Usefulness of complementary next-generation sequencing and quantitative immunohistochemistry panels for predicting brain metastases and selecting treatment outcomes of non-small cell lung cancer

Autor(es):Mostrar menos -

Machado-Rugolo, Juliana ^[1] ; Fabro, Alexandre Todorovic ^[2] ; Ascheri, Daniel ^[3] ; Farhat, Cecilia ^[3] ; Ab'Saber, Alexandre Muxfeldt ^[3] ; de Sa, Vanessa Karen ^[3] ; Nagai, Maria Aparecida ^[4] ; Takagaki, Teresa ^[5] ; Terra, Ricardo ^{[6, 7]} ; Parra, Edwin Roger ^[8] ; Capelozzi, Vera Luiza ^[3]

Afiliação do(s) autor(es)

^[1] State Univ Soo Paulo, Fac Med, Clin Hosp, BR-18618682 Botucatu, SP - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Sch Med, Dept Pathol & Legal Med, BR-14049900 Ribeirao Preto - Brazil

^[3] Univ Sao Paulo, Med Sch, Dept Pathol, Lab Genom & Histomorphometry, BR-01246903 Sao Paulo - Brazil

^[4] Clin Hosp, Dept Oncol, BR-01246903 Sao Paulo - Brazil

^[5] Univ Sao Paulo, Fac Med, Heart Inst Incor, Div Pneumol, BR-01246903 Sao Paulo - Brazil

^[6] Inst Canc Sao Paulo, Dept Thorac Surg, BR-01246903 Sao Paulo - Brazil

^[7] Heart Inst Incor, Dept Thorac Surg, BR-01246903 Sao Paulo - Brazil

^[8] Univ Texas MD Anderson Canc Ctr, Dept Translat Mol Pathol, Houston, TX 77030 - USA

• Tipo de documento: Artigo Científico
• Fonte: HUMAN PATHOLOGY; v. 83, p. 177-191, JAN 2019.
• Citações Web of Science: 0

Resumo

To demonstrate the usefulness of complementary next-generation sequencing (NGS) and immunohistochemistry (IHC) counting, we analyzed 196 patients with non-small cell lung cancer who underwent surgical resection and adjuvant chemotherapy. Formalin-fixed, paraffin-embedded samples of adenocarcinoma (ADC), squamous cell carcinoma, and large cell carcinoma were used to prepare tissue microarrays and were examined by protein H-score IHC image analysis and NGS for oncogenes and proto-oncogenes and genes of tumor suppressors, immune checkpoints, epithelial-mesenchymal transition factors, tyrosine kinase receptors, and vascular endothelial growth factors. In patients with brain metastases, primary tumors expressed lower PIK3CA protein levels. Overexpression of p53 and a higher PD-LI protein H-score were detected in patients who underwent surgical treatment followed by chemotherapy as compared with those who underwent only surgical treatment The absence of brain metastases was associated with wild-type sequences of genes EGFR, CD267, CTLA-4, and ZEBI. The combination of protein overexpression according to IHC and mutation according to NGS was rare (ie, represented by a very low percentage of concordant cases), except for p53 and vascular endothelial growth factor. Our data suggest that protein levels detected by IHC may be a useful complementary tool when mutations are not detected by NGS and also support the idea to expand this approach beyond ADC to include squamous cell carcinoma and even large cell carcinoma, particularly for patients with unusual clinical characteristics. Conversely, well-pronounced immunogenotypic features seemed to predict the clinical outcome after univariate and multivariate analyses. Patients with a solid ADC subtype and mutated genes EGFR, CTLA4, PDCDILG2, or ZEBI complemented with PD-L1 or p53 protein lower expression that only underwent surgical treatment who develop brain metastases may have the worst prognosis. (C) 2018 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 13/14277-4 - Prognóstico e evolução clínica de novos e vigentes biomarcadores genéticos e protéicos em câncer de pulmão
• Beneficiário: Vera Luiza Capelozzi
• Modalidade de apoio: Auxílio à Pesquisa - Regular