PMID- 21531815
OWN - NLM
STAT- MEDLINE
DCOM- 20111017
LR  - 20110617
IS  - 1557-3265 (Electronic)
IS  - 1078-0432 (Linking)
VI  - 17
IP  - 12
DP  - 2011 Jun 15
TI  - Prospective gene signature study using microRNA to identify the tissue of origin 
      in patients with carcinoma of unknown primary.
PG  - 4063-70
LID - 10.1158/1078-0432.CCR-10-2599 [doi]
AB  - PURPOSE: Accurate identification of tissue of origin (ToO) for patients with 
      carcinoma of unknown primary (CUP) may help customize therapy to the putative 
      primary and thereby improve the clinical outcome. We prospectively studied the 
      performance of a microRNA-based assay to identify the ToO in CUP patients. 
      EXPERIMENTAL DESIGN: Formalin-fixed paraffin-embedded (FFPE) metastatic tissue 
      from 104 patients was reviewed and 87 of these contained sufficient tumor for 
      testing. The assay quantitates 48 microRNAs and assigns one of 25 tumor diagnoses 
      by using a biologically motivated binary decision tree and a K-nearest neighbors 
      (KNN). The assay predictions were compared with clinicopathologic features and, 
      where suitable, to therapeutic response. RESULTS: Seventy-four of the 87 cases 
      were processed successfully. The assay result was consistent or compatible with 
      the clinicopathologic features in 84% of cases processed successfully (71% of all 
      samples attempted). In 65 patients, pathology and immunohistochemistry (IHC) 
      suggested a diagnosis or (more often) a differential diagnosis. Out of those, the 
      assay was consistent or compatible with the clinicopathologic presentation in 55 
      (85%) cases. Of the 9 patients with noncontributory IHC, the assay provided a ToO 
      prediction that was compatible with the clinical presentation in 7 cases. 
      CONCLUSIONS: In this prospective study, the microRNA diagnosis was compatible 
      with the clinicopathologic picture in the majority of cases. Comparative 
      effectiveness research trials evaluating the added benefit of molecular profiling 
      in appropriate CUP subsets are warranted. MicroRNA profiling may be particularly 
      helpful in patients in whom the IHC profile of the metastasis is nondiagnostic or 
      leaves a large differential diagnosis.
CI  - (c)2011 AACR.
FAU - Varadhachary, Gauri R
AU  - Varadhachary GR
AD  - Departments of Gastrointestinal Medical Oncology and Pathology, The University of 
      Texas MD Anderson Cancer Center, Houston, Texas, USA.
FAU - Spector, Yael
AU  - Spector Y
FAU - Abbruzzese, James L
AU  - Abbruzzese JL
FAU - Rosenwald, Shai
AU  - Rosenwald S
FAU - Wang, Huamin
AU  - Wang H
FAU - Aharonov, Ranit
AU  - Aharonov R
FAU - Carlson, Heather R
AU  - Carlson HR
FAU - Cohen, Dalia
AU  - Cohen D
FAU - Karanth, Siddharth
AU  - Karanth S
FAU - Macinskas, Joanna
AU  - Macinskas J
FAU - Lenzi, Renato
AU  - Lenzi R
FAU - Chajut, Ayelet
AU  - Chajut A
FAU - Edmonston, Tina B
AU  - Edmonston TB
FAU - Raber, Martin N
AU  - Raber MN
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110429
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents/therapeutic use
MH  - Carcinoma/*diagnosis/genetics/*secondary
MH  - Decision Trees
MH  - Female
MH  - *Gene Expression Profiling
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Neoplasms, Unknown Primary/*diagnosis/drug therapy/genetics
MH  - Prospective Studies
MH  - Treatment Outcome
MH  - Young Adult
EDAT- 2011/05/03 06:00
MHDA- 2011/10/18 06:00
CRDT- 2011/05/03 06:00
PHST- 2011/05/03 06:00 [entrez]
PHST- 2011/05/03 06:00 [pubmed]
PHST- 2011/10/18 06:00 [medline]
AID - 1078-0432.CCR-10-2599 [pii]
AID - 10.1158/1078-0432.CCR-10-2599 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2011 Jun 15;17(12):4063-70. doi: 10.1158/1078-0432.CCR-10-2599. 
      Epub 2011 Apr 29.