Projects / Programmes
Characteristics of Malignant Neoplasms Important for Diagnosis, Prognosis and Treatment Outcome
January 1, 2009
- December 31, 2013
| Code |
Science |
Field |
Subfield |
| 3.04.00 |
Medical sciences |
Oncology |
|
| Code |
Science |
Field |
| B200 |
Biomedical sciences |
Cytology, oncology, cancerology |
| B520 |
Biomedical sciences |
General pathology, pathological anatomy |
| B490 |
Biomedical sciences |
Haematology, extracellular fluids |
| Code |
Science |
Field |
| 3.05 |
Medical and Health Sciences |
Other medical sciences |
cancer, prognostic factors, immunohistochemistry, tissue microarrays, cytometry, fine needle aspiration biopsy
Researchers (23)
Organisations (2)
Abstract
Microscopic examination of routinely stained slides with tumor tissue and the study of its morphology still plays the primary role in diagnosis of malignant and premalignant processes; however, their phenotypic and genetic characteristics can nowadays be better assessed by a number of modern techniques, such as immunocytochemistry, molecular biology and genetics, and flow and image cytometry. The aim of our study is to evaluate the value of these methods in diagnosis, prognostication and treatment planning in selected fields of oncology.
In the field of breast tumors, our research will be focused on early breast carcinoma. Prognostic value of various immunohistochemical markers will be assessed on a large number of tumors from patients with long follow-up using the tissue microarray (TMA) technology. Further studies will involve patients with axillary lymph node micrometastases. The incidence of these has been increasing due to extensive use of sentinel lymph node biopsy approach; however, their biologic significance is not clear.
The main area of research in the field of soft tissue tumors will be a retrospective study of tumors showing muscle differentiation, i.e. leiomyosarcoma and rhabdomyosarcoma, as well as tumors of the PNET/ES (primitive neuroectodermal tumor / Ewing sarcoma) group.
Another area of research will encompass malignant lymphomas and leukemias. Here, the focus will be on assessment of their phenotype and genotype and their changes during treatment, disease regression and progression. The feasibility of immunology, cytogenetics and molecular biology in the assessment of disease persistence or complete eradication will also be evaluated. Another area of concern will be immunophenotyping of fine needle aspiration biopsy (FNAB) samples obtained from lymph nodes and evaluation of its utility in diagnosis and follow up. FNAB material will also be used to prospectively study changes in thyroid carcinomas undergoing treatment with chemotherapy.
A part of the program will be devoted to studying preneoplastic changes, in particular those in the breast and uterine cervix; and to studying malignancy associated changes (MAC), i.e. changes that occur in non-neoplastic cells in the individuals with cancer. These changes can be detected by image cytometry and may have potential in early cancer detection.
Significance for science
Prior to the beginning of treatment, 114 patients with B-cell lymphoma treated with rituximab and chemotherapy had CD20 expression assessed by quantitative flow cytometric measurements. Patients who achieved complete response after rituximab therapy had a significantly higher expression of the CD20 antigen and longer overall survival than patients with a CD20 expression level below the cut-off value. In 43 MSI-H colorectal cancers we searched for new targets of promoter methylation, inspected the nature of methylation process, and the influence of methylation at specific CpG site on gene expression. CpG methylation was detected in 12 tumor suppressor genes. According to the detected methylation pattern, two groups of tumors, significantly differing in age, exist in MSI-H colorectal cancers. Our study also suggests that methylation at a specific CpG island in the promoter could be the representative for gene silencing and therefore serve as a biomarker. The clinical course of chronic lymphocytic leukemia (CLL) can be indolent or very aggressive. ZAP-70 protein expression has been shown as a potentially useful prognostic marker to predict the course of the disease. The majority of studies on ZAP-70 protein expression have been performed on whole blood samples (WBS), while some on lymph nodes (LN). The aim of our study was to examine if ZAP-70 protein expression in fine needle aspirates (FNAs) of LN is comparable to that in WBS and secondly, to evaluate ZAP-70 index prognostic value. We analysed ZAP-70 protein expression in 54 LN FNAs and 35 WBS of patients with CLL. In 21 cases, LN FNAs and WBS were from the same patient. ZAP-70 protein expression was determined by ZAP-70 index, calculated on the basis of ZAP-70 protein expression in CLL cells, B and T lymphocytes. ZAP-70 index was negative in 12/54 (22%) LN FNAs and 13/35 (37%) WBS, but positive in 42/54 (78%) LN FNAs and in 22/35 (63%) WBS. The clinical outcome seemed to be better in the group of patients with negative ZAP-70 index compared to those with positive ZAP-70 index. We found out that ZAP-70 indices were significantly higher in LN FNAs than in WBS. Our preliminary results showed that negative ZAP-70 index could have been associated with a favorable outcome of CLL and positive ZAP-70 index with a more aggressive disease. In our phase II study , 78 patients were treated by gemcitabine 250 mg/m2 in a 6-h infusion on days 1 and 8 and cisplatin at 75 mg/m2 on day 2 of a 3-week cycle for four cycles, followed by two additional cycles without cisplatin. 