Correlation with lymphocyte infiltration, but lack of prognostic significance of MECA-79-positive high endothelial venules in primary malignant melanoma.

High endothelial venules (HEVs) are specialized vessels in lymphoid organs, supporting lymphocyte trafficking from the blood. As the presence of these vessels was described recently in tumors, it was proposed that they could facilitate the development of antitumor immune response, resulting in improved prognosis. The aim of our study was to analyze the correlation of the density of HEVs with that of the different immune cell types as well as with the clinicopathologic parameters and the disease outcomes in patients with cutaneous melanoma. Primary melanoma samples of 118 patients were analyzed retrospectively by immunohistochemical labeling and quantitation of vessels stained with the MECA-79 antibody, as well as a panel of eight different immune cell types (CD8 and CD45RO T cells, lymphocytes expressing the CD25, CD134, or CD137 activation markers, FOXP3 regulatory T cells, CD20 B cells, and DC-LAMP mature dendritic cells). Correlations of MECA-79 vessel density with that of the immune cells, as well as with clinicopathologic parameters and disease outcomes were evaluated. We showed that the number of MECA-79 vessels correlates strongly with the peritumoral density of B and T lymphocytes. Moreover, higher HEV numbers were detected in tumors hosting tertiary lymphoid structures as well as in those of axial location compared with the ones in the extremity and in men compared with women, whereas no association was found with patient age, tumor thickness, histologic type or ulceration, or with the survival of melanoma patients. The density of MECA-79 HEVs in primary melanomas shows a correlation with B and T-lymphocyte density and differences according to the presence of tertiary lymphoid structures, tumor site, and the sex of the patient. However, it has no prognostic value.

Tumor-infiltrating immune cells as potential biomarkers predicting response to treatment and survival in patients with metastatic melanoma receiving ipilimumab therapy.

Monoclonal antibodies targeting immune checkpoints are gaining ground in the treatment of melanoma and other cancers, and considerable effort is made to identify biomarkers predicting the efficacy of these therapies. Our retrospective study was performed on surgical tissue samples (52 lymph nodes and 34 cutaneous/subcutaneous metastases) from 30 patients with metastatic melanoma treated with ipilimumab. Using a panel of 11 antibodies against different immune cell types, intratumoral immune cell densities were determined and evaluated in relation to response to ipilimumab treatment and disease outcome. For most markers studied, median immune cell densities were at least two times higher in lymph node metastases compared to skin/subcutaneous ones; therefore, the prognostic and predictive associations of immune cell infiltration were evaluated separately in the two groups of metastases as well as in all samples as a whole. Higher prevalence of several immune cell types was seen in lymph node metastases of the responders compared to non-responders, particularly FOXP3+ cells and CD8+ T lymphocytes. In subcutaneous or cutaneous metastases, on the other hand, significant difference could be observed only in the case of CD16 and CD68. Associations of labeled cell densities with survival were also found for most cell types studied in nodal metastases, and for CD16+ and CD68+ cells in skin/s.c. metastatic cases. Our results corroborate the previous findings suggesting an association between an immunologically active tumor microenvironment and response to ipilimumab treatment, and propose new potential biomarkers for predicting treatment efficacy and disease outcome.

Immune cell profile of sentinel lymph nodes in patients with malignant melanoma - FOXP3+ cell density in cases with positive sentinel node status is associated with unfavorable clinical outcome.

BACKGROUND: Besides being a preferential site of early metastasis, the sentinel lymph node (SLN) is also a privileged site of T-cell priming, and may thus be an appropriate target for investigating cell types involved in antitumor immune reactions. METHODS: In this retrospective study we determined the prevalence of OX40+ activated T lymphocytes, FOXP3+ (forkhead box P3) regulatory T cells, DC-LAMP+ (dendritic cell-lysosomal associated membrane protein) mature dendritic cells (DCs) and CD123+ plasmacytoid DCs by immunohistochemistry in 100 SLNs from 60 melanoma patients. Density values of each cell type in SLNs were compared to those in non-sentinel nodes obtained from block dissections (n = 37), and analyzed with regard to associations with clinicopathological parameters and disease outcome. RESULTS: Sentinel nodes showed elevated amount of all cell types studied in comparison to non-sentinel nodes. Metastatic SLNs had higher density of OX40+ lymphocytes compared to tumor-negative nodes, while no significant difference was observed in the case of the other cell types studied. In patients with positive sentinel node status, high amount of FOXP3+ cells in SLNs was associated with shorter progression-free (P = 0.0011) and overall survival (P = 0.0014), while no significant correlation was found in the case of sentinel-negative patients. The density of OX40+, CD123+ or DC-LAMP+ cells did not show significant association with the outcome of the disease. CONCLUSIONS: Taken together, our results are compatible with the hypothesis of functional competence of sentinel lymph nodes based on the prevalence of the studied immune cells. The density of FOXP3+ lymphocytes showed association with progression and survival in patients with positive SLN status, while the other immune markers studied did not prove of prognostic importance. These results, together with our previous findings on the prognostic value of activated T cells and mature DCs infiltrating primary melanomas, suggest that immune activation-associated markers in the primary tumor may have a higher impact than those in SLNs on the prognosis of the patients. On the other hand, FOXP3+ cell density in SLNs, but not in the primary tumor, was found predictive of disease outcome in melanoma patients.

Melanoma screening in a hungarian nuclear power plant.

The industrial use of the ionizing radiation (IR) particularly stresses the safe work, regular health control is inevitable. Since previous occupational cohorts reported contradictory data on the incidence of melanoma among nuclear industry workers, and in few publications significant increase of it has been described, our clinic was requested by the industry to screen malignant skin tumours among the workers of a power plant. Within a year we have investigated 556 workers, 275 females and 281 males. Out of them 283, majorly males had been officially confirmed as to be employed at hazardous, but strictly controlled environment for an average of 18 years (1-32 years). To distinguish between IR and environmental UV (UVA+UVB) induced cutaneous malignancies we determined the sun and tanning bed exposure of the workers. One in situ melanoma developed in a woman with type I skin, bullous sunburns in the history, who had worked in safe environment for 26 years. Basal cell carcinoma was identified in two men, each of them worked for more than 20 years with IR (in hazardous environment). One had type I skin, the other had type II skin. These results didn't differ significantly (chi-squared test; p = 0, 2437 and 1, 0) from the national population data and the results of Euromelanoma screening campaign in Hungary. Our data clearly show, that 1./UV exposure and skin type should be evaluated in occupation cohort studies. 2./The melanoma incidence was not significantly higher among the employees of the power plant than in the general Hungarian population, according to the results of our study, the only Hungarian power plant is safe as far as the skin carcinogenesis is concerned.

Prognostic impact of B-cell density in cutaneous melanoma.

Studies on the prognostic importance of tumor-infiltrating lymphocytes have mainly focused on T cells, while little is known about the role of tumor-infiltrating B lymphocytes. We investigated the prevalence of CD20(+) B cells by immunohistochemistry in primary melanoma samples of 106 patients and analyzed in relation to clinicopathological parameters and patients' survival. The majority of samples contained a significant amount of B lymphocytes, predominantly dispersed in the stroma surrounding tumor deposits (mean peritumoral and intratumoral densities: 178.7 ± 156.1 vs. 4.9 ± 6.9 cells/mm², respectively). B cells organized in follicle-like aggregates were also observed in 26% of the samples. B-cell density correlated with that of activated (CD25(+) or OX40(+)) T lymphocytes. Infiltration by CD20(+) lymphocytes did not correlate with tumor thickness, while the presence of B-cell aggregates was observed more frequently in thick melanomas. On the other hand, B-cell infiltration was more pronounced in nonmetastatic or lymph node metastatic tumors, compared to visceral metastatic ones. Accordingly, high number of these cells provided significant survival advantage (P = 0.0391 and P = 0.0136 for intra- and peritumoral infiltration, respectively). Furthermore, combination of peritumoral B-cell density with the number of activated T lymphocytes identified patient subgroups with different disease outcome, which was most favorable in the case of high density, while very poor in the case of low density of both cell types. Multivariate survival analysis identified tumor thickness and CD20(+)/OX40(+) cell density combination as significant independent prognostic factors. Taken together, our results show correlation between low number of CD20(+) B lymphocytes and melanoma progression, indicating a possible role of tumor-infiltrating B cells in antitumoral immune response. It was also reflected in better outcome of the disease since the density of B lymphocytes alone as well as in combination with that of activated T cells proved of prognostic importance in patients with malignant melanoma.

[Standard CHOP immuno-chemotherapy for primary mediastinal lymphomas]. / A primer mediastinalis lymphomák standard R-CHOP immun-kemoterápiás kezelése.

INTRODUCTION: Primary mediastinal lymphoma (PMBCL) is an aggressive diffuse large B-cell lymphoma entity. It is a rare disease with specific clinical symptoms. The tumor is predominantly localized in the mediastinum but grows rapidly and infiltrates the surrounding tissues and organs. Two thirds of the patients are young females. Previous studies showed that third generation treatments are more effective than former standard cyclophosphamide-doxorubicin-vincristine-prednisolone (CHOP) regimens. AIM: Authors' goal was to assess whether adding the anti-CD20 monoclonal antibody, rituximab to the standard CHOP regimen improves the efficacy of the treatment compared to their previous results with CHOP and third generation chemotherapy regimens. METHODS: Between October, 2002 and December, 2004 they have started the rituximab-CHOP (R-CHOP) treatment of 20 newly diagnosed, previously untreated PMBCL patients. Results were compared to the data of 24 patients receiving CHOP (n = 9) or procarbazin-prednisolone-doxorubicin-cyclophosphamide-etoposide-cytosin-arabinoside-bleomycin-vincristin-methotrexate (ProMACE-CytaBOM) (n = 15) treatment in the past. RESULTS: During an average follow-up of 64.6 months, the 5-year overall survival (OS) rate was significantly higher in the R-CHOP group compared to the CHOP treatment (79.4% vs. 33.3%; p = 0.026). However, due to the low number of cases, significant statistical difference could not be demonstrated in the 5-year event-free survival (EFS: 70.0% vs. 33.3%; p>0.05), disease-free survival (DFS: 70.0% vs. 33.3%; p>0.05) and relapse-free survival rate (RFS: 93.0% vs. 100%; p> 0.05), despite of the remarkable numeric difference. When comparing the 5-year survival rates of R-CHOP and ProMACE-CytaBOM treatments, the results were very similar without any significant statistical difference between the two types of treatment (OS: 79.4% vs. 80%; EFS: 70.0% vs. 60.0%; DFS: 70.0% vs. 60.0%; RFS: 93.0% vs. 82.0%; p> 0.05 in all cases). With adding rituximab to CHOP treatment, which was previously considered an insufficient treatment on its own, authors have obtained as good results in treating PMBCL as with third generation regimens. Patients have received the R-CHOP treatments without major side effects and mainly as out-patients. CONCLUSIONS: Standard R-CHOP treatment could therefore replace the more toxic third generation regimens in PMBCL as well. The data are comparable with those reported in the international literature.

FOXP3+ cell density in primary tumor has no prognostic impact in patients with cutaneous malignant melanoma.

Regulatory T cells (Tregs) have been implicated as inhibitors of antitumor immune reactions. However, data on the relevance of their prevalence at tumor sites in influencing disease outcome are controversial. The aim of our study was to investigate the role in tumor progression and the prognostic impact of the density of lymphocytes expressing FOXP3, a transcription factor expressed predominantly by CD4(+)CD25(+) Tregs, in primary cutaneous melanoma. We examined the infiltration of FOXP3(+) cells by immunohistochemistry in tumor samples from 97 patients and evaluated in relation to patient and tumor parameters. The degree of infiltration by FOXP3(+) cells did not show correlation with the thickness of melanomas. Moreover, no associations were found with metastasis formation during the 5-year follow-up period, patient survival, or any other clinicopathologic parameters studied. These results suggest that the presence of FOXP3(+) lymphocytes in primary tumors is not of prognostic importance in human cutaneous melanoma.

[Results of immuno-chemotherapeutic treatment of patients with diffuse large B-cell lymphoma]. / Diffúz nagy B-sejtes lymphomák immunokemoterápiás kezelésével elért eredményeink.

Treatment with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) has been considered as the standard therapy for diffuse large B-cell lymphoma (DLBCL) for more than 20 years. CHOP treatment in combination with targeted immunotherapy, rituximab (R-CHOP), resulted in significant improvements in the treatment of this group of patients. In this study, efficacy of R-CHOP and R-CHOP-like treatments was analysed. Results were compared to the data of historical patients only receiving CHOP treatment or CHOP-like treatment. Between September 2002 and April 2005, 140 newly diagnosed, untreated DLBCL patients started to receive R-CHOP treatment in a single centre. The eligibility criteria included advanced stage (clinical stages III-IV), or large tumour size (>7 cm) and/or symptom B or extranodal manifestation in the case of clinical stages I-II. The results were compared to the data of 130 patients only receiving CHOP treatment in the past. In the patients receiving R-CHOP, the therapeutic outcomes were superior for all parameters. During an average follow-up period of 44 or 52 months, the overall remission rate was 73.6% in the R-CHOP group in comparison with 47.7% in the CHOP group. The 5-year overall survival was 68.6% vs. 41.0% (RR: 0.4293, CI: 0.2963-0.6221; p < 0.0001), the event-free survival was 59.8% vs. 33.5% (RR: 0.5038, CI: 0.3606-0.7038; p < 0.0001) and the progression-free survival was 64.4% vs. 37.6% (RR: 0.4915, CI: 0.3442-0.7019; p < 0.0001). Since prognostic parameters were more favourable in the R-CHOP group, patient groups were also compared using the International Prognostic Index score. Again, significant differences were revealed by the subgroup analyses. The 5-year overall survival was 74.4% vs. 47.9% (RR: 0.4475, CI: 0.2418-0.8285; p = 0.0084) and 52.0% vs. 28.8% (RR: 0.4989, CI: 0.3098-0.8035; p = 0.003) in the group with good prognosis and in the group with poor prognosis, respectively. In the group with very good prognosis, the statistical difference between the two groups in terms of the 5-year survival parameters remained undetectable as a result of the already very high therapeutic effect and low case number (OS and EFS: CHOP: 100% and 62.5% vs. R-CHOP: 90.9% and 87.0%; p = 0.3873 and p = 0.1702). Combining the standard CHOP treatment with rituximab resulted in a significant improvement of the therapeutic outcomes irrespective of the prognostic grouping. The data are comparable with those reported in the international literature.

[Survival chances of Hungarian cancer patients in the National Cancer Registry]. / A magyar daganatos betegek túlélési esélye a Nemzeti Rákregiszter adatai alapján.

