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Clin Breast Cancer. 2018 Oct;18(5):e1111-e1116. doi: 10.1016/j.clbc.2018.06.005. Epub 2018 Jun 18.

Claudin-4 Expression Is Associated With Disease-Free Survival in Breast Carcinoma-in-Situ: Mean Follow-up of 8.2 Years.

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Woman's Hospital Prof Dr José Aristodemo Pinotti, CAISM, UNICAMP (State University of Campinas), Campinas, Brazil. Electronic address:
Woman's Hospital Prof Dr José Aristodemo Pinotti, CAISM, UNICAMP (State University of Campinas), Campinas, Brazil.
AC Camargo Cancer Center, R. Prof Antônio Prudente, Liberdade, Brazil.



Claudins are tight junctions associated with breast cancer prognosis. The claudin-low intrinsic subtype of invasive carcinoma is associated with high-grade carcinoma, low junction molecule expression, and worse response to chemotherapy. However, it is not known whether the expression of claudins may provide clues as to carcinoma-in-situ (CIS) prognosis. The aim of this study was evaluate claudin-4 expression in CIS and its association with disease-free survival and histologic type of local recurrence (in situ or invasive).


A tissue microarray block, constructed from 137 pure CIS paraffin blocks, was submitted to immunohistochemical staining for claudin-4, β-catenin, E-cadherin, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, and Ki-67. A claudin-4 score categorized samples as claudin-4-low or -high. Clinical and treatment data were obtained from medical records.


Claudin-4 expression was evaluated in 86 samples; 88.4% were high and 11.6% low. Mean follow-up was 98.4 months, and the local recurrence rate was 10.4%. There was a significant difference in disease-free survival between claudin-4-high and -low (4.9 and 1.9 years, respectively, P = .02); however, there was no difference between them in histologic type of recurrence (invasive or in situ) (P = .44).


In our samples, high claudin-4 expression in CIS was more frequent than low expression. Claudin-4-low expression had a worse prognosis in CIS (inferior disease-free survival), but it was similar to high claudin-4 in histologic type of local recurrence.


Breast carcinoma; Carcinoma in situ; Claudin; Survival; Tissue microarray


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