G-C 8 Tumour Histopathology and Neuropathology
The Tumor Histopathology and Neuropathology Group, based at the Department of Pathology of Germans Trias Hospital, is led by Prof Aurelio Ariza, MD, PhD. It is a multidisciplinary team composed of pathologists, biologists, and biochemists who work on human tissues, cells, and their products, collaborating with many other research groups on the campus. Their common strategy is to approach the molecular mechanisms of cancer (cutaneous, lymphoid, gastrointestinal, brain) and neurodegeneration (synucleionopathies) from a morphological perspective rooted in pathology.
The work of the group integrates morphomolecular and clinical approaches applicable to clinical and basic research within the same laboratories on a daily basis. This integration means that all the members of the group are engaged in truly translational research in an efficient and sustainable manner. The attainment of this goal is reflected in the list of publications and patent applications.
The work of the group is organized by three Principal Investigators:
- Aurelio Ariza MD, PhD, Principal Investigator and Group Leader
- Katrin Beyer PhD, Principal Investigator on Miguel Servet Contract
- Mª Teresa Fernández-Figueras MD, Chief of Section
Line 1: Skin tumours
Actinic keratosis (AK), a form of intraepidermal squamous cell carcinoma, is the forerunner of most cases of invasive squamous cell carcinoma (CIS). It has been proposed that progression to invasive tumor requires dedifferentiation within the entire thickness of the epithelium. Some authors have divided progressive dedifferentiation into three stages of keratinocyte intraepithelial neoplasia (KIN), similar to the path followed by undifferentiated vulvar neoplasms. However, there are cases in which infiltration occurs directly from the basal layer of the epidermis, similar to the differentiation pathway in the vulva, larynx and oral cavity. There have been only a few studies to assess the importance of the two pathways (differentiated and undifferentiated) and their mechanisms.
The epidermis surrounding squamous carcinoma is representative of the precursor lesion and may provide reliable information about the process of tumor progression.
In this context we are evaluating the involvement of different HPV types in CIS genesis and the presence of markers that correlate with CEI transformation and tumor aggressiveness using tissue arrays.
Line 2: Lymphomas
One of our recent projects aims to determine miRNA expression profiles in the presence or absence of MYC, Bcl2 and BCL6 gene translocations, as well as the immunophenotype, in a series of aggressive lymphomas in HIV-positive and HIV-negative patients with homogeneous treatment. In order to detect possible prognostic markers, the results are correlated with HIV status so as to identify specific lymphoma profiles associated with HIV infection, clinical parameters and survival.
Additionally, we are studying the IRF4 gene translocation in anaplastic lymphomas to assess its diagnostic and eventual prognostic value in these tumors.
Line 3: Gastrointestinal tumors
During the last few years we have developed, consolidated and validated a diagnostic algorithm for Lynch syndrome in colorectal adenocarcinoma. This diagnostic algorithm has been further enhanced by the inclusion of immunohistochemical EpCAM determination. Additionally, lesions developing in the context of serrated polyposis syndrome have been characterized at both the morphological and molecular levels. We have also furthered the study of polypoid precursor lesions of colorectal carcinoma in both sporadic and hereditary contexts. As a result, we have established additional morphological and molecular criteria that allow a more accurate diagnosis of these tumors.
Line 4: Central nervous system tumors
Recently, various genetic subtypes of glioblastoma (GB) have been described that have prognostic implications and could possibly respond to new therapeutic modalities, such as anti-angiogenic therapies. In this line, and along with other Catalan hospitals, we have been awarded a grant from the TV3 Marathon Foundation to study gene expression profiles (GEPs) in a group of 200 GB cases and to correlate the results with clinical, radiological, pathological, and immunophenotypic variables. Consequently, we will carry out immunohistochemical determinations with an antibody panel representing all those proteins for which GEP studies suggest a possible role as markers for the identification of different molecular GB subtypes.
Additionally, we are studying infiltating gliomas to better define the molecular alterations taking place in signaling pathways including ALK, c-MET or Ros1.
Line 5: Genomics and transcriptomics of synucleinopathies
In this research line we focus on the molecular characterization of Lewy body diseases. In this context we have established expression profiles of different transcript variants from genes primarily involved in disease development in post-mortem brain samples.
An important highlight in our research has been the characterization of the first molecular subgroup of dementia with Lewy bodies (DLB), published in 2010 in Brain. This finding has opened new avenues in the research of Lewy body diseases and revealed the possible existence of a new therapeutic target for at least one specific subgroup of DLB patients.
A very special research interest of ours is the detection of new diagnostic markers in peripheral blood. So far we have identified three potential biomarkers; two of them are specific for DLB subgroups, whereas the third may serve as an early diagnostic marker of DLB. These findings have given rise to four patents. One of these patents, filed in 2015, has been extended worldwide (WO2011/104023).
The Tumour Histopathology and Neuropathology Groups has collaborations with many different groups. Here is a selection of our publications:
- Publications by Ariza, A and Musulen, E (to 2015)
- Publications by Ariza, A and Tapia G
- Publications Fernández-Figueras MT
- Publications by Beyer, K and Ariza A
- Publications by Carrato, C and Balañà C
Aurelio Ariza, Group Leader
(+34) 93 497 88 53