CLAUDIN-4 EXPRESSION IN CARCINOMA IN SITU AND ITS ASSOCIATION WITH LOCAL RECURRENCE, CLINICAL AND IMMUNOHISTOCHEMISTRY CHARACTERISTICS.

Introduction: Claudins are tight junction molecules and nowadays have been associated to breast cancer prognosis. Claudin-low intrinsic subtype of invasive carcinoma was described recently and has been related to high grade carcinoma, low junction molecules expression and worse chemotherapy response. However, there is no data about Claudins expression and carcinoma in situ prognostic. The aim of this study was evaluate the Claudin-4 expression in carcinoma in situ and its association with local recurrence, clinical and immunohistochemistry characteristics. Methods: A Tissue Microarray (TMA) block was constructed using region of interesting, with 137 pure carcinoma in situ paraffin blocks of patients treated in the Women `s Hospital Prof. Dr. José Aristodemo Pinotti? UNICAMP from 1999 to 2009. The TMA was submitted to immunohistochemistry analyze to Claudin-4, beta-catenin, e-caderin, hormone receptors, HER-2 and Ki-67. It was calculated claudin-4 score based in percentage and intensity of expression and categorized in: low and high. The clinical, surgical, radiotherapy, hormoniotherary, recurrence and death data of each patient were reviewed in the medical records. The statistical analyze used Kaplan-Meier curve and log-rank test to survival, qui-square and Fisher test and significance level of 5 %. Results: It was possible to evaluate Claudin-4 expression in 86 cases, 88.4% had high expression and 11.6% low expression. The follow up mean was 5.77 years. There was no significant difference in disease-free survival between low and high Claudin-4 expression (p=0.559), age (p=0.66), histology type (p=0.75), ER (p=0.33), PR (p=1.0), HER-2 (p=0.23) and e-caderin (p=0.21). The Claudin- 4 was just correlated with beta-catenin expression (p=0.048). Conclusion: Despite the Claudins be related to invasive carcinoma prognosis, our outcome did not show difference in carcinoma in situ local recurrence between low and high Claudin-4 expression. The beta-catenin and Claudin-4 expressions were significantly associated.