PI3K pathway activation in high-grade ductal carcinoma in situ-implications for progression to invasive breast carcinoma Journal Article


Authors: Sakr, R. A.; Weigelt, B.; Chandarlapaty, S.; Andrade, V. P.; Guerini Rocco, E.; Giri, D.; Ng, C. K. Y.; Cowell, C. F.; Rosen, N.; Reis-Filho, J. S.; King, T. A.
Article Title: PI3K pathway activation in high-grade ductal carcinoma in situ-implications for progression to invasive breast carcinoma
Abstract: Purpose: To assess the prevalence of phosphoinositide 3-kinase (PI3K) pathway alterations in pure highgrade ductal carcinoma in situ (DCIS) and DCIS associated with invasive breast cancer (IBC), and to determine whether DCIS and adjacent IBCs harbor distinct PI3K pathway aberrations. Experimental Design: Eighty-nine cases of pure high-grade DCIS and 119 cases of high-grade DCIS associated with IBC were characterized according to estrogen receptor (ER) and HER2 status, subjected to immunohistochemical analysis of PTEN, INPP4B, phosphorylated (p)AKT and pS6 expression, and to microdissection followed by Sequenom genotyping of PIK3CA and AKT1 hotspot mutations. Results: Alterations affecting the PI3K pathway were found in a subset of pure DCIS and DCIS adjacent to IBC. A subtype-matched comparison of pure DCIS and DCIS adjacent to IBC revealed that PIK3CA hotspot mutations and pAKT expression were significantly more prevalent in ER-positive/HER2-negative DCIS adjacent to IBC (P values, 0.005 and 0.043, respectively), and that in ER-negative/HER2-positive cases INPP4B loss of expression was more frequently observed in pure DCIS (a P value of 0.013). No differences in the parameters analyzed were observed in a pairwise comparison of the in situ and invasive components of cases of DCIS and adjacent IBC. Analysis of the PIK3CA-mutant allelic frequencies in DCIS and synchronous IBC revealed cases in which PIK3CA mutations were either restricted to the DCIS or to the invasive components. Conclusion: Molecular aberrations affecting the PI3K pathway may play a role in the progression from high-grade DCIS to IBC in a subset of cases (e.g., a subgroup of ER-positive/HER2-negative lesions). © 2014 AACR.
Journal Title: Clinical Cancer Research
Volume: 20
Issue: 9
ISSN: 1078-0432
Publisher: American Association for Cancer Research  
Date Published: 2014-05-01
Start Page: 2326
End Page: 2337
Language: English
DOI: 10.1158/1078-0432.ccr-13-2267
PROVIDER: scopus
PMCID: PMC4015460
PUBMED: 24634376
DOI/URL:
Notes: Clin. Cancer Res. -- Export Date: 2 June 2014 -- CODEN: CCREF -- Source: Scopus
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MSK Authors
  1. Neal Rosen
    406 Rosen
  2. Dilip D Giri
    165 Giri
  3. Tari King
    177 King
  4. Rita Sakr
    61 Sakr
  5. Victor Piana De Andrade
    27 Andrade
  6. Britta Weigelt
    456 Weigelt
  7. Kiu Yan Charlotte Ng
    155 Ng
  8. Catherine Frances Cowell
    10 Cowell