title: HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer.
abstract: OBJECTIVE
  HtrA1, a member of the High Temperature Requirement Factor A family of oxidative stress-response proteases seems to play a role as a tumor suppressor, being down-regulated in a series of human cancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancer patients with more aggressive clinical features. These have been shown to relate to a longer disease free and overall survival, with more pronounced effects in axillary nodes positive patients.
  
  
  METHODS
  We have analyzed for immunohistochemical HtrA1 expression a series of 66 sentinel node positive breast cancers through Tissue Micro Array technology.
  
  
  RESULTS
  HtrA1 was absent to low in 29 cases, medium in 19 cases and high in 18 cases. Our data revealed a positive significant relation between HtrA1 expression level and estrogen (p=0,002) and progestinic receptor expression (p=0.003) and a negative correlation with histological grading (p=0.028), proliferation index (p=0.05), common BC histotypes (p=0.040), luminal A and B subtypes (p=0.001), metastasis development (p<0.0001) and local relapse (p<0.0001). Finally, no correlation was recorded between HtrA1 expression level and breast cancer histology type and metastasis to non sentinel nodes. Interestingly HtrA1 loss in SLN metastasis was able to predict positive non sentinel nodes (p=0.001).
  
  
  CONCLUSIONS
  Low HtrA1 expression is significantly related to breast cancer poor prognosis parameters, and HtrA1 loss in sentinel nodes is related to metastasis of non sentinel nodes, offering a further marker useful for BC prognostic stratification.
authors.affiliation: Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. r.franco@istitutotumori.na.it.
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.affiliation: Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. f.collina@istitutotumori.na.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Collina
authors.affiliation: Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. m.dibonito@istitutotumori.na.it.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Bonito
authors.affiliation: Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. gbotti1@alice.it.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: CEINGE, Biotecnologie Avanzate, Naples, Italy. montanaro@ceinge.unina.it.
authors.forename: Donatella
authors.initials: D
authors.lastname: Montanaro
authors.affiliation: Department of Surgery, Spirito Santo Hospital, Pescara, Italy. dimaio@medital.net.
authors.forename: Luigi
authors.initials: L
authors.lastname: Di Maio
authors.affiliation: Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy. b.vincenzi@unicampus.it.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vincenzi
authors.affiliation: Breast Oncology Department, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. g.landi@istitutotumori.na.it.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Landi
authors.affiliation: Breast Oncology Department, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. m.daiuto@istitutotumori.na.it.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: D'Aiuto
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. michele.caraglia@unina2.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: CEINGE, Biotecnologie Avanzate, and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. alfonsobaldi@tiscali.it.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D005260:Female; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D021701:Sentinel Lymph Node Biopsy; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases