (cytoplasmic linker protein 170)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 3.6.4.4 (Kinesins)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase/*genetics
MH  - Asia
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Renal Cell/enzymology/*genetics/secondary
MH  - Europe
MH  - Female
MH  - *Gene Fusion
MH  - *Gene Rearrangement
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Kidney Neoplasms/enzymology/*genetics/pathology
MH  - Kinesins/*genetics
MH  - Male
MH  - Microtubule-Associated Proteins/*genetics
MH  - Middle Aged
MH  - Neoplasm Proteins/*genetics
MH  - North America
MH  - Proteins/*genetics
MH  - Retrospective Studies
EDAT- 2020/05/30 06:00
MHDA- 2021/10/13 06:00
CRDT- 2020/05/30 06:00
PHST- 2020/02/19 00:00 [received]
PHST- 2020/05/15 00:00 [accepted]
PHST- 2020/05/15 00:00 [revised]
PHST- 2020/05/30 06:00 [pubmed]
PHST- 2021/10/13 06:00 [medline]
PHST- 2020/05/30 06:00 [entrez]
AID - S0893-3952(22)00425-2 [pii]
AID - 10.1038/s41379-020-0578-0 [doi]
PST - ppublish
SO  - Mod Pathol. 2020 Dec;33(12):2564-2579. doi: 10.1038/s41379-020-0578-0. Epub 2020 
      May 28.