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

• Published in: Virchows Archiv : an international journal of pathology 2019-10, Vol.475 (4), p.415-424
• Main Authors: Tsuyama, Sho, Saito, Tsuyoshi, Akazawa, Yoichi, Yanai, Yuka, Yatagai, Noboru, Akaike, Keisuke, Hayashi, Takuo, Suehara, Yoshiyuki, Takahashi, Fumiyuki, Takamochi, Kazuya, Hashimoto, Takashi, Kajiyama, Yoshiaki, Tsurumaru, Masahiko, Fukunaga, Tetsu, Yao, Takashi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Biomedical materials; Carcinosarcoma - genetics; Carcinosarcoma - mortality; Carcinosarcoma - pathology; Copy number; Esophageal Neoplasms - genetics; Esophageal Neoplasms - mortality; Esophageal Neoplasms - pathology; Esophagus; Female; Gene amplification; Heterozygosity; Humans; Immunohistochemistry; Kinases; Loss of heterozygosity; Lymph nodes; Male; Medicine; Medicine & Public Health; Metastases; Middle Aged; Missense mutation; Mutation; Next-generation sequencing; Original Article; Osteosarcoma; p53 Protein; Pathogenesis; Pathology; Protein-tyrosine kinase; PTEN protein; Quality in Pathology; Receptors; SMARCB1 Protein - genetics; Survival; Survival analysis; Tumor suppressor genes; Tumor Suppressor Protein p53 - genetics; Tyrosine
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-019-02643-4

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.