O número mínimo de células neoplásicas actualmente recomendado para avaliar a amplificação do gene HER2 em cancro da mama não é suficiente

Recentemente foi publicado no Histopathology um trabalho desenvolvido pelo Laboratório de Anatomia Patológica do Ipatimup Diagnósticos em colaboração com os serviços de Anatomia Patológica do Hospital Pedro Hispano e do Hospital Prof. Doutor Fernando Fonseca sobre o número mínimo de células neoplásicas necessárias para quantificar de forma reprodutível a amplificação do gene HER2 em cancro da mama.
O trabalho consistiu na avaliação do estado de amplificação do gene HER2 em carcinoma da mama por 4 observadores diferentes usando números crescentes de células neoplásicas. Os autores concluíram que o número mínimo de células neoplásicas actualmente recomendado nas guidelines internacionais (20 células) não é suficiente e deveria ser aumentado para pelo menos 40 células. Adicionalmente, casos com amplificação duvidosa devem ser sujeitos a segunda avaliação por um observador experiente.

Autores e Afiliações:

António Polónia ^1,2, Catarina Eloy ^1,2, João Pinto ³, Ana Costa Braga ^4,5, Guilherme Oliveira ¹, Fernando C. Schmitt ^1,2,6
1 Department of Pathology, Ipatimup Diagnostics, Ipatimup, University of Porto, Porto, Portugal
² FMUP, Faculty of Medicine, University of Porto, Porto, Portugal
³ Department of Pathology, Hospital Pedro Hispano, ULS Matosinhos, Matosinhos, Portugal
⁴ Department of Pathology, Hospital Prof. Doutor Fernando Fonseca, EPE, Amadora, Portugal
⁵ NOVA MEDICAL SCHOOL - Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisboa, Portugal
⁶ Laboratoire National de Santé, Dudelange,Luxembourg

Abstract:

AIM: To evaluate the intraobserver and interobserver reproducibility of the HER2 in-situ hybridization (ISH) test in breast cancer by measuring the impact of counting different numbers of invasive cancer cells.
METHODS AND RESULTS: A cohort of 101 primary invasive breast cancer cases were evaluated for HER2 gene amplification by silver ISH, and the concordance among four observers with different levels of experience, counting different numbers of invasive cancer cells, was determined. The evaluation of the samples included scoring 20 nuclei, in three different areas. The cases were scored twice, with a washout interval of at least 2 weeks. We observed an increase in the intraobserver concordance rate between the first and second evaluations with an increase in cell count. A count of 60 invasive cells was needed to obtain a concordance rate near 95% and an agreement rate greater than 0.80 by all observers. The interobserver concordance rate of the HER2 test also increased with the increase in cell count, reaching at least a 90% concordance rate with a count of 60 invasive cells. The median variability of both the HER2/CEP17 ratio and the average HER2 copy number between different evaluations decreased with the increase in cell count, being statistically higher in HER2-positive cases.
CONCLUSIONS: The minimal cell number recommended in current guidelines should be raised to at least 40, and preferably 60, invasive cells. Moreover, cases with amplification levels close to the threshold should be subjected to a dual count from an experienced observer.

Revista: Histopathology

Link: http://onlinelibrary.wiley.com/doi/10.1111/his.13208/abstract