The Hungarian National Cancer Registry (HNCR) was launched in August, 1999 by the National Cancer Institute. The main goal of HNCR is to determine the prevalence of different types of malignant cancers. A new method, period analysis was invented to determine survival chances of patients with malignant tumor. Based on period analysis we developed a new method by approximating survivals of Hungarian cancer patients with the help of Gompertz distribution. Our survival analysis was based on HNCR data of patients with cancer recognized between January 1, 2002 and December 31, 2005. These data are far enough from the time when HNCR started, thus they do not contain the initial errors, but also far enough from the present so their correction could be considered completed. In case of 21 malignant tumor locations for males and 23 ones for females we determined the parameters of the Gompertz distribution and based on the estimated parameters we estimated the expected survival probabilities for each specific tumor type and gender. In this study we have not used the TNM-based clinical stage or any other data of the patients contained by HNCR. Using the Gompertz model, the complete recovery of a cancer patient is always possible and the probability of recovery has a reliable estimate based on a short follow-up period only. We compared our results with five-year survival data of Canada, Italy, Norway and Finland and we did not find substantial differences. For both men and women, considering any specific location, the differences in survival among countries are much smaller than the difference between locations.

Increase of hypophyseal hormone levels in male head and neck cancer patients.

Head and neck squamous cell carcinoma (HNSCC) develops in at least 80% of cases in men with a history of smoking and heavy alcohol consumption, still it is only diagnosed in a small proportion of alcoholics. Endocrine milieu is an important factor in carcinogenesis and prognosis of several cancer types. The aim of our study was to investigate sex steroid and hypophyseal hormone status of male HNSCC patients in comparison to healthy volunteers and to patients with alcoholic liver disease, to determine possible hormonal alterations characteristic of cancer. Liver function (GGT level), and serum levels of gonadotropic hormones (FSH, LH, prolactin), sex steroids (estradiol, progesterone, testosterone) and sex hormone-binding globulin (SHBG) were compared in 130 male HNSCC patients, 54 patients with alcoholic liver disease but no known cancer, and 56 healthy controls. We found abnormal values of liver function in both HNSCC patients and alcoholics compared to healthy controls, suggesting the presence of alcoholic liver disease in the former group as well. On the other hand, a significant elevation in the level of DHEA, FSH and LH was observed in cancer patients exclusively. As a conclusion, abnormal alterations in sex steroid hormone levels can frequently be found in HNSCC patients, which may be caused in part by the alcoholic liver damage accompanying the disease. The significant increase in FSH and LH serum levels, observed only in the cancer patients, indicates that these hormones may play a role in the development and/or progression of HNSCC.

Association of microvessel density with infiltrating cells in human cutaneous malignant melanoma.

Vascularization and host response to malignant tumors may have common molecular regulators, therefore, we analyzed the relationship between microvessel density (MVD) and tumor infiltrating cells in cutaneous malignant melanoma. Density of lymphocyte subpopulations, macrophages, dendritic cells and CD34(+) microvessels was determined by immunohistochemistry in primary tumor samples from fifty-two patients with melanoma thicker than 1 mm. Intratumoral MVD did not show significant association with infiltration for any of these cell types. In the case of peritumoral reactive cell densities analyzed in the whole patient population, a positive correlation of MVD was found with CD3(+) T cell density. This association was stronger in melanomas >4.0 mm and in visceral metastatic tumors. In these subgroups similar phenomenon was observed for CD8(+) cells. We found significant correlation of MVD with CD68(+) macrophage density only in the highest thickness category, and weak associations with B-cell and dendritic cell infiltration in visceral metastatic cases. MVD did not vary significantly in tumors categorized according to thickness, localization, ulceration or histological type. However, both intratumoral MVD and macrophage infiltration were significantly higher in male patients compared to females. The correlation of immune cell density with tumor vascularization and gender differences in vascularity and macrophage infiltration of melanoma deserve further attention.

Density of DC-LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor.

As the most potent antigen presenting cells, dendritic cells (DCs) play key roles in the immune response against tumors. Their density in the tumor tissue has been associated with prognosis in patients with various cancers. However, few studies have been aimed at the presence and maturation state of DCs in cutaneous melanoma, with regard to their potential clinical correlates. In this study, the density of DCs expressing CD1a and the maturation marker DC-LAMP was determined by immunohistochemistry in primary tumor samples from 82 patients with cutaneous malignant melanoma. Intratumoral and peritumoral cell densities were analyzed in relation to tumor thickness and the subsequent development of metastases, as well as to patients' survival. CD1a(+) DCs were found both infiltrating melanoma cell nests and in the surrounding stroma, while DC-LAMP(+) mature DCs were generally confined to the peritumoral areas, associated with lymphocytic infiltrates. DC density values significantly correlated with the number of activated (CD25(+) or OX40(+)) T lymphocytes (p < 0.001). The degree of infiltration by CD1a(+) and DC-LAMP(+) DCs showed strong inverse correlation with the thickness of melanomas (p < 0.001). High peritumoral density of mature DCs was associated with significantly longer survival (p = 0.0195), while density of CD1a(+) cells had a prognostic impact of borderline significance (p = 0.0610). Moreover, combination of high peritumoral CD1a(+) or DC-LAMP(+) cell density with high number of CD25(+) or OX40(+) lymphocytes identified patient subgroups with more favorable survival compared to other subgroups. A multivariate survival analysis involving DC and activated T-cell densities alone and in combinations, as well as traditional prognostic factors, identified high DC-LAMP(+) cell/high OX40(+) cell density and Breslow index as independent predictors of good prognosis. These results suggest that the presence of CD1a(+) DCs primarily depends on the thickness of melanomas, without direct relationship with the patients' survival. On the other hand, the density of mature DCs, especially in association with that of activated T cells, proved of prognostic importance, suggesting that these parameters could be considered as signs of a functional immune response associated with better outcome of the disease.

[An interdisciplinary malignancy, the lung cancer in Hungary in 2006: epidemiology, prevention and access to therapy]. / Egy interdiszciplináris betegség, a tüdorák Magyarországon 2006-ban: epidemiológia, megelozés és terápiás esélyegyenloség.

The most frequent malignant tumor is lung cancer all around the world. Mortality rate is highest in Hungary. The frequency accumulates in the Southern part of the country. Early radical resection is the really effective treatment of the disease, which can bring the chance of longer survival. The methods of prevention, such as restrain of smoking and early detection with targeted examinations of the risk groups need more attention. There are unacceptable differences among regions in Hungary on the field of the accessibility to the adequate therapies. There are three-fold differences in the rate of operation and radiotherapy between certain counties. The frequency of the chemotherapy is acceptable, but there are some centers which do not use the recommended modern protocols. Professional supervisors and inspectors must give marked attention to the quality control of lung cancer therapies to provide equal chances to patients, independently of their residence.

[Detection of late ototoxic side effect of cisplatin by distortion otoacoustic emission (DPOAE)]. / Ciszplatinnal kezelt heretumoros betegek késôi halláskárosodásának vizsgálata disztorziós otoakusztikus emissziós (DOAE) készülékkel.

Cisplatin-based chemotherapy results in high cure rate in testicular cancer. The issue of toxicity is of special concern in young men with a probability of cure of at least 70-80% even in disseminated disease. As the literature shows, the ototoxic side effects of cisplatin have been studied mostly by conventional method. The authors used distortion product otoacoustic emission to detect the long-term ototoxic effect of cisplatin in 223 patients with a median follow-up time of 4.27 years (range 0.5-20 years) and a median age of 37 years (range 18-55 years). Cisplatin (20 mg/m(2) body surface) was administered for five days per cycle, in combination with other antitumor drugs. The control group consisted of 40 testicular cancer patients who did not receive chemotherapy, with a median age of 35 years (range 16-54 years). A detailed medical history based on a standardized questionnaire evaluated hearing complaints and audiological risk factors, such as head injuries, chronic otitis media, previous noise exposure and familial hearing loss. DPOAE was measured at 8 frequencies from 750 to 8000 Hz. No amplitude changes were detected in patients receiving =300 mg/m(2) cisplatin. At higher doses, contrary to the literature, not only high frequencies were affected: our method could detect significant hearing impairment at lower frequencies important for speech perception in patients receiving at least 400 mg/m(2) cisplatin. The lower frequencies where significant amplitude changes were detected were 3000 Hz at 400 mg/m(2), and 1500, 2000 and 3000 Hz at 500-600 mg/m(2). We detected the worst hearing in the case of patients who had symptomatic ototoxicity. Age and the cumulative dose of cisplatin proved statistically significant risk factors, while smoking or noise exposure did not have predictive value. As a conclusion, DPOAE is a fast, noninvasive and reliable method for the detection of late ototoxicity in testicular cancer patients. In our study hearing loss correlated with the cumulative dose of cisplatin. Hearing impairment contributes to the already compromised situation of cancer patients.