5% of patients showed a complete response and 45% showed a partial response. Minimal response or stable disease was seen in 45%, whereas only 5% patients progressed during treatment. Because of the acceptable toxicity, remarkable activity, and reasonable cost, this treatment should be further explored. Anaplastic thyroid carcinoma (ATC) may arise de novo or from a preexistent differentiated carcinoma. It is well known that higher iodine intake in the diet causes higher frequency of papillary thyroid carcinoma (PTC), but decreases the frequency of follicular thyroid carcinoma (FTC). However, it is not known how the change in iodine intake influences the frequency of ATC. A total of 205 patients with ATC (140 females, 65 males; median 69 years) were treated in the Republic of Slovenia between 1972 and 2008. In Slovenia, the salt was iodinated with 10 mg of potassium iodide/kg from 1972-1977. From 1998 to 2008 the degree of iodination of salt was increased to 25 mg of potassium iodide/kg. The frequency of ATC during the two periods and the characteristics of the patients during these periods were compared. The mean incidences of ATC during 1998-2008 and 1972-1997 was 6.2 (range 3-12) and 4 (range 2-10) patients per year, respectively. Our conclusion is that the incidence of ATC decreased after higher iodination of salt. Our findings suggest that iodine has an impact on tumor dedifferentiation.
Significance for the country
The achievements of our programme were from year 2009 to 2013 published as chapters or contributions in 33 monographic publications. Members of our programme group are authors of several professional and scientific papers published in international and Slovenian journals. Our findings were presented in many international and Slovenian professional and scientific meetings. This lead and contributed to better international recognition of Slovenia and enabled Slovenian researchers to integrate in the international scientific cooperation. In Slovenia, achievements of our programme were intergrated in a routine workup and more rational diagnostics and therapy of the patients. That contributed to improvement of provided quality of patients care. Members of our programme group are employed at the Medical Clinical Centre in Ljubljana and at the Institute of Oncology. On the basis of our findings and work, members of our programme change diagnostics and therapeutics algorithms (for example treatment of patients with breast carcinoma, malignant lymphoma,...). The reliability of diagnostic methods has improved in the field of leukemia, malignant lymphoma, plasmacytoma, soft tissue sarcoma and carcinoma of breast, thyroid, colon, cervical cancer, rectum and liver metastases. In former years, more accurate diagnosis of tumors enables more rational treatment of patients with target therapy (for example HER2 status in breast or gastric carcinoma), which improves the results of therapy. Members of our program group actively collaborate with researchers from other programs and projects in Slovenia and abroad. Members of our program group participated in the introduction of stem cell transplantation in the treatment of heart failure and the safe use of electrochemotherapy in liver tumors. In 2012, at the Department of Cytology of Institute of Oncology we began to use the new six-ink flow-cytometer. It is not surprising that the services of flow-cytometry laboratory is very useful for researchers from other research programs. The result of this work has been published in the journal Biomaterials in which one of co-authors was our researcher Jaka Lavrenčak. In the laboratory of department of pathology, we started to use tissue networks classifications for determination of HER2 expression in tumors of the stomach and gastroesophageal transition. This is clinically very useful, so in the future we expect intensification of research collaboration with surgeons from the University Medical Centre in Ljubljana.
Most important scientific results
Annual report
2009,
2010,
2011,
2012,
final report,
complete report on dLib.si
Most important socioeconomically and culturally relevant results
Annual report
2009,
2010,
2011,
2012,
final report,
complete report on dLib.si
