PMID- 25048628
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20141202
LR  - 20220408
IS  - 1936-5233 (Print)
IS  - 1936-5233 (Electronic)
IS  - 1936-5233 (Linking)
VI  - 7
IP  - 5
DP  - 2014 Oct
TI  - Tumor heterogeneity at protein level as an independent prognostic factor in 
      endometrial cancer.
PG  - 613-9
LID - S1936-5233(14)00073-4 [pii]
LID - 10.1016/j.tranon.2014.06.001 [doi]
AB  - Intratumor heterogeneity implies heterogeneous protein function, facilitating 
      tumor adaptation which results in therapeutic failure. We hypothesized that tumor 
      heterogeneity at protein level may influence the course of the disease. As a 
      single biopsy might not represent the full biologic complexity of the tumor, we 
      have analyzed immunohistochemically four different cores obtained from each 
      primary tumor within the cohort of 364 patients with endometrial cancer (EC). The 
      following proteins were examined: estrogen receptor 1 (ESR1), progesterone 
      receptor, epidermal growth factor receptor, v-erb-b2 erythroblastic leukemia 
      viral oncogene homolog 2, receptor tyrosine-protein kinase erbB-3, v-erb-b2 avian 
      erythroblastic leukemia viral oncogene homolog 4, 
      phosphatidylinositol-4,5-bisphosphate 3-kinase, phosphorylated v-akt murine 
      thymoma viral oncogene homolog 1, v-myc avian myelocytomatosis viral oncogene 
      homolog, DNA topoisomerase II alpha 170 kDa (TOP2A), cyclin-dependent kinase 
      inhibitor 2A (CDKN2A), tumor protein p53, RAD21 homolog, S. pombe, and 
      runt-related transcription factor 1. Particularly strong correlation was found 
      between TOP2A and CDKN2A heterogeneity and higher stage of the disease (P = .0002 
      and P = .0003, respectively). Most correlations with clinicopathologic data were 
      observed for ESR1 heterogeneity that correlated with non-endometrioid carcinomas 
      (P=.02), higher stage (P=.005), grade (P=.01), and the presence of metastases (P 
      = .01). Thirty-nine (11.0%) patients were classified as "globally heterogeneous". 
      Cumulative tumor heterogeneity strongly correlated with the presence of 
      metastases, higher stage, and higher grade of the disease (all P b .05). It also 
      carried negative prognostic value (P=.0008). We show that the degree of 
      heterogeneity in EC might serve as a clinically valid molecular marker.
CI  - Copyright (c) 2014 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Supernat, Anna
AU  - Supernat A
AD  - Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, 
      University of Gdansk and Medical University of Gdansk, 80-211 Gdansk, Poland.
FAU - Lapinska-Szumczyk, Sylwia
AU  - Lapinska-Szumczyk S
AD  - Department of Gynaecology, Gynaecological Oncology and Gynaecological 
      Endocrinology, Medical University of Gdansk, 80-402 Gdansk, Poland.
FAU - Majewska, Hanna
AU  - Majewska H
AD  - Department of Pathomorphology, Medical University of Gdansk, 80-214 Gdansk, 
      Poland.
FAU - Gulczynski, Jacek
AU  - Gulczynski J
AD  - Department of Pathology and Neuropathology, Medical University of Gdansk, 80-211 
      Gdansk, Poland.
FAU - Biernat, Wojciech
AU  - Biernat W
AD  - Department of Pathomorphology, Medical University of Gdansk, 80-214 Gdansk, 
      Poland.
FAU - Wydra, Dariusz
AU  - Wydra D
AD  - Department of Gynaecology, Gynaecological Oncology and Gynaecological 
      Endocrinology, Medical University of Gdansk, 80-402 Gdansk, Poland.
FAU - Zaczek, Anna J
AU  - Zaczek AJ
AD  - Department of Medical Biotechnology, Intercollegiate Faculty of Biotechnology, 
      University of Gdansk and Medical University of Gdansk, 80-211 Gdansk, Poland. 
      Electronic address: azaczek@gumed.edu.pl.
LA  - eng
PT  - Journal Article
DEP - 20140719
PL  - United States
TA  - Transl Oncol
JT  - Translational oncology
JID - 101472619
PMC - PMC4225657
EDAT- 2014/07/23 06:00
MHDA- 2014/07/23 06:01
PMCR- 2014/07/19
CRDT- 2014/07/23 06:00
PHST- 2014/05/14 00:00 [received]
PHST- 2014/06/19 00:00 [revised]
PHST- 2014/06/23 00:00 [accepted]
PHST- 2014/07/23 06:00 [entrez]
PHST- 2014/07/23 06:00 [pubmed]
PHST- 2014/07/23 06:01 [medline]
PHST- 2014/07/19 00:00 [pmc-release]
AID - S1936-5233(14)00073-4 [pii]
AID - 10.1016/j.tranon.2014.06.001 [doi]
PST - ppublish
SO  - Transl Oncol. 2014 Oct;7(5):613-9. doi: 10.1016/j.tranon.2014.06.001. Epub 2014 
      Jul 19.