T-cell activation marker expression on tumor-infiltrating lymphocytes as prognostic factor in cutaneous malignant melanoma.

The central role of T cells in antitumor immunity is well established. However, tumor progression, often seen in the presence of substantial lymphocytic infiltration, suggests that these T cells are not capable of mounting an effective immune response to control tumor growth. Evidence has accumulated that T lymphocytes infiltrating human neoplasms are functionally defective, incompletely activated, or anergic. Therefore, when characterizing the immune competent cells within lymphoid infiltrates of tumors, it is important to assess their activation state. We investigated the expression of two T-cell activation markers, interleukin 2 receptor alpha (CD25) and OX40 (CD134), by immunohistochemistry in primary cutaneous melanoma samples of 76 patients and analyzed it in relation to tumor stage and tumor progression (>5 years follow-up), as well as to patients' survival. We found that the degree of infiltration by CD25(+) and intratumoral OX40(+) lymphocytes showed a tendency to decrease in thicker melanomas. The frequency of samples with high numbers of peritumoral CD25(+) and OX40(+) cells was significantly lower (P = 0.0009 and P = 0.0087, respectively) in melanomas developing distant visceral metastases, compared with nonmetastatic or lymph node metastatic tumors. For both activation markers studied, high peritumoral densities were associated with longer survival by univariate analysis (P = 0.0028 and P = 0.0255 for CD25 and OX40, respectively), whereas peritumoral OX40(+) lymphocyte infiltration had an impact on survival also in multivariate analysis (P = 0.035). The results suggest that the presence of lymphocytes expressing the T-cell activation markers CD25 or OX40 shows correlation with tumor progression as well as with patients' survival in cutaneous malignant melanoma.

[Treatment of primary mediastinal large B-cell lymphomas]. / Primer mediasztinalis nagy B-sejtes lymphomák kezelése.

INTRODUCTION: Primary mediastinal large B-cell non-Hodgkin's lymphoma is a relatively rare disease with specific clinical symptoms. This tumour originates from a subset of B-cells of the thymus and at the time of the diagnosis the disease is predominantly localised in the mediastinum. The tumor grows rapidly and frequently involves other thoracic structures. The majority of the patients are young females. There are no histologic features that reliably distinguish these tumors from other diffuse large B-cell lymphomas. This is the only lymphoma subtype which can only be defined by the combination of clinical and pathologic features. Analysis with DNA microarrays verified that primary mediastinal and diffuse large B-cell lymphomas are different diseases. AIMS: Comparing the effectiveness of two types of anthracycline-based standard chemotherapy regimens and the evaluation of the prognostic markers which are applied in large B-cell lymphomas. METHODS: 27 patients with primary mediastinal lymphoma were treated by the authors with anthracycline-based polychemotherapy with complementary radiotherapy from January 1995 to December 2002. RESULTS: Complete remission was obtained in 15 patients (56%) and no relapse was observed in this group. 9 additional patients (33%) achieved partial remission, while in 3 cases (11%) the treatment was ineffective. The patients who failed to achieve complete remission were subsequently treated with more intensive chemotherapy. Afterwards, those patients who were chemosensitive, underwent high-dose chemotherapy with autologous peripheral blood stem-cell transplantation. The chemoresistant patients received palliative chemotherapy. The 5-year overall survival rate of the 27 patients was 62.11%. CONCLUSION: The authors found that the procarbazine, prednisolone, adriamycin, cyclophosphamide, etoposide, cytosine-arabinoside, bleomycin, vincristine, methotrexate treatment was more effective than the cyclophosphamide, adriamycin, vincristine, prednisolone combination. The expected 5-year overall survival rates were 83.57% vs. 33.33%, respectively. This difference was significant (p = 0.017). No prognostic value of age adjusted international prognostic index, LDH- and b2-microglobulin levels were found. The results with the new standard of combined immuno-chemotherapy (rituximab--cyclophosphamide, adriamycin, vincristine, prednisolone) seem to be hopeful and more effective than earlier treatments.

[Prognostic significance of sex steroid and hypophyseal hormones in head and neck squamous cell carcinoma]. / Szex szteroid- és hypophysishormonszintek prognosztikus jelentôsége fej-nyaki laphámrákban.

OBJECTIVE OF THE STUDY: to investigate the clinical outcome of HNSCC patients, and their hormonal status. METHOD: The liver function (GGT), hypophysis gonadotrop hormone (FSH, LH, prolactin) and sexsteroid hormone serum levels were examined in 130 male HNSCC patients. Clinical parameters for age, primary tumor site and clinical tumor stage were also recorded. RESULTS: The survival was disadvantageously influenced by the following parameters: age, the presence of lymph node metastasis, advanced tumor stage, the lower than normal testosterone and the higher than normal FSH serum levels. CONCLUSION: Elevated FSH and decreased testosterone serum levels showed significant correlation with the survival of head and neck cancer patients. The better understanding of their exact role in the biology of HNSCC requires further investigations.

[New cases of melanoma as documented in the National Cancer Registry]. / Melanomás megbetegedések a Nemzeti Rákregiszter alapján.

The authors briefly survey general aspects of crucial importance for the proper functioning of the National Cancer Registry, such as legislation, collected data, identification of patients, the completeness and validity of its content in relation to the results and conclusions of a comprehensive, national supervision performed after the Melanoma Consensus Conference. Compared to earlier national controlling attempts, the present supervision was highly successful: doctors of various hospitals did perform the detailed control of diagnosis in 95.81% of 1361 melanoma patients announced in 2001. They checked whether patients given the C43 BNO code had melanoma indeed, searched for those who received a different BNO code and identified those not announced for any reason to the Registry. After correction the Registry included 1117 new cases of melanoma in 2001. The authors state that the conclusions from this supervision may enhance the reliability not only of the data base of the Registry but that of the hospitals as well.

[The course of cancer mortality in Hungary between 1975 and 2001]. / A rosszindulatú daganatos halálozás változása 1975 és 2001 között Magyarországon.

The course of cancer mortality in this country between 1975 and 2001 was analysed solely with mathematical methods using the mortality data provided by the Central Statistical Office. Mortality data were studied according to patient s sex and tumour localisation and in relation to total cancer mortality. The increase and decrease in cancer mortality were found to differ by sex and tumour localisation: e.g. death rate caused by cancers of the oral cavity showed low deviation with an even increase just like the mortality caused by colorectal cancer, the latter, however, was steeper with men. In case of melanoma higher deviation was associated with increased mortality, again at a higher rate with men. Dying of testicular cancer and of gastric cancer in either sex showed decreasing tendencies. Lung cancer mortality assumed different patterns in the two genders: with men it kept increasing at an even pace until 1994 then the increase stopped. With women, however, the increase since 1985 was steeper than earlier. The breast cancer mortality rates can also be divided into two periods. There was an even rise until 1994 followed by stagnation. As to the total cancer mortality values, the authors state that the rhythm of increase during the first 20 years of the study period had changed, the steepness of trends in the last seven years can be expressed in a small positive number not differing from zero at significant level which means that the increase in cancer mortality has stopped.