Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity.
OBJECTIVE
Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are aggressive neoplasms associated with a variable response to systemic therapies. Therefore, the identification of biomarkers to better characterise this heterogeneity would improve treatment efficacy. The aim of this study was to evaluate the influence of androgen receptor (AR) and oestrogen receptor (ER) on clinicopathological features in a series of HER2-positive breast carcinomas.


METHODS
A total of 104 carcinomas were selected and reviewed. Immunohistochemical studies for ER, progesterone receptor and Ki-67 were analysed on tumour whole histological sections. AR expression was analysed on samples represented on tissue microarrays. According to steroid receptor expression, cases were classified into three groups: AR positive/ER positive (48 cases), AR positive/ER negative (41 cases) and AR negative/ER negative (13 cases).


RESULTS
AR-positive tumours corresponded to 89 (85.6%) of 104 carcinomas. AR-positive carcinomas were associated with a higher frequency of ER and progesterone receptor co-expression and lower proliferative activity determined by the expression of Ki-67. AR-negative carcinomas were more often high grade. The group of AR-positive/ER-negative carcinomas was associated with the highest frequency of apocrine morphological features. The group of AR-negative/ER-negative carcinomas was associated with the highest proliferative activity and the highest frequency of high histological and nuclear grade. The lowest frequency of high-grade tumours and the lowest proliferative activity were seen among tumours with expression of both receptors.


CONCLUSIONS
These results suggest that co-expression of AR and ER can provide a protective effect based on phenotypical presentation of HER2-positive carcinomas. Furthermore, lack of both steroid hormone receptors characterises the most aggressive phenotype.
Department of Obstetrics and Gynecology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Francini de Mattos Lima
Fde M
Lin
Katia Maciel
KM
Pincerato
Carlos Eduardo
CE
Bacchi
Edmund Chada
EC
Baracat
Filomena Marino
FM
Carvalho
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D014408:Biomarkers, Tumor / Q000032:analysis*; D001938:Brazil; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D049109:Cell Proliferation; D016009:Chi-Square Distribution; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000032:analysis; D008875:Middle Aged; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D011944:Receptors, Androgen / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis; D018570:Risk Assessment; D012307:Risk Factors; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C410798:AR protein, human; C508053:ERBB2 protein, human