Renato Franco1, Francesca Collina2, Maurizio Di Bonito3, Gerardo Botti4, Donatella Montanaro5, Luigi Di Maio6, Bruno Vincenzi7, Gabriella Landi8, Massimiliano D'Aiuto9, Michele Caraglia10, Alfonso Baldi11. 1. Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. r.franco@istitutotumori.na.it. 2. Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. f.collina@istitutotumori.na.it. 3. Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. m.dibonito@istitutotumori.na.it. 4. Pathology Unit, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. gbotti1@alice.it. 5. CEINGE, Biotecnologie Avanzate, Naples, Italy. montanaro@ceinge.unina.it. 6. Department of Surgery, Spirito Santo Hospital, Pescara, Italy. dimaio@medital.net. 7. Department of Medical Oncology, University Campus Bio-Medico, Rome, Italy. b.vincenzi@unicampus.it. 8. Breast Oncology Department, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. g.landi@istitutotumori.na.it. 9. Breast Oncology Department, National Cancer Institute "Fondazione Giovanni Pascale", Naples, Italy. m.daiuto@istitutotumori.na.it. 10. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. michele.caraglia@unina2.it. 11. CEINGE, Biotecnologie Avanzate, and Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. alfonsobaldi@tiscali.it.
Abstract
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.
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 humancancers during their progression. Particularly, low HtrA1 mRNA levels have been observed in breast cancerpatients 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.
Authors: Dorota Zurawa-Janicka; Jarek Kobiela; Tomasz Slebioda; Rafal Peksa; Marcin Stanislawowski; Piotr Mieczyslaw Wierzbicki; Tomasz Wenta; Barbara Lipinska; Zbigniew Kmiec; Wojciech Biernat; Andrzej Jacek Lachinski; Zbigniew Sledzinski Journal: Int J Mol Sci Date: 2020-05-31 Impact factor: 5.923