[Immunoscore and Its Predictive Value for Colorectal Cancer]. / Immunoscore a jeho prediktivní hodnota u kolorektálního karcinomu.

Recent studies suggest that immune  classification (immune-score) in cancer patients has a prognostic value in some cases that seems to be superior to the AJCC/ UICC TNM  classification. The clinical outcome can vary significantly among patients with a particular diagnosis within the same TNM stage. Immunoscore methodology quantifies and detects different types of immune cells in tumor tissue, and also determines the density of their infiltration and localization at the tumor site. Currently within an international collaboration of 23 centers in 17 countries (including our department), immunoscore is being evaluated in more than 7,000 colorectal cancer patients in terms of the tumor microenvironment, focusing on the presence of immune cells both in the tumor tissue and the tumor invasive margin. Immunoscore results are assessed in correlation with: 1. patients response to the treatment, 2. rate of progression, disease prognosis and other immune parameters. It appears that the TNM classification and tumor invasiveness is statistically dependent on the immune response of the patient (there is an inverse correlation between the density of the infiltration of CD8⁺, CD3⁺ lymphocytes and the tumor stage). High densities of T-lymphocytes (CD8⁺, CD3⁺) both in the core and the invasive margin of the primary tumor are associated with longer term asymptomatic survival, overall survival, lower risk of relapse and reduced likelihood of metastases. The project of the international collaboration aims to introduce immunoscore in routine diagnostics.

Cellular and humoral immunodeficiency in breast cancer patients resistant to hormone therapy.

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.

Mutations of the BRCA1 gene in hereditary breast and ovarian cancer in the Czech Republic.

OBJECTIVE: Mutations in the BRCA1 gene confer a high risk for the development of breast or ovarian cancer. The aim of this study was to establish the frequency and spectrum of BRCA1 mutations in Czech breast or ovarian cancer families. SUBJECTS AND METHODS: We have screened 28 patients with early-onset cancer and 54 patients from risk families for germ-line mutations in BRCA1. All coding exons were analyzed by the protein truncation test (PTT) and the reverse transcription polymerase chain reaction (RT-PCR). Detected variants were characterized by direct sequencing of PCR products. RESULTS: Five distinct deleterious mutations have been identified in six families. All the mutations led to the premature termination of translation. One mutation was detected in a group of 11 (9.1%) patients with early-onset breast cancer. Two mutations were observed in 32 (6.3%) families with a history of breast cancer only. Three mutations were found in 22 (13.6%) families with both breast and ovarian cancer. The 5382insC mutation was the only abnormality detected twice. In addition, two variant transcripts, the loss of exon 5 and in-frame 3-bp deletion at the beginning of exon 8, were identified only at the cDNA level. Their biological significance remains unknown. CONCLUSION: PTT analysis enables examination of long PCR products. The technique is useful for rapid detection of mutations in hereditary breast cancer.

[Cervical carcinoma during pregnancy]. / Cervikální karcinom v tehotenství.

OBJECTIVE: To evaluate management and outcome of pregnant women with cervical carcinoma. DESIGN: Retrospective clinical study. SETTING: Institute for Mother and Child Care, Prague, Czech Republic. METHODS: Clinical data of pregnant women suffering from cervical carcinoma were summarized and assessed. The primary treatment was radical hysterectomy and pelvic lymphadenectomy including the foetus in utero in the first and early second trimester and caesarean section and radical surgery after viability of the foetus has been reached. Patients were assessed with regard to the stage of the disease and the stage of pregnancy. RESULTS: In this retrospective study we discuss 8 cases of cervical cancer diagnosed during pregnancy. According to the TNM classification 3 patients were in stage Ib1, 3 patients in stage Ib2, one patient in stage IIa and one patient in stage IIb. With the exception of one patient in stage IIb all cases were operable with no complication after radical surgery. After a follow-up of at least 12 months we are convinced that pregnancy has no negative effect on the prognosis of cervical cancer.

[A large metastasis of colorectal carcinoma--case report]. / Velká metastáza kolorektálního karcinomu--kazuistika.

The authors present the case-history of a female patient four years after a low resection on account of carcinoma of the rectum who developed a large secondary in the abdominal wall. After its radical resection the patient is free from systemic or local manifestations of the basic disease and free from complaints.

[Conservative surgical treatment of breast carcinoma in women from the viewpoint of the oncologist-radiotherapist]. / Konzervativní chirurgická lécba karcinomu prsu zen z pohledu klinického onkologa-radioterapeuta.

The authors draw attention to the changed approach to treatment of initial stages of breast in women--a change from radical mastectomy to less radical operations supplemented by radiotherapy or possibly systemic treatment. They analyze in detail the prerequisites and results of this procedure and demonstrate their conclusions on a group of 27 women.

[Prognostic factors in non-Hodgkin's malignant lymphoma]. / Prognostické faktory u nehodgkinských maligních lymfomu.

A group of 271 patients with non-Hodgkin's malignant lymphomas from years 1975-1989 was tested using multivariant statistical analysis, from the point of view of the prognostic value their basic clinical and laboratory data. In the group of low grade malignancy lymphomas, the following factors showed a prognostic validity: clinical stage, general status, centrocytic histological subtype, and anaemia. In the group of high grade malignant lymphomas following one were set as prognostically important: general status, clinical stage and age. In particular histological subtypes of low grade malignancy statistically valid difference of survival was not proved, the centrocytic type excluded. However, the difference was found between these types and particular subtypes of high malignancy grade. Based on these results, the Cox's risk model was made, enabling us to define 4 risk groups according to the histological subtype and clinical stage: group A (risk less than 0.5), group B (risk = 0.5-1.0), group C (risk = 1.0-2.0), group D (risk greater than 2.0).