Ovarian clear cell carcinoma (OCCC) is a subtype of ovarian carcinoma characterized by unique biological features and highly malignant characteristics including low chemosensitivity. Therefore, new therapeutic targets are needed. These could include the downstream pathways of receptor tyrosine kinases, especially the human epidermal growth factor receptor 2 (HER2). Our main objective was to characterize the HER2 status using immunohistochemistry (IHC) and FISH on 118 OCCCs, also considering the novel paradigm of HER2-zero and HER2-low status. Other aims included determination of the association between HER2 status and survival, HER2 gene DNA and RNA NGS analysis, HER2 gene expression analysis, and correlation between IHC and gene expression in HER2-zero and HER2-low cases. Cases with HER2 overexpression/amplification accounted for 5.1% (6/118), with additional 3% harbouring HER2 gene mutation. The remaining 112 (94.9%) cases were HER2-negative. Of these, 75% were classified as HER2-zero and 25% as HER2-low. This percentage of HER2 aberrations is significant concerning their possible therapeutic influence. Cases from the HER2-zero group showed significantly better survival. Although this relationship lost statistical significance in multivariate analysis, the results have potential therapeutic significance. HER2 gene expression analysis showed a significant correlation with HER2 IHC status in the entire cohort (HER2-positive vs. HER2-negative), while in the cohort of only HER2-negative cases, the results did not reach statistical significance, suggesting that gene expression analysis would not be suitable to confirm the subdivision into HER2-low and HER2-zero. Our results also emphasize the need for standardized HER2 testing in OCCC to determine the best predictor of clinical response.

• Klíčová slova
• Gynecopathology, HER2, Immunohistochemistry, Ovarian cancer, Ovarian clear cell carcinoma,
• MeSH
• amplifikace genu MeSH
• epiteliální ovariální karcinom genetika   MeSH
• hybridizace in situ fluorescenční MeSH
• imunohistochemie MeSH
• lidé MeSH
• nádory prsu * genetika   MeSH
• nádory vaječníků * patologie   MeSH
• receptor erbB-2 metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• receptor erbB-2 MeSH

UNLABELLED: Molecular mechanisms of lapatinib resistance in breast cancer are not well understood. The aim of this study was to correlate expression of selected proteins involved in ErbB family signaling pathways with clinical efficacy of lapatinib. Study group included 270 HER2-positive advanced breast cancer patients treated with lapatinib and capecitabine. Immunohistochemical expression of phosphorylated adenosine monophosphate-activated protein (p-AMPK), mitogen-activated protein kinase (p-MAPK), phospho (p)-p70S6K, cyclin E, phosphatase and tensin homolog were analyzed in primary breast cancer samples. The best discriminative value for progression-free survival (PFS) was established for each biomarker and subjected to multivariate analysis. At least one biomarker was determined in 199 patients. Expression of p-p70S6K was independently associated with longer (HR 0.45; 95% CI: 0.25-0.81; p = 0.009), and cyclin E with shorter PFS (HR 1.83; 95% CI: 1.06-3.14; p = 0.029). Expression of p-MAPK (HR 1.61; 95% CI 1.13-2.29; p = 0.009) and cyclin E (HR 2.99; 95% CI: 1.29-6.94; p = 0.011) was correlated with shorter, and expression of estrogen receptor (HR 0.65; 95% CI 0.43-0.98; p = 0.041) with longer overall survival. Expression of p-AMPK negatively impacted response to treatment (HR 3.31; 95% CI 1.48-7.44; p = 0.004) and disease control (HR 3.07; 95% CI 1.25-7.58; p = 0.015). IN CONCLUSION: the efficacy of lapatinib seems to be associated with the activity of downstream signaling pathways - AMPK/mTOR and Ras/Raf/MAPK. Further research is warranted to assess the clinical utility of these data and to determine a potential role of combining lapatinib with MAPK pathway inhibitors.

• Klíčová slova
• breast cancer, epidermal growth factor receptor type 2, lapatinib, mTOR, p-MAPK,
• MeSH
• chinazoliny terapeutické užití   MeSH
• cyklin E metabolismus   MeSH
• dospělí MeSH
• fosforylace účinky léků   MeSH
• hodnocení výsledků zdravotní péče metody   statistika a číselné údaje   MeSH
• imunohistochemie metody   MeSH
• inhibitory proteinkinas farmakologie   MeSH
• Kaplanův-Meierův odhad MeSH
• kinasy ribozomálního proteinu S6, 70-kDa metabolismus   MeSH
• lapatinib MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitogenem aktivované proteinkinasy metabolismus   MeSH
• mladý dospělý MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• prediktivní hodnota testů MeSH
• prognóza MeSH
• proporcionální rizikové modely MeSH
• receptor erbB-2 antagonisté a inhibitory   metabolismus   MeSH
• receptory pro estrogeny metabolismus   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chinazoliny MeSH
• cyklin E MeSH
• inhibitory proteinkinas MeSH
• kinasy ribozomálního proteinu S6, 70-kDa MeSH
• lapatinib MeSH
• mitogenem aktivované proteinkinasy MeSH
• receptor erbB-2 MeSH
• receptory pro estrogeny MeSH

One type of anticancer vaccine relies on the administration of DNA constructs encoding one or multiple tumor-associated antigens (TAAs). The ultimate objective of these preparations, which can be naked or vectored by non-pathogenic viruses, bacteria or yeast cells, is to drive the synthesis of TAAs in the context of an immunostimulatory milieu, resulting in the (re-)elicitation of a tumor-targeting immune response. In spite of encouraging preclinical results, the clinical efficacy of DNA-based vaccines employed as standalone immunotherapeutic interventions in cancer patients appears to be limited. Thus, efforts are currently being devoted to the development of combinatorial regimens that allow DNA-based anticancer vaccines to elicit clinically relevant immune responses. Here, we discuss recent advances in the preclinical and clinical development of this therapeutic paradigm.

• Klíčová slova
• AFP, α-fetoprotein, APC, antigen-presenting cell, CDR, complementarity-determining region, CEA, carcinoembryonic antigen, CIN, cervical intraepithelial neoplasia, CTLA4, cytotoxic T lymphocyte protein 4, DAMP, damage-associated molecular pattern, DC, dendritic cell, FDA, Food and Drug Administration, GM-CSF, granulocyte macrophage colony-stimulating factor, GX-188E, HCC, hepatocellular carcinoma, HNSCC, head and neck squamous cell carcinoma, HPV, human papillomavirus, IL, interleukin, OS, overall survival, OVA, ovalbumin, PAP, prostate acid phosphatase, SCGB2A2, secretoglobin, family 2A, member 2, SOX2, SRY (sex determining region Y)-box 2, T, brachyury homolog, TAA, tumor-associated antigen, TLR, Toll-like receptor, TRA, tumor rejection antigen, Treg, regulatory T cell, VGX-3100, WT1, Wilms tumor 1, adjuvants, dendritic cell, electroporation, mucosal immunity,
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

• MeSH
• dospělí MeSH
• imunohistochemie MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory prsu chemie   farmakoterapie   mortalita   patologie   MeSH
• neoadjuvantní terapie MeSH
• protokoly antitumorózní kombinované chemoterapie terapeutické užití   MeSH
• receptor erbB-2 analýza   MeSH
• receptory pro estrogeny analýza   MeSH
• receptory progesteronu analýza   MeSH
• retrospektivní studie MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• ERBB2 protein, human MeSH Prohlížeč
• receptor erbB-2 MeSH
• receptory pro estrogeny MeSH
• receptory progesteronu MeSH