Identification of molecular subtypes of triple-negative breast carcinomas based on immunohistochemical profile in women with 45 years or younger and their distribution in the five Brazilian geographic regions

• Grant number: 14/15472-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2015
• End date: February 28, 2017
• Field of knowledge: Health Sciences - Medicine - Maternal and Child Health
• Principal Investigator: Filomena Marino Carvalho
• Grantee: Filomena Marino Carvalho
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Triple-negative breast carcinomas (TNBC) correspond to a heterogeneous group of neoplasia, characterized by lack of expression of estrogen and progesterone receptor, and by the absence of amplification or overexpression of HER2. They are more prevalence among African descendants and younger women. They are often associated with the basal-like genetic phenotype; however, other intrinsic molecular types are included. Genomic analyses of next-generation methods have allowed stratification of TN breast carcinomas into distinct subgroups, explaining the clinical heterogeneity of this group of neoplasias. The identification of these subgroups by immunohistochemical markers is not well explored, although it represents a potential useful tool for the stratification and determination of therapeutic targets. Our aim is to explore the TNBC immunohistochemical profile in patients of 45 year-old or younger, and to investigate possible differences among the five Brazilian geographic regions, considering that these are characterized by different racial distribution, climatic conditions, and life style. We will select samples of tumor from patients 45 years-old or younger, representative of the five Brazilian geographic regions, with invasive carcinoma, available paraffin blocs, and triple-negative immunohistochemical profile. All the cases will be reviewed for the determination of histologic type and grading, and the following pathological features: tumor contour, presence and percentage of in situ component, vascular involvement, type and grade of stromal response, presence of tumoral necrosis, and tubule formation by the neoplasia. Representative tumor areas will be selected for tissue microarray construction and immunohistochemical study. The following markers will be studied: Basal cytokeratins 5/6; luminal cytokeratins 8/18; Epidermal growth factor receptor (EGFR); androgen receptor; e-cadherin; catenin-beta; claudins (3,4 and 7); vimentin; smooth-muscle actin; p63, ALDH1, and Ki-67. According the expression of the markers, the tumor will be grouped as basal-like (basal cytokeratins 5/6 and/or EGFR positive), claudin-low (claudins and/or e-cadherin negative), mesenchymal (vimentin-positive), apocrine (androgen receptor positive), myoepithelial (p63 and/or smooth muscle actin positive), stem-cell (ALDH1-positive), or undefined (negative for all markers, or mixed non-classified). In these subgroups the proliferative activity through the Ki-67 expression will be analyzed. The distribution of the different molecular subtypes among the five geographic regions will be analyzed. The means of age in each of the molecular type and in the different geographic regions will be compared. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

MASILI-OKU, SERGIO MITSUO; LACERDA DE ALMEIDA, BERNARDO GOMES; BACCHI, CARLOS EDUARDO; FILASSI, JOSE ROBERTO; BARACAT, EDMUND CHADA; CARVALHO, FILOMENA MARINO. Lymphocyte-predominant triple-negative breast carcinomas in premenopausal patients: Lower expression of basal immunohistochemical markers. BREAST, v. 31, p. 6-pg., 2017-02-01. (14/15472-8)

MASILI-OKU, SERGIO MITSUO; LACERDA DE ALMEIDA, BERNARDO GOMES; BACCHI, CARLOS EDUARDO; FILASSI, JOSE ROBERTO; BARACAT, EDMUND CHADA; CARVALHO, FILOMENA MARINO. Lymphocyte-predominant triple-negative breast carcinomas in premenopausal patients: Lower expression of basal immunohistochemical markers. BREAST, v. 31, n. SI, p. 34-39, FEB 2017. (14/15472-8)

MASILI-OKU, SERGIO MITSUO; BACCHI, CARLOS EDUARDO; FERNANDES, FELIPE SEABRA; FILASSI, JOSE ROBERTO; BARACAT, EDMUND C.; CARVALHO, FILOMENA MARINO. The Apocrine Profile of Triple-negative Breast Carcinomas in Patients Aged 45 Years or Younger: favorable but rare features. Revista Brasileira de Ginecologia e Obstetrícia, v. 38, n. 10, p. 512-517, OCT 2016. (14/15472-8)