title: P-cadherin: a useful biomarker for axillary-based breast cancer decisions in the clinical practice.
abstract: Axillary lymph node metastases represent the most powerful breast cancer prognostic factor, dictating disease staging and clinical therapeutic decisions. Nonetheless, breast cancer patients with positive lymph nodes still exhibit a heterogeneous behavior regarding disease progression. Stem-like subpopulations of cancer cells show high migratory and metastatic capacity, thus we hypothesize that breast cancer stem cell markers evaluation in metastasized lymph nodes could provide a more accurate prediction of patient's prognosis. Therefore, the expression profile of P-cadherin, CD44, and CD49f, which have been already associated to stem cell properties in breast cancer, has been evaluated by immunohistochemistry in a series of 135 primary tumors and matched axillary lymph node metastases from 135 breast cancer patients. Taking in consideration the expression of the stem cell markers only in axillary nodes, P-cadherin was the only biomarker significantly associated with poor disease-free and overall patient's survival. Moreover, although a concordant expression between primary tumors and matched lymph nodes has been found in the majority of the cases, a small but significant percentage displayed divergent expression (18.2-26.2%). Remarkably, although CD44 and CD49f changes between primary tumors and lymph node metastasis did not impact survival, the cases that were positive for P-cadherin in lymph node metastases being negative in the primary tumor, presented the worst disease-free and overall survival of the whole series. Accordingly, negative cases for this marker in the lymph nodes with positive expression in the matched breast carcinoma demonstrated a better prognosis, which overlapped with tumors that were negative in both sites. P-cadherin and CD49f gain of expression was mainly found in triple-negative carcinomas. Our results indicate for the first time that the evaluation of P-cadherin expression in lymph node metastases is an important predictor of disease outcome, being a putative valuable marker for axillary-based breast cancer decisions in the clinical practice.
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3s), Universidade do Porto, Porto, Portugal.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.
authors.forename: André Filipe
authors.initials: AF
authors.lastname: Vieira
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3s), Universidade do Porto, Porto, Portugal.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.|Centro Hospitalar de Lisboa Norte (CHLN), Lisboa, Portugal.
authors.forename: Maria Rita
authors.initials: MR
authors.lastname: Dionísio
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3s), Universidade do Porto, Porto, Portugal.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.
authors.forename: Madalena
authors.initials: M
authors.lastname: Gomes
authors.affiliation: Complejo Hospitalario Universitário de Vigo (CHUVI), Vigo, Spain.
authors.forename: Jorge F
authors.initials: JF
authors.lastname: Cameselle-Teijeiro
authors.affiliation: Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.
authors.forename: Manuela
authors.initials: M
authors.lastname: Lacerda
authors.affiliation: Centro Hospitalar de São João (CHSJ), Department of Pathology, Porto, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Amendoeira
authors.affiliation: Laboratoire National de Santé, Department of Pathology and Medicine, Luxembourg.
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.affiliation: Instituto de Investigação e Inovação em Saúde (i3s), Universidade do Porto, Porto, Portugal.|Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal.|Faculdade de Medicina da Universidade do Porto, Porto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Paredes
mesh_terms: D000328:Adult; D000368:Aged; D001365:Axilla; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000032:analysis / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D015820:Cadherins