StreszczenieW Polsce rak płuca jest najczęstszą przyczyną zgonów spowodowanych chorobą nowotworową wśród mężczyzn, a od 2009 r. także wśród kobiet. W niedrobnokomórkowym raku płuca (NDRP) może dojść do nieprawidłowości w metabolizmie genu EGFR, takich jak silna ekspresja białka EGFR, amplifikacje lub mutacje somatyczne w domenie kinazy tyrozynowej (TK). Leczenie chorych z mutacją aktywującą w genie EGFR inhibitorami TK EGFR jest skuteczniejsze niż standardowa chemioterapia, ale kluczem do sukcesu jest prawidłowa kwalifikacja pacjenta, realizowana dzięki współpracy interdyscyplinarnego zespołu torakochirurgów, patomorfologów, genetyków -biologów molekularnych i onkologów. Kwalifikacja pacjentów do badania obejmowała ocenę kliniczną oraz patomorfologiczną. Badanie genetyczne wykonano przy użyciu metody real-time PCR. Do analizy najczęstszych 29 mutacji w genie EGFR i 7 najczęstszych mutacji w genie KRAS użyto odpowiednio sond hydrolizujących i hybrydyzujących. U dziesięciu z 77 pacjentów wykryto mutację aktywującą, w przeważającej większości w eksonach 19 i 21, co stanowi Ocena częstości występowania mutacji w genie EGFR i współwystępowania mutacji EGFR i KRAS metodą reakcji łańcuchowej polimerazy w czasie rzeczywistym u chorych na raka gruczołowego płuca -czy kliniczno--patologiczny model kwalifikacji pacjenta do leczenia celowanego może mieć wpływ na czas uzyskania wyniku genetycznego?Analysis of EGFR mutation frequency and coexistence of KRAS and EGFR mutations using RT-PCR in lung adenocarcinoma: may a clinical and pathological model of a patient's qualification for targeted therapy have an impact on time to obtain genetic results? AbstractIn Poland, lung cancer is the most common cause of cancer deaths among men, and since 2009 in women as well. Nonsmall cell lung carcinoma (NSCLC) can lead to abnormalities in the metabolism of EGFR, such as strong EGFR protein expression, amplification or presence of somatic mutations in the tyrosine kinase domain (TK). Targeted therapy (EGFR TK inhibitors) for patients diagnosed with activating EGFR mutations is more effective than standard chemotherapy, but the key to success is proper classification of the patient, carried out through the cooperation of an interdisciplinary team: thoracic surgeons, pathologists, geneticists/molecular biologists and oncologists. Eligibility for the study included clinical and pathological assessment. Genetic testing was performed using real-time PCR: we analysed 29 most common EGFR mutations (Entrogen) and 9 most common KRAS mutations (TibMolBiol).

Background: The prediction of tumor malignancy is still one of the most demanding diagnostic tasks in urinary bladder cancer because of its clinicopathological heterogeneity. The aim of this study was to evaluate the expression of PD-L1 in tumor cells (TCs) and immune effector cells (IECs) as well as the pattern of distribution of PD-L1+ IECs within the tumor (dispersed or aggregated) and their association with survival of patients with pT1-pT4 urinary bladder cancer. Materials and methods: 110 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent radical cystectomy/cystoprostatectomy between 2011 and 2014 were included in the study. Paraffin blocks most representative of the tumor were selected for H&E staining as well as immunostaining with the use of rabbit anti-PD-L1 (Ventana clone SP142, Roche). In each sample, the area of the tumor containing PD-L1+ IECs, as well as, the pattern of distribution (dispersed or aggregated) of PD-L1+ immune effector cells within the tumor were analyzed. In addition, the expression of PD-L1 in TCs was also assessed. Results: Patients had a shorter survival time in pT2-pT4 cases without TCs expressing PD-L1 (p = 0.007) and/or when PD-L1+ IECs displayed a predominantly dispersed pattern of distribution (p = 0.013). Conclusions: The expression of PD-L1 on TCs and IECs is a prognostic factor which allows for stratification of patient survival in UBC. The predominance of dispersed or aggregated pattern of distribution of PD-L1+ IECs in the tumor may be considered as a new prognostic factor in pT1-T4 UBC and indicate the functional status of the immune system.

Background: Morbidity and mortality relating to urinary bladder cancer have remained largely unchanged for many years. Similarly, the five-year survival rate in this disease has not improved considerably. New developments in individualized therapy necessitate the search for novel factors that could predict the development of malignancy in UBC. In this study, we provide the first evidence that the expression of ROR alpha transcription factor influences the development of malignancy in UBC. Materials and methods: 105 patients with stage pT1-pT4 urothelial bladder carcinoma who underwent cystectomy were included in the study. 4 µm tissue samples were stained immunohistochemically with a polyclonal anti-RORa antibody. The expression of RORa by the tumor cells (TCs) was assessed by counting TCs with a cytoplasmic and/or nuclear staining for RORa per 1000 TCs. The association between the extent of RORa expression and non-classic differentiation, tumor advancement (pT), grade (G) and regional lymph node spread was analyzed. Results: The cytoplasmic expression of RORa was detected in near all analyzed tumor samples (104/105). The extent of RORa expression was significantly higher in tumors which were more malignant with more propensity for non-classic differentiation and lymph node metastasis. We noted a lower percentage of TCs expressing RORa in poorly differentiated tumors (G3), compared to tumors moderately and higher differentiated (G1/G2). Conclusions: Our results suggest that RORa may play a significant role in the progression of urinary bladder cancer. RORa has a broad spectrum of regulatory activity relating to cell and tissue differentiation the mechanism of which is not fully understood. This study represents another step in the process of understanding the mechanisms of RORa regulation and highlights its potential role as a therapeutic target in urothelial bladder cancer.

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