PMID- 25031015
OWN - NLM
STAT- MEDLINE
DCOM- 20141222
LR  - 20240102
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 465
IP  - 5
DP  - 2014 Nov
TI  - Clinicopathological characteristics of anaplastic carcinoma of the pancreas with 
      rhabdoid features.
PG  - 531-8
LID - 10.1007/s00428-014-1631-5 [doi]
AB  - Undifferentiated (anaplastic) carcinoma with rhabdoid features is a rare and 
      aggressive subtype of pancreatic carcinoma. Here, we report the clinical, 
      histological, and immunohistochemical phenotypes in six autopsy cases of 
      anaplastic carcinoma with rhabdoid features. The patients ranged between 44 and 
      76 years of age (median, 61 years) and consisted of four males and two females. 
      All patients except one case died within 3 months of diagnosis, as these tumors 
      were found at an advanced stage and were chemoresistant. At autopsy, tumor masses 
      measuring 4-22 cm in maximum diameter were mainly located in the pancreatic body 
      and tail. Microscopically, all cases showed anaplastic carcinoma with rhabdoid 
      features that were discohesive with round to polygonal eosinophilic cytoplasm 
      with occasional inclusions, and that had vesicular nuclei, and prominent 
      nucleoli. Immunohistochemistry showed that the rhabdoid cells, particularly the 
      inclusions, were strongly positive for pan-cytokeratin (AE1/AE3) and vimentin. 
      Meanwhile, downregulation or aberrant cytoplasmic localization with focal 
      aggregation of E-cadherin, beta-catenin, and EMA were frequently observed in the 
      rhabdoid cells. Moreover, the intracytoplasmic inclusions were labeled with 
      selective autophagy-related molecules including p62/SQSTM1, ubiquitin, and 
      kelch-like ECH-associated protein 1 (KEAP1). In addition, nuclear factor 
      erythroid 2-related factor 2 (NRF2) and overexpression of its target molecule 
      multidrug resistance-associated protein 1 (MRP1) were commonly observed in the 
      rhabdoid cells. Therefore, these results suggest that p62-mediated aggregation of 
      ubiquitinated intermediate filaments and membranous proteins is an important 
      phenomenon in the rhabdoid phenotype. Indeed, the ubiquitinated aggregates of p62 
      and KEAP1 would induce activation of NRF2 and upregulation of MRP1, leading to 
      potential chemoresistance of anaplastic carcinoma with rhabdoid features.
FAU - Sano, Makoto
AU  - Sano M
AD  - Division of Pathology, Department of Pathology and Microbiology, Nihon University 
      School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan, 
      sano.makoto@nihon-u.ac.jp.
FAU - Homma, Taku
AU  - Homma T
FAU - Hayashi, Emiko
AU  - Hayashi E
FAU - Noda, Hiroko
AU  - Noda H
FAU - Amano, Yusuke
AU  - Amano Y
FAU - Tsujimura, Ryusuke
AU  - Tsujimura R
FAU - Yamada, Tsutomu
AU  - Yamada T
FAU - Quattrochi, Brian
AU  - Quattrochi B
FAU - Nemoto, Norimichi
AU  - Nemoto N
LA  - eng
PT  - Journal Article
DEP - 20140717
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (Vimentin)
RN  - 68238-35-7 (Keratins)
RN  - Y49M64GZ4Q (multidrug resistance-associated protein 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Autopsy
MH  - Biomarkers, Tumor/biosynthesis
MH  - Carcinoma/*pathology
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - Keratins/biosynthesis
MH  - Male
MH  - Middle Aged
MH  - Multidrug Resistance-Associated Proteins/biosynthesis
MH  - Pancreatic Neoplasms/*pathology
MH  - Vimentin/biosynthesis
EDAT- 2014/07/18 06:00
MHDA- 2014/12/23 06:00
CRDT- 2014/07/18 06:00
PHST- 2014/03/05 00:00 [received]
PHST- 2014/07/07 00:00 [accepted]
PHST- 2014/06/18 00:00 [revised]
PHST- 2014/07/18 06:00 [entrez]
PHST- 2014/07/18 06:00 [pubmed]
PHST- 2014/12/23 06:00 [medline]
AID - 10.1007/s00428-014-1631-5 [doi]
PST - ppublish
SO  - Virchows Arch. 2014 Nov;465(5):531-8. doi: 10.1007/s00428-014-1631-5. Epub 2014 
      Jul 17.