Wnt pathway activation predicts increased risk of tumor recurrence in patients with stage I nonsmall cell lung cancer.

Abstract:

OBJECTIVE:To determine the incidence of Wnt pathway activation in patients with stage I NSCLC and its influence on lung cancer recurrence. BACKGROUND:Despite resection, the 5-year recurrence with localized stage I nonsmall cell lung cancer (NSCLC) is 18.4%-24%. Aberrant Wnt signaling activation plays an important role in a wide variety of tumor types. However, there is not much known about the role the Wnt pathway plays in patients with stage I lung cancer. METHODS:Tumor and normal lung tissues from 55 patients following resection for stage I NSCLC were subjected to glutathione S-transferase (GST) E-cadherin pulldown and immunoblot analysis to assess levels of uncomplexed β-catenin, a reliable measure of Wnt signaling activation. The β-catenin gene was also screened for oncogenic mutations in tumors with activated Wnt signaling. Cancer recurrence rates were correlated in a blinded manner in patients with Wnt pathway-positive and -negative tumors. RESULTS:Tumors in 20 patients (36.4%) scored as Wnt positive, with only 1 exhibiting a β-catenin oncogenic mutation. Patients with Wnt-positive tumors experienced a significantly higher rate of overall cancer recurrence than those with Wnt-negative tumors (30.0% vs. 5.7%, P = 0.02), with 25.0% exhibiting distal tumor recurrence compared with 2.9% in the Wnt-negative group (P = 0.02). CONCLUSIONS:Wnt pathway activation occurred in a substantial fraction of Stage I NSCLCs, which was rarely due to mutations. Moreover, Wnt pathway activation was associated with a significantly higher rate of tumor recurrence. These findings suggest that Wnt pathway activation reflects a more aggressive tumor phenotype and identifies patients who may benefit from more aggressive therapy in addition to resection.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Shapiro M,Akiri G,Chin C,Wisnivesky JP,Beasley MB,Weiser TS,Swanson SJ,Aaronson SA

doi

10.1097/SLA.0b013e31826d81fd

subject

Has Abstract

pub_date

2013-03-01 00:00:00

pages

548-54

issue

3

eissn

0003-4932

issn

1528-1140

journal_volume

257

pub_type

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