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Molecular and clinicopathological analyses of esophageal carcinosarcoma with special reference to morphological change

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Abstract

The molecular pathogenesis of esophageal carcinosarcoma (ECS) has not been fully investigated. This study includes 16 consequent cases of surgically resected ECS. Genetic alterations were independently examined for carcinoma in situ, carcinomatous, and sarcomatous areas. Six cases were analyzed by next-generation sequencing, and the remaining cases were analyzed by Sanger sequencing for TP53, PTEN, and INI1. Sarcomatous components in 3 cases showed histologically heterogenous feature of osteosarcoma. Lymph node metastasis was found in 12 out of 16 cases. Survival analysis revealed 5-year overall survival rate of 59.9%, and the median survival time was 5.37 years. TP53 was the most frequently mutated gene, being identified in 11 of 16 patients (68.8%), 7 of whom (63.6%) had the same mutations in both carcinomatous and sarcomatous areas. Almost complete concordance was found between p53 immunohistochemistry and TP53 missense mutations. Five-year overall survival tended to be worse for patients with p53 overexpression, although the data was not significant (p = 0.186). Nine of 16 patients (56.3%) showed loss of heterozygosity (LOH) at the INI1 locus, and this LOH status was consistent with both components. However, interestingly, INI1 expression was preserved in all cases. In addition, copy number variation analysis revealed gene amplification in several tyrosine kinase receptors. Accumulation of mutations in tumor suppressor genes such as TP53 and INI1 seemed to occur during ECS development.

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Abbreviations

CS:

Carcinosarcoma

LOH:

Loss of heterozygosity

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Acknowledgments

We thank Noriko Sasahara, Isao Kurahayashi, Tomomi Saito, Hiroshi Sonoue, and Keiko Mitani for their excellent technical assistance. We thank the Laboratory of Molecular and Biochemical Research, Research Support Center, Juntendo University Graduate School of Medicine, for technical assistance.

Funding

This study was financially supported in part by a Grant-in-Aid for General Scientific Research from the Ministry of Education, Science, Sports, and Culture (#17K08704 to Takashi Yao and #17K08730 to Tsuyoshi Saito), Tokyo, Japan. This research was supported by AMED under Grant Number JP17am0001009.

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Authors and Affiliations

  1. Department of Human Pathology, Juntendo University School of Medicine, Hongo 2-1-1, Bunkyo-ku, Tokyo, 113-8421, Japan

    Sho Tsuyama, Tsuyoshi Saito, Yoichi Akazawa, Yuka Yanai, Noboru Yatagai, Takuo Hayashi & Takashi Yao

  2. Intractable Disease Research Center, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Tsuyoshi Saito, Yoshiyuki Suehara & Fumiyuki Takahashi

  3. Department of Gastroenterology, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Yoichi Akazawa & Noboru Yatagai

  4. Department of Orthopaedic Surgery, Juntendo University School of Medicine, Tokyo, Japan

    Keisuke Akaike & Yoshiyuki Suehara

  5. Department of Respiratory Medicine, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Fumiyuki Takahashi

  6. Department of General Thoracic Surgery, Graduate School of Medicine, Juntendo University, Tokyo, Japan

    Kazuya Takamochi

  7. Department of Esophageal and Gastroenterological Surgery, Juntendo University School of Medicine, Tokyo, Japan

    Takashi Hashimoto, Yoshiaki Kajiyama & Masahiko Tsurumaru

  8. Department of Gastroenterology and Minimally Invasive Surgery, Juntendo University Hospital, Juntendo University School of Medicine, Tokyo, Japan

    Tetsu Fukunaga

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  1. Sho Tsuyama
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Correspondence to Tsuyoshi Saito.

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This study was approved by the Ethical Committee of Juntendo University School of Medicine (2016108).

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Supplementary Fig. 1:

Copy number variations. Several gains and losses were commonly observed both in carcinoma and sarcoma components, and several differences were also observed between these components. (PNG 880 kb)

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Tsuyama, S., Saito, T., Akazawa, Y. et al. Molecular and clinicopathological analyses of esophageal carcinosarcoma with special reference to morphological change. Virchows Arch 475, 415–424 (2019). https://doi.org/10.1007/s00428-019-02643-4

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