Ph.D. Program in Biomedical Sciences and Oncology

The relevance of the projects we are developing stems from the invaluable opportunity we have to bridge basic and clinical research. The translational research we are dealing with is focused on the identification of markers that may help ameliorate diagnosis, prognosis and response to treatment in order to meet the expectations of the “next generation” of patients.

In breast cancer pathology we have been focusing on the histopathogenesis of breast carcinomas as well as on the characterization of the constellation of genomic alterations of some special histological types of breast cancer and of HER2 positive carcinomas. In particular, the demonstration of the amplification of the centromere of chromosome 17 in HER2 positive carcinomas has had important implications by prompting a revision in the HER2 Scoring system, as highlighted by the latest ASCO/CAP guidelines.

In ER positive carcinomas we have described the role of the androgen receptor as a predictor of favourable outcome. This marker has been recently integrated in a simple and reproducible prognostic index for luminal (ER-positive) breast cancers.

In the field of neuropathology we have described a new diagnostic marker for astroglial-derived tumors, i.e. caveolin-1. Indeed, caveolin-1 is variably expressed in astroglial-derived tumors and    absent in oligodendrogliomas. In addition caveolin-1 expression is also clinically meaningful as it correlates with outcome. Interestingly, such a marker seems to be a promoter of tumour spreading: for example we demonstrated it can be acquired de novo in brain metastases of lung carcinomas.

For the upcoming future, our Unit has planned to focus on several projects with the aim to provide a better understanding of breast cancer progression and response to therapy, as detailed below.

Genetic and proteomic analysis of HER2 positive carcinomas and therapeutic implications (Prof. A. Sapino)

At present, anti-HER2 treatment (trastuzumab) is offered to breast cancer patients provided that HER2 overexpression (IHC) or HER2 gene amplification (FISH) are demonstrated in tumour samples. Clinicians may face treatment dilemmas resulting from cases whose HER2 status (protein and/or gene) is reported as "equivocal" (~20%). Some of the possible phenomena underlying equivocal interpretation in FISH have been described by our group (i.e.: amplification of chromosome 17 centromere) and the step further will be:
1)  to restrain the diagnosis of HER2 equivocal status in breast carcinomas by conventional techniques;
2)  to solve HER2 equivocal status as a result of traditional procedures by introducing alternative techniques suitable for routine diagnosis and reliable for clinical practice.

The relevance of this project is further enhanced by the advent of an antibody-drug conjugate consisting of trastuzumab linked to the cytotoxin mertansine (i.e., T-DM1), which is currently being employed in clinical trials. In such a scenario, it is mandatory to precisely recognize HER2+ carcinomas, because patients will not be administered any other chemotherapeutic agents and response to treatment will rely on the pathological assessment of HER2 only.

Impact of tumour microenvironment on tumour cell dissemination (Prof. A. Sapino)

Breast cancer microenvironment is composed of a complex mixture of cells, secreted proteins and extracellular matrix (ECM). Alterations of the microenvironment are acknowledged as a crucial step in breast cancer progression. Although a precise cellular and molecular characterization of the pro-metastastic tumour microenvironment is still missing, several functional studies support the importance of epithelial-stroma interactions. In our lab we are currently employing distinct techniques that can contribute best understand such a phenomenon:

• cell biology studies with co-cultures of epithelial cancer cells and cancer associated fibroblasts (so called CAFs) from both immortalized and primary cultures;
•  molecular studies such as gene expression profiling following microdissection of single components;
• in situ techniques (immunohistochemistry and in situ hybridization) to best characterize distinct components by visualization on a single glass slide.

Prognostic and predictive markers in breast cancer (Prof. A. Sapino)

In this specific field of interest our lab is supported by a multidisciplinary team composed by radiologists, clinicians, surgeons and radiotherapists with high experience in breast cancer. The general aims are: 

(1) to offer new markers for routine diagnoses that will better address the risk category in breast cancer.
(2) to better understand the intrinsic resistance to chemotherapy treatment and in particular to neoadjuvant treatment in breast cancer.

Molecular and phenotypic predictive markers in anal cancer (Prof. P. Cassoni)

Combined radio-chemotherapy treatment currently represents the standard of care the gold standard in the management of patients affected by anal carcinoma. Even though overall and disease free survival have improved over the years, there are still a significant proportion of patients who do not respond to treatment. A hot topic at the moment is to wok on the identification of morphological, immunophenotypical and molecular prognostic/predictive factors with the aim to best stratify patients according to the most likely response to chemotherapy.

Predictive and prognostic markers in gliomas (Prof. P. Cassoni)

Primitive brain tumours account for about 2% of all tumours in adult patients. Although in the past year molecular portraits of these tumours have been provided (distinct subgroups at the molecular lever), survival is still pretty similar across the subgroups. This is due to a lack of specific targets for tailored therapies and to a lack of knowledge of the true factors predictive of response to both radiotherapy and chemotherapy.
In our lab we aim at identifying prognostic and predictive factors in this scenario by studies on human tissues (immunohistochemistry, PCR, in situ hybridization), tissue cultures (primary and immortalized cell cultures), in vivo studies (creation of xenopatients).