title: Increased SIAH expression predicts ductal carcinoma in situ (DCIS) progression to invasive carcinoma.
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.
authors.affiliation: Department of Pathology, Thomas Jefferson University and Kimmel Cancer Center, Philadelphia, PA 19107, USA. kathryn.behling@jeffersonhospital.org
authors.forename: Kathryn C
authors.initials: KC
authors.lastname: Behling
authors.forename: Amy
authors.initials: A
authors.lastname: Tang
authors.forename: Boris
authors.initials: B
authors.lastname: Freydin
authors.forename: Inna
authors.initials: I
authors.lastname: Chervoneva
authors.forename: Sameep
authors.initials: S
authors.lastname: Kadakia
authors.forename: Gordon F
authors.initials: GF
authors.lastname: Schwartz
authors.forename: Hallgeir
authors.initials: H
authors.lastname: Rui
authors.forename: Agnieszka K
authors.initials: AK
authors.lastname: Witkiewicz
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006801:Humans; D008408:Mastectomy / Q000379:methods; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D009687:Nuclear Proteins / Q000378:metabolism*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012016:Reference Values; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
chemical_list: D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins