[Effect of Erlotinib in 2nd and 3rd Line Anticancer Treatment in Patients with Squamous Cell Lung Cancer - Case Series]. / Efekt erlotinibu u pacientu se spinocelulárním karcinomem plic ve 2. a 3. linii protinádorové lécby - kazuistická sdelení.

BACKGROUND: Squamous cell carcinoma of the lung (SCC) represents cca 30-40% of new cases of non-small cell lung cancer (NSCLC) in the Czech Republic. The tyrosine kinase inhibitor erlotinib is indicated as a 1st line treatment for patients with locally advanced and metastatic disease and activating mutations in endothelial growth factor receptor (EGFR), or as a 2nd or 3rd line treatment in EGFR-negative NSCLC patients after chemotherapeutic failure. OBSERVATION: We present three case reports of patients with SCC treated with erlotinib as a 2nd or 3rd line of treatment. All patients were verified by histological analysis of tumor samples. EGFR mutation status was negative in one patient, while the other samples were not suitable for genetic screening. RESULTS: The therapeutic response to erlotinib lasted for 68, 40, and 13 months, resp. The patient with the longest therapeutic response (patient no. 1) is still continuing erlotinib treatment (as of December 2016). The overall survival of the two patients who died was 50 and 43 months, resp. One patient died of an unknown cause with no signs of progression of the disease on CT scans. The other patient died of terminal progression of the oncological disease. All three patients experienced major therapeutic benefit from erlotinib treatment as shown by the long periods of progression-free survival and prolonged overall survival. CONCLUSION: The three case reports demonstrate that erlotinib may be effective as a 2nd or 3rd line treatment in patients with SCC, especially in patients with limited alternative anticancer treatment options.Key words: non-small cell lung cancer - squamous cell carcinoma - erlotinib - treatment - tyrosine kinase inhibitor The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 5. 8. 2016Accepted: 14. 12. 2016.

[Extraoseus Ewings Sarcoma, Primary Affection of Uterine Cervix--Case Report]. / Extraoseální Ewinguv sarkom, primární postizení delozního cípku--kazuistika.

BACKGROUND: Ewing's sarcoma is usually diagnosed in adolescents and young adults, peak of incidence is around 15 years of age. Primary localization is mostly in the skeleton of long bones and chest wall. Primary extraosseous involvement rarely occurs, incidence increases with age. CASE: We present a case report of a 57-year-old patient with locally advanced tumors of the cervix, clinical stage IIB. Due to histological and molecular genetic examination revealing EWS -ERG fusion gene, Ewing's sarcoma was diagnosed. CT revealed pathological pelvic lymphadenopathy and multiple pulmonary bilateral methastases, scintigraphy did not prove any affection of skeleton. The patient underwent a two-stage intensive chemotherapy regimens VIDE (vincristine, ifosfamide, doxorubicin, etoposide) and VAI (vincristine, actinomycin D, ifosfamide). During the second phase, concomitant radiotherapy of pelvis was aplied. According to PET/CT, complete remission was achieved. Whole-lung irradiation was applied in consolidation of the result. CONCLUSION: Primary Ewing's sarcoma of the cervix is an extremely rare disease. To our knowledge, only 12 cases was presented until this time. The average age at time of dia-gnosis was 35 years. Unlike the previous reports, we initially diagnosed distant metastases. The treatment was led according to the protocol Ewing 2008 designed for primary skeletal Ewing's sarcoma. Currently, 18 months after the therapy, the patient is without signs of disease. However, long-term follow-up is necessary.

[Molecular biological diagnostics of KRAS and BRAF mutations in patients with colorectal cancer - laboratory experience]. / Molekulárne biologická diagnostika mutací genu KRAS a BRAF u pacientu s kolorektálním karcinomem - zkusenosti laboratorního pracoviste

BACKGROUND: Targeted biological therapy based on blocking growth factor receptors and inhibition of cancer-inducing signaling pathways is a new treatment facility for patients with colorectal cancer (CRC). Therapeutic agents are monoclonal antibodies targeting epidermal growth factor receptor (EGFR). Gene aberrations in the EGFR-induced pathways are negative predictors of therapeutic response. Determination of -non-mutated KRAS is a requirement for the indication of targeted anti-EGFR therapy in the present time, BRAF mutation analysis is recommended. Comparison of our results with published data and verification of routine laboratory methods in relation to diagnostic kits were the purposes of this study. PATIENTS AND METHODS: In addition to routine methods based on PCR, direct sequencing as well as two diagnostic kits for KRAS (codon 12 and 13) and BRAF (codon 600) mutation analysis were used for 132 patients. RESULTS: KRAS mutations were detected in 45 patients (34%), V600E mutation of the BRAF gene in 9 patients (7%). Both mutations simultaneously were not detected. Tissues from primary tumor and metastases were available from 33 patients. KRAS mutation was detected in 13 cases of this group. KRAS mutations in tumor and metastasis were of the same type in 9 patients; types of mutation in both tissues were different in one case. KRAS mutation only in one tissue was detected in 3 cases. BRAF mutation in both tissues was detected in the 4 patients. A low percentage of tumor cells in 17 patients specimen did not allow performance of routine analysis and diagnostic kit was used. CONCLUSION: The frequency of KRAS and BRAF mutations in our cohort of patients corresponds to published data. The suitability of metastatic tissue analysis due to tumor heterogeneity was confirmed. KRAS analysis requires a comprehensive methodological approach with regard to reduced DNA quality and different percentage of tumor cells in tissue. For this reason, commercial diagnostic kits constitute a suitable supplement to standard methods.

[Malignant melanoma treated with radical chemotherapy, resemblance histology of melanoma to soft tissue sarcomas, case report]. / Maligní melanom lécený intenzivní chemoterapií, podobnost histologického obrazu maligního melanomu a nádoru mekkých tkání, kazuistika pacientky.

BACKGROUND: Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. CASE: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. CONCLUSION: The case demonstrates the limits of the sensitivity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma.

Herpesvirus-associated papillomatosis in a green lizard.

Papillomatous skin lesions from a green lizard (Lacerta viridis) were examined histologically, using electron microscopy and DNA was isolated from the lesions for herpes-viral DNA detection. Histology confirmed the lesions to be squamous epithelial papillomas. Using electron microscopy, no virus particles were detected. The specific sequence of herpesviral DNA-directed DNA polymerase (EC 2.7.7.7) was amplified using degenerate primers in a nested format. The 235-base-pair (bp) sequence was sequenced and compared with previously published DNA-directed DNA polymerase sequences from various reptile herpesviruses. The sequence from the green lizard showed significant similarity with sequence of fibropapilloma-associated turtle herpesviruses from sea turtles.