HtrA1 loss is related to aggressive behavior parameters in sentinel node positive breast cancer

Renato Franco¹, Francesca Collina¹, Maurizio Di Bonito¹, Gerardo Botti¹, Donatella Montanaro², Luigi Di Maio³, Bruno Vincenzi⁴, Gabriella Landi⁵, Massimiliano D’Aiuto⁵, Michele Caraglia⁶ and Alfonso Baldi<sup>2,7

1</sup>Pathology Unit, National Cancer Institute “Fondazione Giovanni Pascale”, Naples, ²CEINGE, Biotecnologie Avanzate, Naples, ³Department of Surgery, Spirito Santo Hospital, Pescara, ⁴Department of Medical Oncology, University Campus Bio-Medico, Rome, ⁵Breast Oncology Department, National Cancer Institute “Fondazione Giovanni Pascale”, Naples, ⁶Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples and ⁷Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, Second University of Naples, Naples, Italy

Offprint requests to: Prof. Alfonso Baldi, CEINGE, Biotecnologie Avanzate, Via Gaetano Salvatore, 80145 Naples, Italy. e-mail: alfonsobaldi@tiscali.it or Dr. Renato Franco, Pathology Unit, National Cancer Institute “Giovanni Pascale”, Via Mariano Semmola, 80131 Naples, Italy. e-mail: r.franco@istitutotumori.na.it

Summary. Aim: 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. Subjects and 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. Histol Histopathol 30, 707-714 (2015)

Key words: Breast Cancer, HtrA1, Tumor suppressor, Tissue MicroArray

DOI: 10.14670/HH-30.707