Molecular Subtypes and Immunohistochemical Profiles in Breast Cancer. Summary of the Doctoral Thesis

Abstract

The doctoral thesis “Molecular subtypes and immunohistochemical profiles in breast cancer” is devoted to morphological and immunohistochemical research on breast cancer. Breast cancer is one of the most common malignant tumours in the European population and the most frequent malignancy in female. In Latvia, the incidence of breast cancer remains significant. Breast cancer is a heterogeneous disease including several entities with different clinical behaviour. The classics of breast cancer characteristics are represented in the classification of breast tumours by the World Health Organization. However, even tumours belonging to the same histologic type can have different clinical course. Additional information can be obtained from molecular subtyping of breast cancer thus disclosing subgroups with different biological properties and response to treatment. The molecular subtypes initially were discovered by gene expression profiling in high throughput microarray technologies. At present, immunohistochemistry is accepted as adequate surrogate marker. In the present work, 5 molecular subtypes of breast cancer (luminal A, luminal B (HER2 positive), luminal B (HER2 negative), HER2 positive and triple negative) are detected according to novel St. Gallen (2011) classification and characterised in detail. Further, new potential prognostic factors are analysed, targeting proteins that are involved in the cardinal tumour features as cell proliferation and cell cycle control (cyclin D1), evasion of apoptosis (BCL2 oncoprotein), expression of oncoproteins due to mutations in proto-oncogenes (p53) and angiogenesis (cyclooxygenase-2). The theoretical basis of the doctoral thesis employs 247 literature sources. The aim of the doctoral thesis was to classify breast cancer by molecular subtypes and to evaluate the above listed novel prognostic factors by immunohistochemistry. Within the research work, 383 patients with primary invasive breast cancer were enrolled. The tumour tissues were evaluated by morphological, immunohistochemical visualisation and in situ hybridisation technologies. In the result, 4 immunohistochemical technologies for the detection of p53, BCL2 protein, cyclooxygenase-2 and cyclin D1 have been developed, 5 molecular subtypes of breast cancer are characterised in detail and the molecular portraits of p53, BCL2, cyclooxygenase-2 and cyclin D1-positive breast cancers are obtained. The complex evaluation of the prognostic value of several factors, revealed that the local spread (pT) of breast cancer, regional lymph nodes status (pN) cancer grade and molecular subtype as well as expression of p53 and BCL2 influences the survival.