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CC BY 4.0 · Rev Bras Ginecol Obstet 2018; 40(12): 779-786
DOI: 10.1055/s-0038-1673700
Original Article
Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil

Identification of a Subtype of Poorly Differentiated Invasive Ductal Carcinoma of the Breast Based on Vimentin and E-cadherin Expression

Identificação de um subtipo pouco diferenciado de carcinoma ductal invasivo de mama, baseado na expressão da vimentina e E-caderina
Leonardo Fleury Orlandini
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Francisco José Cândido dos Reis
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Willian Abraham da Silveira
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Marcelo Guimarães Tiezzi
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Jurandyr Moreira de Andrade
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Alfredo Ribeiro-Silva
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
,
Ryan Deaton
2   University of Illinois at Chicago, Chicago, IL, United States
,
Maarten Bosland
2   University of Illinois at Chicago, Chicago, IL, United States
,
Daniel Guimarães Tiezzi
1   Breast Disease Division, Department of Gynecology and Obstetrics, School of Medicine, Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto, SP, Brazil
› Author Affiliations
Further Information

Publication History

19 April 2018

09 August 2018

Publication Date:
25 October 2018 (online)

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Abstract

Objective The use of molecular markers can identify a subgroup of tumors with distinct recurrence patterns. The present study aimed to characterize the immunohistochemical expression of vimentin (VIM), of E-cadherin (CDH1), and of cytokeratin 5 (CK5) in patients with invasive ductal carcinomas (IDCs).

Methods We have constructed a tissue microarray (TMA) from 87 patients with IDC of the breast. Immunohistochemistry (IHC) was performed to study the expression of estrogen and progesterone receptors (ER and PgR), human epidermal growth factor receptor 2 (HER2), VIM, CDH1, CK5, and Ki67. The tumors were classified as luminal A and B (n = 39), HER2 enriched (n = 25), and triple-negative (TNBC) (n = 23), based on the IHC expression.

Results We have observed that luminal A and B tumors lack the VIM+/CDH1-/low phenotype. This phenotype was observed in 16.5% of the HER2+ tumors and in 60% of the TNBC tumors (p = 0.0001). Out of a total of 20 TNBC tumors, the CK5 (basal-like marker) was positive in 11 of them. The VIM+/CDH1-/low phenotype was observed in 5 CK5+ TNBC tumors (45%) and in 7 out of 9 CK5- TNBC tumors (78%) (p = 0.02). The median Ki67 index in the VIM+/CDH1-/low tumors was 13.6 (range: 17.8–45.4) compared with 9.8 (range: 4.1–38.1) in other tumors (p = 0.0007). The presence of lymph node metastasis was less frequent in patients with VIM+/CDH1-/low tumors (23% versus 61%; X2 test; p = 0.01).

Conclusion Our findings suggest that the expression of VIM and CDH1 can identify a subset of IDCs of the breast with a mesenchymal phenotype associated with poor prognosis, high-grade lesion, and high mitotic index.

Resumo

Objetivo O uso de marcadores moleculares pode identificar subtipos tumorais com diferentes taxas de recidiva. O objetivo do presente estudo é caracterizar a expressão imunohistoquímica da vimentina (VIM), da E-caderina (CDH1) e de CK5 em pacientes com carcinoma ductal invasivo (CDI) da mama.

Métodos Utilizamos uma matriz de amostras teciduais (TMA, na sigla em inglês) de 87 pacientes com CDI da mama. Para avaliar a expressão dos receptores de estrogênio (RE) e receptores de progesterona (RP), HER2, VIM, CDH1, CK5 e Ki67, utilizamos imunohistoquímica. Os tumores foram classificados como luminal A e B (n = 39), HER2+ (n = 25) e triplo negativo (TNBC) (n = 23).

Resultados Foi observado que tumores luminais A e B não expressaram o fenótipo VIM+/CDH1-/low. Este fenótipo foi observado em 16,5% dos tumores HER2+ e em 60% dos tumores TNBC (p = 0,0001). Dos 20 tumores TNBC, a CK5 (marcador de tumor basalóide) foi super expressa em 11 amostras. O fenótipo VIM+/CDH1-/low foi observado em 5 tumores CK5+ TNBC (45%) e em 7 dos 9 tumores CK5- TNBC (78%) (p = 0,02). A expressão média de Ki67 nos tumores VIM+/CDH1-/low foi 13.6 (amplitude de 17,8 a 45,4) comparado com 9,8 (amplitude de 4,1 a 38,1) nos outros tumores (p = 0,0007). A presença de metástase linfonodal foi menor em tumores com fenótipo VIM+/CDH1-/low (23% contra 61%; teste X2 ; p = 0,01).

Conclusão Nossos achados sugerem que a expressão de VIM e CDH1 pode identificar um subtipo de CDI da mama com fenótipo mesenquimal associado a pior prognóstico, lesões de alto grau e alto índice mitótico.

Keywords

breast cancer - epithelial-mesenchymal transition - vimentin - e-cadherin - prognostic factors

Palavras-chave

câncer de mama - transição epitelial-mesenquimal - vimentina - e-caderina - fatores prognósticos

Contributions

Tiezzi D. G. participated in the design of the study, in the elaboration of the draft of the manuscript and performed the statistical analysis. Andrade J. M. and Reis F.J.C. participated in the design and in the coordination of the study and helped to elaborate the draft of the manuscript. Tiezzi M.G. performed the immunohistochemical analysis. Bosland M. and Deaton R. were responsible for the digital analysis. Orlandini L. F. contributed in the elaboration of the draft of the manuscript. Silveira W. A. contributed with the data collection and with the selection of the paraffin blocks.


 

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