Faculty Collaboration Database

Increased SIAH expression predicts ductal carcinoma in situ (DCIS) progression to invasive carcinoma. Breast Cancer Res Treat 2011 Oct;129(3):717-24

Date

11/23/2010

Pubmed ID

21088888

Pubmed Central ID

PMC3730842

DOI

10.1007/s10549-010-1254-8

Scopus ID

2-s2.0-80052598428 (requires institutional sign-in at Scopus site)   18 Citations

Abstract

Hyperactivated HER2/Neu/EGFR/RAS signaling is a major growth-promoting pathway known to drive cellular transformation and oncogenesis in breast cancers. HER2 amplification is detected in ~20% of all human breast cancer and is quite prevalent (up to 49%) in ductal carcinoma in situ (DCIS). The E3 ubiquitin ligase SIAH is considered a key downstream "gatekeeper" required for proper HER2/EGFR/RAS signal transduction. Formalin-fixed, paraffin-embedded resection specimens from 65 patients with DCIS treated with wide excision only were stained with an anti-SIAH antibody, and the percentage of tumor and normal adjacent tissue cells positive for SIAH nuclear staining were recorded. Statistical analysis was performed comparing SIAH staining in tumor cells to disease recurrence, histologic type, necrosis, hormone receptor status, and Her2/neu status, as well as nuclear grade. Correlation of SIAH expression in tumor cells with SIAH expression in normal adjacent tissue and age was also examined. Expression levels of SIAH in tumor cells was significantly higher in specimens from patients with recurrence (median = 19%) as compared to patients without recurrence (7%) (P < 0.001). There was also significantly increased SIAH expression in tumors with more aggressive features including comedo morphology (13.5% in comedo vs. 7% in other histologic types, P = 0.014). No significant association was observed between SIAH expression and estrogen receptor, progesterone receptor, and Her2/neu status. There was a significant correlation between SIAH expression in tumors and normal adjacent tissue (Spearman correlation = 0.58, P < 0.001) as well as between SIAH expression in normal adjacent tissue and patient age (Spearman correlation = -0.59, P < 0.001). No significant correlation was identified between patient age and SIAH expression in tumors (Spearman correlation = -0.23, P = 0.067). In conclusion, SIAH may represent a useful prognostic biomarker that predicts DCIS progression to invasive breast cancer.

Author List

Behling KC, Tang A, Freydin B, Chervoneva I, Kadakia S, Schwartz GF, Rui H, Witkiewicz AK

MESH terms used to index this publication - Major topics in bold

Adult
Age Factors
Aged
Aged, 80 and over
Breast Neoplasms
Carcinoma, Intraductal, Noninfiltrating
Disease Progression
Female
Humans
Mastectomy
Middle Aged
Neoplasm Invasiveness
Neoplasm Recurrence, Local
Nuclear Proteins
Predictive Value of Tests
ROC Curve
Reference Values
Ubiquitin-Protein Ligases