A rákmorbiditás és -mortalitás jelenlegi helyzete a Nemzeti Rákregiszter tükrében | The current situation of cancer morbidity and mortality in the light of the National Cancer Registry, Hungary

Absztrakt: A szerzők jelen folyóirat egy korábbi számában már ismertették és összefoglalták a hazai Nemzeti Rákregiszter alapvető célkitűzéseit és feladatát, nemzetközi környezetbe helyezve. Az újabb közlemény az előző folytatásának tekinthető, s az aktuális statisztikai adatok ismertetése és elemzése során vizsgálják azok népegészségügyi hátterét, a lehetséges kockázati tényezőkkel együtt. Az elmúlt évek változásai, a mortalitási adatokat illetően, stagnáló, enyhén hullámzó jelleget mutatnak, egyes lokalizációkat tekintve (például ajak és szájüreg, emlő, prosztata) azonban reménykeltő mutatókat lehet megfigyelni. Az összes daganatos halálozás alig változó jellegével szemben, az évi új bejelentett esetek száma jelentősen megemelkedett, amely a hatékonyabb diagnosztika és terápia szerepét egyaránt feltételezi. A fentiek tükrében megerősíthető, hogy a hazai onkológiai ellátórendszer szerkezetváltása s európai illeszkedése elkerülhetetlen. Orv. Hetil., 2017, 158(3), 84–89. | Abstract: In a previous issue of this journal the authors presented and summarized the basic objectives and tasks of the Hungarian National Cancer Registry positioned in an international environment. The recent publication is a continuation of the previous one. Based on the presentation and analysis of current statistical data, the public health background with the possible risk factors is examined. Considering changes in recent years, the mortality data are relatively stable, although slightly wavering. The trends are promising in some cancers (for example lip and oral cavity, breast, prostate cancers) however. Contrary to the barely changing nature of the total cancer deaths the number of annually reported new cases has increased significantly, which indicates a more effective role in both diagnostics and therapy. In light of the above, it is confirmed that the restructure of the national oncology care system and the European conformation is inevitable. Orv. Hetil., 2017, 158(3), 84–89

Inhibition of EGFR improves antitumor efficacy of vemurafenib in BRAF-mutant human melanoma in preclinical model

Background: Oncogenic activation of the epidermal growth factor receptor (EGFR) signaling pathway occurs in a variety tumour types, albeit in human melanoma the contribution of EGFR is still unclear. Methods: The potential role of EGFR was analyzed in four BRAF-mutant, one NRAS-mutant and one wild-type NRAS-BRAF-carrying human melanoma cell lines. We have tested clinically available reversible tyrosine kinase inhibitors (TKI) gefitinib and erlotinib, irreversible EGFR-TKI pelitinib and a reversible experimental compound (PD153035) on in vitro proliferation, apoptosis, migration as well as in vivo metastatic colonization in a spleen-liver model. Results: The presence of the intracellular domain of EGFR protein and its constitutive activity were demonstrated in all cell lines. We detected significant differences between the efficacies of EGFR-TKIs, irreversible inhibition had the strongest anti-tumour potential. Compared to BRAF-mutant cells, wild-type BRAF associated with relative resistance against gefitinib. In combination with gefitinib, selective mutant BRAF-inhibitor vemurafenib showed additive effect in BRAF-mutant cell lines. Treatment of BRAF-mutant cells with gefinib- or pelitinib attenuated in vitro cell migration and in vivo colonization. Conclusions: Our preclinical data suggest that EGFR is a potential target in the therapy of BRAF-mutant malignant melanoma; however, more benefits could be expected from irreversible EGFR-TKIs and combined treatment settings

A p16 tumorszuppresszor expressziójának prognosztikai szerepe magyarországi szájüregi laphámrákokban.

A fej-nyaki régió laphámrákjának legfontosabb rizikófaktorai az alkohol- és dohányexpozíció, illetve a humán papillómavírussal (HPV) való fertőzés, mely utóbbi alcsoport jóval kedvezőbb klinikai prognózist mutat. A p16 tumorszuppresszor sejten belüli szintje magas kockázatú HPV-fertőzés mellett megemelkedik, ami lehetőséget teremt arra, hogy molekuláris diagnosztikai módszerek helyett immunhisztokémia segítségével diagnosztizáljuk a fertőző ágens jelenlétét. A témában megjelent legtöbb kutatás a fej-nyaki régió egészére fókuszált, és nem kezelte külön a szájüregi lokalizációt. Munkánk során a szájüregi régióból műtétileg eltávolított 67 rosszindulatú laphámdaganat p16-expresszióját vizsgáltuk, és vetettük össze a fej-nyaki régióban rutinszerűen meghatározott klinikopatológiai paraméterekkel. A műtéti anyagokból tissue microarray (TMA) blokkokat készítettünk, majd immunhisztokémiai vizsgálat segítségével megvizsgáltuk a p16, illetve több más ismert molekuláris marker (p53, Ki67, EGFR) expresszióját. A fej-nyak régió laphámrákjait taglaló szakirodalmi adatokkal ellentétben saját szájüregi anyagunkban nem kaptunk összefüggést a fő klinikai paraméterekkel, a p16-pozitivitás csupán a recidíva tekintetében jelentett kedvező prognózist. A magi p53-pozitivitás főként a fiatalabb betegcsoportra volt jellemző. A p53- és az EGFR-expresszió statisztikailag szignifikáns korrelációt mutatott egymással. Megállapítottuk, hogy a fej-nyaki laphámrákokban alkalmazott molekuláris csoportosítás nem adaptálható teljes egészében a hazai szájüregi laphámrákokra. Felmerül az egyes etiológiai tényezők (HPV, dohányzás, alkohol) ko-expozíciós szerepe, ami megnehezíti az egyes kategóriák elkülönítését

Clinicopathological Features and Prognosis of Pregnancy Associated Breast Cancer – A Matched Case Control Study

Pregnancy Associated Breast Cancer (PABC) manifests during pregnancy or within a year following delivery. We sought to investigate differences in management, outcome, clinical, histopathology and immunohistochemistry (IHC) characteristics of PABC and matched controls in a retrospective case control study. PABC and control patients were selected from breast cancer cases of women </=45 years, diagnosed in the 2nd Department of Pathology, Semmelweis University, Budapest, Hungary between 1998 and 2012. Histopathology information on tumor type, grade, size, T, N, lympho-vascular invasion (LVI), Nottingham Prognostic Index (NPI), associated in situ lesions and IHC charcteristics: ER, PgR, HER2, Ki67, p53 were recorded, IHC-based subtype was assessed, clinical, management and outcome data were analysed. Thirty-one breast cancer cases were pregnancy related. Clinical management data did not differ in cases and controls. Histopathology of disease at presentation was not significantly different, but NPI assessed the PABC group as having poor, whereas controls as having intermediate prognosis. Associated in situ lesion was more often high grade Extensive Intraductal Carcinoma Component (EIC) in PABC. Triple negative and LuminalB prol tumors predominated in PABC. Disease-free and overall survival was inferior compared to controls. PABC patients with LuminalB prol and Triple negative tumors had inferior outcomes. On multivariate analysis inferior prognosis of PABC was associated with pregnancy. Our study has demonstrated inferior outcome of PABC. Difference in tumor biology is reflected by the predominance of triple negative and LuminalB tumors in PABC. The strength of the study is the analysis of complete pathology and IHC data

Prognostic impact of progesterone receptor expression in HER2-negative luminal B breast cancer

Aim: The new classification of breast cancer is based on microarray studies. Within the estrogen receptor (ER) positive breast carcinoma subtype further subgroups could be identified. In the present study, we analyzed the Her2 negative, highly proliferative subgroup (Luminal B1-like, LUMB1) with emphasis on their clinicopathological characteristics and progesterone receptor (PR) expression. Patients and methods: Our retrospective study concerned the period between 2000 and 2010. 158 patients were selected with ER positive, Her2 negative, Ki67>15% breast cancer. The pathological and clinical data were collected and analyzed. Age, tumor grade and stage, ER, PR, Her2 and Ki67 expression were recorded. The clinicopathological variables were correlated to PR expression. Results: The mean age of the patients was 57.5 (28-75) years. The ratio of patients younger than 40, was 8.86%. Shorter metastasis-free survival was observed in this young age group (P=0.044). The majority of our cases belonged to the pT1-pT2 stages (41.28% and 44.95%, respectively) whereas pT3 and T4 stage was detected in 5.50% and 8.25% of the cases, respectively. Almost half of the cases had no axillary lymph node metastasis (pN0: 48.91%), 1-3 lymph node metastases were detected in 38.04% (pN1), 4-10 metastatic lymph nodes were identified in 9.78% (pN2) and pN3 stage was found in 3.26% of the cases. Most commonly the tumors were either grade 2 or 3 (44.16% and 45%, respectively). The median value of Ki67 labeling index was 30%. Disease progression was detected in 36.19% of the patients. According to PR expression, a tendency to better prognosis (i.e. longer disease free- and overall survival) was detected in cases showing >10% PR positivity. However, no difference was found regarding tumor size, axillary stage, grade and age when comparing lower and higher PR expressing tumors. Conclusions: LUMB1 breast carcinomas are typically grade 2 and grade 3, the Ki67 labeling index is often 30% or higher. Distant metastases occur in more than one third of the cases. Within this subgroup, those cases with low PR expression represent a poor prognostic cohort. These findings require further investigations in larger number of LUMB1 breast cancer cases

Effectiveness and Waning of Protection With Different SARS-CoV-2 Primary and Booster Vaccines During the Delta Pandemic Wave in 2021 in Hungary (HUN-VE 3 Study)

BackgroundIn late 2021, the pandemic wave was dominated by the Delta SARS-CoV-2 variant in Hungary. Booster vaccines were offered for the vulnerable population starting from August 2021.MethodsThe nationwide HUN-VE 3 study examined the effectiveness and durability of primary immunization and single booster vaccinations in the prevention of SARS-CoV-2 infection, Covid-19 related hospitalization and mortality during the Delta wave, compared to an unvaccinated control population without prior SARS-CoV-2 infection.ResultsThe study population included 8,087,988 individuals who were 18–100 years old at the beginning of the pandemic. During the Delta wave, after adjusting for age, sex, calendar day, and chronic diseases, vaccine effectiveness (VE) of primary vaccination against registered SARS-CoV-2 infection was between 11% to 77% and 18% to 79% 14–120 days after primary immunization in the 16–64 and 65–100 years age cohort respectively, while it decreased to close to zero in the younger age group and around 40% or somewhat less in the elderly after 6 months for almost all vaccine types. In the population aged 65–100 years, we found high, 88.1%–92.5% adjusted effectiveness against Covid-19 infection after the Pfizer-BioNTech, and 92.2%–95.6% after the Moderna booster dose, while Sinopharm and Janssen booster doses provided 26.5%–75.3% and 72.9%–100.0% adjusted VE, respectively. Adjusted VE against Covid-19 related hospitalization was high within 14–120 days for Pfizer-BioNTech: 76.6%, Moderna: 83.8%, Sputnik-V: 78.3%, AstraZeneca: 73.8%, while modest for Sinopharm: 45.7% and Janssen: 26.4%. The waning of protection against Covid-19 related hospitalization was modest and booster vaccination with mRNA vaccines or the Janssen vaccine increased adjusted VE up to almost 100%, while the Sinopharm booster dose proved to be less effective. VE against Covid-19 related death after primary immunization was high or moderate: for Pfizer-BioNTech: 81.5%, Moderna: 93.2%, Sputnik-V: 100.0%, AstraZeneca: 84.8%, Sinopharm: 58.6%, Janssen: 53.3%). VE against this outcome also showed a moderate decline over time, while booster vaccine types restored effectiveness up to almost 100%, except for the Sinopharm booster.ConclusionsThe HUN-VE 3 study demonstrated waning VE with all vaccine types for all examined outcomes during the Delta wave and confirmed the outstanding benefit of booster vaccination with the mRNA or Janssen vaccines, and this is the first study to provide clear and comparable effectiveness results for six different vaccine types after primary immunization against severe during the Delta pandemic wave