A semi-automated microscopic image analysis method for scoring Ki-67 nuclear immunostaining

Author(s):Show less -

S.M. Fernezlian ^[1] ; C.M. Baldavira ^[2] ; M.L.F. de Souza ^[3] ; C. Farhat ^[4] ; A.F. de Vilhena ^[5] ; J.C.N. Pereira ; J.R.M. de Campos ; T. Takagaki ^[8] ; M.L. Balancin ^[9] ; A.M. Ab'Saber ^[10] ; V.L. Capelozzi ^[11]

Affiliation:Show less -

^[1] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[2] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[3] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[4] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[5] Instituto do Coração. Departamento de Cirurgia Torácica - Brasil

^[8] Universidade de São Paulo. Instituto do Coração, Faculdade de Medicina. Divisão de Pneumologia - Brasil

^[9] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[10] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

^[11] Universidade de São Paulo. Departamento de Patologia, Faculdade de Medicina. Laboratório de Genômica e Histomorfometria - Brasil

• Document type: Journal article
• Source: Brazilian Journal of Medical and Biological Research; v. 56, 2023-11-13.

Abstract

Nuclear proliferation marker MIB-1 (Ki-67) immunohistochemistry (IHC) is used to examine tumor cell proliferation. However, the diagnostic or prognostic value of the Ki-67 nuclear staining intensity and location, defined as nuclear gradient (NG), has not been assessed. This study examined the potential association between Ki-67 NG and cell cycle phases and its effect on the prognosis of pulmonary typical carcinoid (PTC) tumors. We propose a method for classifying the NG of Ki-67 during the cell cycle and compare the results between PTC, pulmonary adenocarcinoma (PAD), and breast ductal carcinoma (BDC). A literature review and objective analysis of IHC-stained paraffin sections were used to determine the Ki-67 labeling index and composed a stratification of the NG into NG1, NG2, and NG3/4 categories. A semi-automated image analysis protocol was established to determine the Ki-67 NG in PTC, PAD, and BDC. High intraobserver consistency and moderate interobserver agreement were achieved in the determination of Ki-67 NG in tumor specimens. NG1 and NG2 were lower in PTC than in PAD and BDC. Cox multivariate analysis of PTC after adjusting for age and number of metastatic lymph nodes showed that Ki-67 NG1 and NG2 significantly predicted clinical outcomes. The semi-automated method for quantification of Ki-67 nuclear immunostaining proposed in this study could become a valuable diagnostic and prognostic tool in PTC. (AU)

• FAPESP's process: 23/02755-0 - Evaluation of epithelial-mesenchymal transition protein expression as a new perspective in biomarkers for determining prognosis, response and resistance to targeted therapy in non-small cell lung carcinomas
• Grantee: Camila Machado Baldavira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 18/20403-6 - Biomolecular markers of proliferation and remodeling in acute and chronic respiratory diseases: promising therapeutic targets
• Grantee: Vera Luiza Capelozzi
• Support Opportunities: Research Projects - Thematic Grants