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Claudin-3 and Claudin-4: Distinct Prognostic Significance in Triple-Negative and Luminal Breast Cancer

Kolokytha, Panagiota MD*; Yiannou, Petros MD; Keramopoulos, Dimitris MD; Kolokythas, Argyrios MS-V§; Nonni, Afroditi MD, PhD*; Patsouris, Efstratios MD, PhD*; Pavlakis, Kitty MD, PhD*

Applied Immunohistochemistry & Molecular Morphology: February 2014 - Volume 22 - Issue 2 - p 125–131
doi: 10.1097/PAI.0b013e31828d9d62
Research Articles

Introduction: To investigate the immunohistochemical expression of claudin-1, claudin-3, and claudin-4 in triple-negative breast carcinomas and compare it with several clinicopathologic parameters as well as their expression in luminal cancers.

Materials and Methods: A total of 128 cases of breast carcinoma were included in the study. For all these cases, immunohistochemistry for estrogen and progesterone receptors, Ki-67, and Her2 had already been performed, whereas Her2 2+ cases had been further characterized as positive or negative for Her2 amplification with the chromogenic in situ hybridization technique. Seventy-six tumors were triple negative. The remaining 52 were luminal cancers. All tumors were evaluated for the expression of claudin-1, claudin-3, and claudin-4.

Results: In the triple-negative group, the positive expression of claudin-3 and claudin-4 was related to unfavorable and favorable prognostic factors, respectively. Claudin-1 was not related to any parameter under evaluation. In the luminal cancer group, claudin-4 positivity was related to a shorter disease-free survival, whereas the inverse was observed for claudin-3. Moreover, all 3 claudins increased with increase of the grade and Ki-67 value in the luminal cancers.

Conclusion: A distinct prognostic significance in the expression of claudin-3 and mostly of claudin-4 between triple-negative and luminal breast carcinomas was identified. Specifically, in triple-negative carcinomas, claudin-4 positivity could probably be considered as a biomarker of favorable prognosis, whereas in luminal cancers with claudin-4-positive expression, the administration of targeted therapy should eventually be part of the patients’ management in the near future.

*1st Pathology Department

§Medical School, National and Kapodistrian University of Athens

Department of Pathology

Breast Cancer Unit, “IASO” Women’s Hospital, Athens, Greece

The authors declare no conflict of interest.

Reprints: Panagiota Kolokytha, MD, 33 Paflagonon Street, Nea Penteli, Attica 15236, Greece (e-mail:

Received November 7, 2012

Accepted February 14, 2013

© 2014 Lippincott Williams & Wilkins, Inc.