title: New biomarkers to predict the evolution of in situ breast cancers.
abstract: BACKGROUND
  Genomic studies have shown that gene expression profiles are similar in in situ (CIS) and invasive breast cancers, suggesting that several biofunctional modifications of the transformation process occur before or during the development of CIS lesion.
  
  
  METHODS
  We investigated 3 biomarkers in 44 patients with CIS: TG2 (transglutaminase 2), HJURP (Holliday junction recognition protein), and HIF-1α (hypoxia inducible factor-1 alpha).
  
  
  RESULTS
  TG2 was more highly expressed than the other two markers and significantly more so in stromal than in tumor cells. HIF-1α evaluation showed a higher expression in both tumor and stromal cells in patients with relapsed G3 tumors, indicating a potential role of this marker in CIS evolution. A greater than sevenfold higher risk of relapse (P = 0.050) was observed in patients highly expressing HJURP in stroma and a tenfold higher recurrence risk (P = 0.026) was seen in those with a higher stromal HIF-1α expression. An important increase in risk accuracy (AUC 0.80) was obtained when HIF-1α and HJURP were evaluated together.
  
  
  CONCLUSIONS
  Despite the limited number of relapsed patients, we formulated some hypotheses on the factors responsible for malignant evolution and recurrence which are now being tested in a large case series with a longer follow-up.
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Bravaccini
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: M M
authors.initials: MM
authors.lastname: Tumedei
authors.affiliation: Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Scarpi
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: W
authors.initials: W
authors.lastname: Zoli
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Rengucci
authors.affiliation: Pathology Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Serra
authors.affiliation: Breast Surgery Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Curcio
authors.affiliation: Breast Surgery Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Buggi
authors.affiliation: Breast Surgery Unit, Morgagni-Pierantoni Hospital, 47121 Forlì, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Folli
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Rocca
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Maltoni
authors.affiliation: Pathology Unit, Santa Maria delle Croci Hospital, 48010 Ravenna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Puccetti
authors.affiliation: Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Amadori
authors.affiliation: Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST), IRCCS, 47014 Meldola, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Silvestrini
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002278:Carcinoma in Situ / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008875:Middle Aged; D012008:Recurrence; D017154:Stromal Cells / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C524371:HJURP protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit