Data documento
02/05/2024

Título
EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil

Autor(es)
Alves Pinto I, - de Oliveira Cavagna R, - Virginio da Silva AL, - Dias JM, - Santana IV, - Souza LC, - Ferreira da Silva FA, - Biazotto Fernandes MF, - Junqueira Pinto GD, - Negreiros IS, - Santiago Gonçalves MF, - de Paula FE, - Berardinelli GN, - Casagrande GMS, - Oliveira da Silva M, - Albino da Silva EC, - de Oliveira MA, - Jacinto AA, - Duval da Silva V, - Reis RM, - De Marchi P, - Leal LF.

Resumo
Background: Targeted and immunotherapies are currently moving toward early-stage settings for patients with non-small cell lung cancer (NSCLC). Predictive biomarkers data are scarce in this scenario. We aimed to describe the frequency of EGFR mutations and PD-L1 expression levels in early-stage non-squamous patients with NSCLC from a large, single Brazilian oncology center. Methods: We retrospectively evaluated patients with NSCLC diagnosed at an early-stage (IB to IIIA-AJCC seventh edition) at Barretos Cancer Hospital (n = 302). EGFR mutational status was assessed in FFPE tumor tissues using distinct methodologies (NGS, Cobas, or Sanger sequencing). PD-L1 expression was evaluated by immunohistochemistry (clone 22C3) and reported as Tumor Proportion Score (TPS), categorized as <1%, 1-49%, and ≥50%. We evaluated the association between EGFR mutational status and PD-L1 expression with sociodemographic and clinicopathological parameters by Fisher’s test, qui-square test, and logistic regression. Survival analysis was assessed by the Kaplan-Meier method and Cox regression model. Results: EGFR mutations were detected in 17.3% (n = 48) of cases and were associated with female sex, never smokers, and longer overall and event-free survival. PD-L1 positivity was observed in 36.7% (n = 69) of cases [TPS 1-49% n = 44(23.4%); TPS ≥50% n = 25(13.3%)]. PD-L1 positivity was associated with smoking, weight loss, and higher disease stages (IIB/IIIA). Conclusion: The frequencies of EGFR mutations and PD-L1 positivity were described for early-stage non-squamous patients with NSCLC. These results will be essential for guiding treatment strategies with the recent approvals of osimertinib and immunotherapy in the adjuvant setting.

Citação
Alves Pinto I, de Oliveira Cavagna R, Virginio da Silva AL, Dias JM, Santana IV, Souza LC, Ferreira da Silva FA, Biazotto Fernandes MF, Junqueira Pinto GD, Negreiros IS, Santiago Gonçalves MF, de Paula FE, Berardinelli GN, Casagrande GMS, Oliveira da Silva M, Albino da Silva EC, de Oliveira MA, Jacinto AA, Duval da Silva V, Reis RM, De Marchi P, Leal LF. EGFR Mutations and PD-L1 Expression in Early-Stage Non-Small Cell Lung Cancer: A Real-World Data From a Single Center in Brazil. Oncologist. 2022 Nov 3;27(11):e899-e907. doi: 10.1093/oncolo/oyac167. PMID: 36099421; PMCID: PMC9632322.

Data documento
02/05/2024

Título
High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population

Autor(es)
Moreno DA - Bonatelli M - Antoniazzi AP - de Paula FE - Leal LF - Garcia FAO - de Paula AE - Teixeira GR - Santana IVV - Saggioro F - Neder L - Valera ET - Scrideli CA - Stavale J - Malheiros SMF - Lima M - Hajj GNM - Garcia-Rivello H - Christiansen S - Nunes S - Gil-da-Costa MJ - Pinheiro J - Martins FD - Junior CA - Mançano BM - Reis RM.

Resumo
Medulloblastomas are the most common primary malignant brain tumors in children. They are divided into molecular subgroups: WNT-activated, SHH-Activated, TP53 mutant or wild type, and non-WNT/non-SHH (Groups 3 and 4). WNT-activated medulloblastomas are usually caused by mutations in the CTNNB1 gene (85%–90%), and most remaining cases of CTNNB1 wild type are thought to be caused by germline mutations in APC. So far, the frequencies of CTNNB1 have been reported mainly in North American and European populations. The aim of this study was to report the frequency of CTNNB1 mutations in WNT-activated medulloblastomas in a Latin-Iberian population and correlate with their clinicopathological characteristics.

Citação
Moreno DA, Bonatelli M, Antoniazzi AP, de Paula FE, Leal LF, Garcia FAO, de Paula AE, Teixeira GR, Santana IVV, Saggioro F, Neder L, Valera ET, Scrideli CA, Stavale J, Malheiros SMF, Lima M, Hajj GNM, Garcia-Rivello H, Christiansen S, Nunes S, Gil-da-Costa MJ, Pinheiro J, Martins FD, Junior CA, Mançano BM, Reis RM. High frequency of WNT-activated medulloblastomas with CTNNB1 wild type suggests a higher proportion of hereditary cases in a Latin-Iberian population. Front Oncol. 2023 Sep 4;13:1237170. doi: 10.3389/fonc.2023.1237170. PMID: 37746264; PMCID: PMC10513896.

Data documento
03/05/2024

Título
Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs

Autor(es)
Casagrande GMS, - Silva MO, - Reis RM, - Leal LF.

Palavras chave
biomarkers - liquid biopsy - lung cancer - precision medicine

Resumo
Lung cancer is the deadliest cancer worldwide. Tissue biopsy is currently employed for the diagnosis and molecular stratification of lung cancer. Liquid biopsy is a minimally invasive approach to determine biomarkers from body fluids, such as blood, urine, sputum, and saliva. Tumor cells release cfDNA, ctDNA, exosomes, miRNAs, circRNAs, CTCs, and DNA methylated fragments, among others, which can be successfully used as biomarkers for diagnosis, prognosis, and prediction of treatment response. Predictive biomarkers are well-established for managing lung cancer, and liquid biopsy options have emerged in the last few years. Currently, detecting EGFR p.(Tyr790Met) mutation in plasma samples from lung cancer patients has been used for predicting response and monitoring tyrosine kinase inhibitors (TKi)-treated patients with lung cancer. In addition, many efforts continue to bring more sensitive technologies to improve the detection of clinically relevant biomarkers for lung cancer. Moreover, liquid biopsy can dramatically decrease the turnaround time for laboratory reports, accelerating the beginning of treatment and improving the overall survival of lung cancer patients. Herein, we summarized all available and emerging approaches of liquid biopsy-techniques, molecules, and sample type-for lung cancer.

Citação
Casagrande GMS, Silva MO, Reis RM, Leal LF. Liquid Biopsy for Lung Cancer: Up-to-Date and Perspectives for Screening Programs. Int J Mol Sci. 2023 Jan 28;24(3):2505. doi: 10.3390/ijms24032505. PMID: 36768828; PMCID: PMC9917347.

Data documento
03/05/2024

Título
Somatic mutation detection and KRAS amplification in testicular germ cell tumors

Autor(es)
Cabral ERM, - Pacanhella MF, - Lengert AVH, - Dos Reis MB, - Leal LF, - de Lima MA, - da Silva ALV, - Pinto IA, - Reis RM, - Pinto MT, - Cárcano FM.

Palavras chave
K-ras Gene - TP53 Gene - mutation - next-generation sequencing - testicular germ cell tumor - testicular neoplasms

Resumo
Background: Testicular Germ Cell Tumors (TGCT) are the most common cancer among young adult men. The TGCT histopathology is diverse, and the frequency of genomic alterations, along with their prognostic role, remains largely unexplored. Herein, we evaluate the mutation profile of a 15-driver gene panel and copy number variation of KRAS in a large series of TGCT from a single reference cancer center. Materials and methods: A cohort of 97 patients with TGCT, diagnosed at the Barretos Cancer Hospital, was evaluated. Real-time PCR was used to assess copy number variation (CNV) of the KRAS gene in 51 cases, and the mutation analysis was performed using the TruSight Tumor 15 (Illumina) panel (TST15) in 65 patients. Univariate analysis was used to compare sample categories in relation to mutational frequencies. Survival analysis was conducted by the Kaplan-Meier method and log-rank test. Results: KRAS copy number gain was a very frequent event (80.4%) in TGCT and presented a worse prognosis compared with the group with no KRAS copy gain (10y-OS, 90% vs. 81.5%, p = 0.048). Among the 65 TGCT cases, different variants were identified in 11 of 15 genes of the panel, and the TP53 gene was the most recurrently mutated driver gene (27.7%). Variants were also detected in genes such as KIT, KRAS, PDGFRA, EGFR, BRAF, RET, NRAS, PIK3CA, MET, and ERBB2, with some of them potentially targetable. Conclusion: Although larger studies incorporating collaborative networks may shed the light on the molecular landscape of TGCT, our findings unveal the potential of actionable variants in clinical management for applying targeted therapies.

Citação
Cabral ERM, Pacanhella MF, Lengert AVH, Dos Reis MB, Leal LF, de Lima MA, da Silva ALV, Pinto IA, Reis RM, Pinto MT, Cárcano FM. Somatic mutation detection and KRAS amplification in testicular germ cell tumors. Front Oncol. 2023 Mar 16;13:1133363. doi: 10.3389/fonc.2023.1133363. PMID: 37007070; PMCID: PMC10060882.

Data documento
02/05/2024

Título
The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high‐grade cervical lesion detection in liquid‐based cytology

Autor(es)
Causin RL, - Sussuchi da Silva L, - Leal LF, - Possati-Resende JC, - Evangelista AF, - Matsushita GM, - Scapulatempo-Neto C, - Tavares Guerreiro Fregnani JH, - Antônio de Oliveira M, - Musselwhite LW, - Chiquitelli Marques MM, - Reis RM.

Palavras chave
biomarkers - cervical cancer - cervical intraepithelial neoplasia - gene expression - liquid‐based cytology

Resumo
Background: Some studies reported that differential gene expression could be used as a biomarker for high‐grade cervical lesion identification. The aim was to evaluate the gene expression profile of cervical intraepithelial neoplasia (CIN) to identify a gene expression signature of CIN2+ in liquid‐based cytology (LBC) samples. Methods: LBC samples (n = 85) obtained from women who underwent colposcopy were included with benign (n = 13), CIN1 (n = 26), CIN2 (n = 16), and CIN3 (n = 30) diagnoses. After RNA isolation, gene expression profiling was performed using the nCounter PanCancer Pathways, which consists of 730 cancer‐related genes. The genes identified were in silico expression evaluated using the UALCAN database. An accurate prediction model to discriminate CIN2+ from

Descrição

Citação
Causin RL, Sussuchi da Silva L, Leal LF, Possati-Resende JC, Evangelista AF, Matsushita GM, Scapulatempo-Neto C, Tavares Guerreiro Fregnani JH, Antônio de Oliveira M, Musselwhite LW, Chiquitelli Marques MM, Reis RM. The digital expression profile of BMP7, CDKN2C, HIST1H3G, and PKMYT1 genes improves high-grade cervical lesion detection in liquid-based cytology. Cancer Cytopathol. 2023 Jul;131(7):454-464. doi: 10.1002/cncy.22704. Epub 2023 Apr 17. PMID: 37069588.