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Clinicopathological characteristics of anaplastic carcinoma of the pancreas with rhabdoid features

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Abstract

Undifferentiated (anaplastic) carcinoma with rhabdoid features is a rare and aggressive subtype of pancreatic carcinoma. Here, we report the clinical, histological, and immunohistochemical phenotypes in six autopsy cases of anaplastic carcinoma with rhabdoid features. The patients ranged between 44 and 76 years of age (median, 61 years) and consisted of four males and two females. All patients except one case died within 3 months of diagnosis, as these tumors were found at an advanced stage and were chemoresistant. At autopsy, tumor masses measuring 4–22 cm in maximum diameter were mainly located in the pancreatic body and tail. Microscopically, all cases showed anaplastic carcinoma with rhabdoid features that were discohesive with round to polygonal eosinophilic cytoplasm with occasional inclusions, and that had vesicular nuclei, and prominent nucleoli. Immunohistochemistry showed that the rhabdoid cells, particularly the inclusions, were strongly positive for pan-cytokeratin (AE1/AE3) and vimentin. Meanwhile, downregulation or aberrant cytoplasmic localization with focal aggregation of E-cadherin, β-catenin, and EMA were frequently observed in the rhabdoid cells. Moreover, the intracytoplasmic inclusions were labeled with selective autophagy-related molecules including p62/SQSTM1, ubiquitin, and kelch-like ECH-associated protein 1 (KEAP1). In addition, nuclear factor erythroid 2-related factor 2 (NRF2) and overexpression of its target molecule multidrug resistance-associated protein 1 (MRP1) were commonly observed in the rhabdoid cells. Therefore, these results suggest that p62-mediated aggregation of ubiquitinated intermediate filaments and membranous proteins is an important phenomenon in the rhabdoid phenotype. Indeed, the ubiquitinated aggregates of p62 and KEAP1 would induce activation of NRF2 and upregulation of MRP1, leading to potential chemoresistance of anaplastic carcinoma with rhabdoid features.

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Acknowledgments

The authors thank Ms. Yukari Hirotani for excellent technical support.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Division of Pathology, Department of Pathology and Microbiology, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo, 173-8610, Japan

    Makoto Sano, Taku Homma, Hiroko Noda, Yusuke Amano, Ryusuke Tsujimura, Tsutomu Yamada & Norimichi Nemoto

  2. Institute of Innovative Science and Technology, Tokai University, 143 Shimokasuya, Isehara, Kanagawa, 259-1193, Japan

    Emiko Hayashi

  3. Program in Gene Function and Expression, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA, 01605, USA

    Brian Quattrochi

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  1. Makoto Sano
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  2. Taku Homma
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Correspondence to Makoto Sano.

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Supplemental Figure 1

Histology of an INI1-negative anaplastic carcinoma case. Small-sized carcinoma cells with scant cytoplasm and crumpled nuclei (arrows) were observed in a case of INI1-negative anaplastic carcinoma (a and b, case 3) compared with INI1-positive carcinomas (c and d, cases 1; e and f, case 6). The number of pleomorphic large carcinoma cells was decreased in the INI1-negative case (PPTX 1716 kb)

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Sano, M., Homma, T., Hayashi, E. et al. Clinicopathological characteristics of anaplastic carcinoma of the pancreas with rhabdoid features. Virchows Arch 465, 531–538 (2014). https://doi.org/10.1007/s00428-014-1631-5

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  • DOI: https://doi.org/10.1007/s00428-014-1631-5

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