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Subtype-Specific Alterations of the Wnt Signaling Pathway in Breast Cancer: Clinical and Prognostic Significance

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Title Subtype-Specific Alterations of the Wnt Signaling
Pathway in Breast Cancer: Clinical and Prognostic
Significance
 
Creator Mukherjee, Nupur
Bhattacharya, Nilanjana
Alam, Neyaz
Roy, Anup
Roychoudhury, Susanta
Panda, Chinmay K
 
Subject Molecular & Human Genetics
 
Description The aim of the study is to understand the importance of the
Wnt ⁄ b-catenin pathway in the development of breast cancer (BC)
and its association with different clinicopathological parameters.
Alterations (deletion ⁄ methylation ⁄ expression) of some Wnt ⁄
b-catenin pathway antagonists like APC, SFRP1 ⁄ 2, CDH1 and activator
b-catenin (CTNNB1) were analyzed in primary BC in Indian
patients. High frequencies (65–70%) of overall alterations (deletion
⁄ methylation) of the antagonists were seen in the BC samples.
Also, 99% (156 ⁄ 158) of the samples showed alterations in any one
of the genes, indicating the importance of this pathway in the
development of this tumor. Co-alterations of these genes were
observed in 30% of samples, with significantly high alterations in
late-onset (37%) and estrogen receptor (ER)) ⁄ progesterone receptor
(PR)) (37%) BC compared with early onset (21%) and ER ⁄ PR+
(18%) BC samples, respectively. Significantly high (P-value =
0.001–0.02) alterations of APC and CDH1 genes were seen in
ER) ⁄ PR) BC compared with ER ⁄ PR+ BC. Immunohistochemical
analysis showed reduced expression of the Wnt antagonists in BC
concordant with their molecular alterations. Nuclear localization
of b-catenin showed significant association with alterations in the
antagonists and was also significantly high in the ER) ⁄ PR) BC
samples. Alterations of SFRP2 coupled with a late clinical stage
and low ⁄ nulliparity predicted the worst prognosis in BC patients.
Therefore, the present study suggests that cumulative alterations
in more than one Wnt antagonist along with increased nuclear
accumulation of b-catenin play an important role in the development
of BC and have significant clinical as well as prognostic
importance.
 
Publisher Oxford University Press
 
Date 2012
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1501/1/CANCER_SCIENCE__103_(2(_210%2D220;2012[58].pdf
Mukherjee, Nupur and Bhattacharya, Nilanjana and Alam, Neyaz and Roy, Anup and Roychoudhury, Susanta and Panda, Chinmay K (2012) Subtype-Specific Alterations of the Wnt Signaling Pathway in Breast Cancer: Clinical and Prognostic Significance. Cancer Science, 103 (2). pp. 210-220.
 
Relation http://dx.doi.org/10.1111/j.1349-7006.2011.02131.x
http://www.eprints.iicb.res.in/1501/