Abstract P5-17-10: Claudin -4 expression in carcinoma in situ and its association with local recurrence, clinical and immunohistochemistry characteristics
Authors: Duarte GM , Toucchet F , Espinola JP , Barreto CR , Paiva Silva GR , Almeida NR , Soares F , Pinto G , Marshall P 
Published: May 2016

Abstract
Introduction: Claudins are tight junction molecules and 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, it is unknown whether Claudins expression could be associated to carcinoma in situ prognostic. The aim of this study was evaluated 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, estrogen receptor (ER), progesterone receptor (PR), HER-2 and Ki-67. It was calculated Claudin-4 score based in percentage and intensity of expression and categorized in: Claudin-4 low and Claudin – 4 high. The clinical data, treatment data (surgery, radiotherapy and tamoxifen use), local recurrence data (date and type) and death of each patient were reviewed in the medical records. The statistical analyze used Kaplan-Meier curve and log-rank test to disease free survival; qui-square and Fisher test to compare others variables; significance level of 5 % was used.
Results: It was possible to evaluate Claudin-4 expression in 86 cases, 88.4% were Claudin-4 high and 11.6% Claudin-4 low. The follow up mean was 69 months and local recurrence rate was 10.5 %. There was no significant difference in local recurrence rate between Claudin-4 high and Claudin-4 low (10.0% x 10.5% , p=1.0).The disease free survival was similar between Claudin-4 low and Claudin-4 high (p=0.559). The Claudin- 4 high was significantly more frequent in beta-catenin positive patients (p=0.048). There was no association significantly between Claudin-4 expression and: age (p=0.66), histology type (p=0.75), surgery (p=0.102), radiotherapy (p=0.29), tamoxifen use (p=0.432), ER (p=0.33), PR (p=1.0), HER-2 (p=0.23) and e-caderin (p=0.21).
Conclusion: Despite the Claudins are related to invasive carcinoma prognosis, our outcome did not show difference in local recurrence and disease free survival between Claudin-4 low and high in carcinoma in situ. The beta-catenin and claudin-4 expressions were significantly associated.
Citation Format: Duarte GM, Toucchet F, Espinola JP, Barreto CR, Paiva Silva GR, Almeida NR, Soares F, Pinto G, Marshall P. Claudin -4 expression in carcinoma in situ and its association with local recurrence, clinical and immunohistochemistry characteristics. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-10.