A Caderina-P é um potencial biomarcador para a tomada de decisões clínicas em carcinoma de mama com metastização axilar

Uma equipa de investigadores do i3S/Ipatimup descobriu que a análise do marcador estaminal caderina-P em gânglios metastizados de cancro de mama permite uma melhor estratificação da sobrevida e do tempo livre de doença dos pacientes. Especificamente, a pesquisa do biomarcador caderina-P foi mais eficiente nesta estratificação do que os marcadores clássicos CD44 e CD49f, sendo que o ganho daquele marcador nos gânglios linfáticos metastizados (Vs. tumor primário) está associado a características mais agressivas da doença. Este estudo foi realizado pelo grupo EPIC- Interações Epiteliais em Cancro, sobre a orientação da investigadora Joana Paredes e teve a colaboração do Centro Hospitalar de Lisboa Norte, do Centro Hospitalar Universitário de Vigo e do Hospital de S. João.

Autores e Afiliações:

André Filipe Vieira*^1,2, Maria Rita Dionísio*^1,2,3 Madalena Gomes^1,2,
Jorge F Cameselle-Teijeiro⁴, Manuela Lacerda², Isabel Amendoeira⁵, Fernando Schmitt⁶ and Joana Paredes^1,2,7

¹Instituto de Investigação e Inovação em Saúde (i3s), Universidade do Porto, Porto, Portugal;

²Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Porto, Portugal;

³Centro Hospitalar de Lisboa Norte (CHLN), Lisboa, Portugal;

⁴Complejo Hospitalario Universitário de Vigo (CHUVI), Vigo, Spain;

⁵Centro Hospitalar de São João (CHSJ), Department of Pathology, Porto, Portugal;

⁶Laboratoire National de Santé, Department of Pathology and Medicine, Luxembourg;

⁷Faculdade de Medicina da Universidade do Porto, Porto, Portugal.

*These authors equally contributed to this work.

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.

Revista: Modern Pathology

Link: http://www.nature.com/modpathol/journal/vaop/ncurrent/full/modpathol2016232a.html