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

INTRODUCTION: 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). METHODS: A tissue microarray block, constructed from 137 pure CIS paraffin blocks, was submitted to immunohistochemical staining for claudin-4, ß-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. RESULTS: 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). CONCLUSION: 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.

Accuracy of frozen section, imprint cytology, and permanent histology of sub-nipple tissue for predicting occult nipple involvement in patients with breast carcinoma.

The sub-nipple tissue (SNT) examination has been used by surgeons to preserve, or not, the nipple in nipple-sparing mastectomy. However, it is uncertain whether SNT evaluation can predict nipple involvement. The aim of this study was to evaluate the accuracy, sensitivity, specificity, PPV, and NPV of the intraoperative frozen section and imprint cytology, and permanent histology of SNT to predict the involvement of the nipple in breast carcinoma and to compare the three exams. A prospective study was performed with 68 consecutive breast carcinoma women who had undergone mastectomy or central segmentectomy (removing nipple-areolar complex). After surgery, the nipple-areolar complex was dissected simulating a nipple-sparing flap (ex vivo). The SNT was subsequently removed and submitted to frozen section, imprint cytology, and permanent histology. The nipple was examined separately by paraffin histopathology and was considered the gold standard. The occult nipple involvement rate was 11.7 %. The frozen section, cytology, and permanent histology of SNT presented accuracy 86.8, 76.5, and 86.8 %; sensitivity 50, 37.5, and 62.5 %; specificity 91.7, 81.7, and 90 %; PPV 44.4, 21.4, and 45.5 %; and NPV 93.2, 90.7, and 94.7 %, respectively. The accuracy of the frozen section was similar to that of permanent histology (p = 0.77) and both were better than cytology (p = 0.01). False negative rates were 6.8 % for frozen section, 9.3 % for cytology and 5.3 % for paraffin. SNT evaluation is a good method for predicting occult nipple involvement; the outcomes showed a good accuracy and low false negative rate for the frozen section, cytology, and permanent histology exams. When we compared the exams, the frozen section was similar to permanent histology and more accurate than imprint cytology.