Abstract 5449: Calretinin can be the specific marker for phyllodes tumor
Authors: Ishiba Tohiyuki , Aruga Tomoyuki , Nara Miyako , Yabe Sakiko , Saita Chiaki , Onishi Mai , Iwamoto Naoko , Yonekura Rika , Miyamoto Hiromi , Honda Yayoi , Oda Goshi , Nakagawa Tsuyoshi , Nakanishi Akira , Uetake Hiroyuki , Miki Yoshio 
Published: September 2020

Abstract
Background Rare phyllodes tumors (PT) comprise a mixture of stromal and epithelial cells, and they can acquire malignant potential, which results in rapid progression and metastasis. Therefore, PT should be resected with an adequate free margin for curative intent. Fibroadenoma (FA) is a benign type of tumor that rarely becomes malignant, and usually does not require resection. However, PT and FA are morphologically and pathologically similar, which makes them difficult to distinguish in clinical practice. Thus, we aimed to determine a means of distinguishing them using a proteomic approach called Isobaric Tag for Relative and Absolute Quantitation (iTRAQ). We added different isobaric tags to normal and phyllodes tumor tissues, detected proteins using a database search and selected those that were at least three-fold more abundant than in normal tissue. Among them, we found high expression levels of calretinin, a specific marker for mesothelioma, in PT.
Methods Tissue specimens were collected from 36 patients with PT (benign, n = 16; borderline, n = 15; malignant, n = 5), from 37 with FA and from three local recurrence sites of PT. All patients were treated by surgical resection at the Department of Breast Surgery, Tokyo Medical and Dental University, Japan, between March 2003 and August 2012. The specimens were analyzed by immunohistochemistry (IHC) using a calretinin antibody, and malignant mesothelioma as a positive control. Immunostaining for calretinin was analyzed by light microscopy in three high-power fields (HPF) and calretinin expression was assessed using Allred scores calculated on a scale from 0 to 8 as proportion (PS) plus intensity (IS) scores. We defined Allred scores of 0 and 2 as low (CLG) and those &gt; 3 as high (CHG) calretin as reported for malignant mesothelioma. Data were analyzed using chi-square tests.
Results All samples were stained. Stromal, but not epithelial cells tended to be positively stained for calretin. We found 20 and 17 FA, and 9 and 27 PT in CLG and CHG, respectively. More calretinin was expressed in PT than in FA (p = 0.011). Six and 25 benign or borderline PT were found in CLG and CHG, respectively. More calretinin was expressed in benign and borderline PT than in FA (p = 0.006). Three patients had local recurrence and one had distant metastasis. Recurrence did not significantly correlate with calretinin expression in PT; calretinin expression was low in all instances of local recurrence.
Conclusion We found that calretinin could distinguish between PT and FA and could therefore function as an important marker when planning surgery. Malignant PT and sites of local recurrence tended to express low levels of calretinin. Further investigation of calretinin with PT and FA is needed.
Citation Format: Tohiyuki Ishiba, Tomoyuki Aruga, Miyako Nara, Sakiko Yabe, Chiaki Saita, Mai Onishi, Naoko Iwamoto, Rika Yonekura, Hiromi Miyamoto, Yayoi Honda, Goshi Oda, Tsuyoshi Nakagawa, Akira Nakanishi, Hiroyuki Uetake, Yoshio Miki. Calretinin can be the specific marker for phyllodes tumor [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5449.