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Kentaro Inamura



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    P1.06 - Mesothelioma (ID 169)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Mesothelioma
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.06-11 - Overlapping Immunophenotypes Between Mesothelioma and Angiosarcoma: Usefulness of Claudin-5 in the Differential Diagnosis (ID 240)

      09:45 - 18:00  |  Author(s): Kentaro Inamura

      • Abstract
      • Slides

      Background

      Differential diagnosis between mesothelioma and angiosarcoma remains challenging because of their overlapping morphological and immunohistochemical phenotypes. Angiosarcoma may show both epithelioid and sarcomatoid morphology and is occasionally a cytokeratin-expressing tumor as with mesothelioma. Generally, endothelial markers are always expressed by angiosarcoma but not by mesothelioma; however, a subset of mesothelioma expresses endothelial markers, making the usefulness of these markers limited. Currently, little information is available about the immunoreactivity of mesothelioma to endothelial markers. Therefore, we investigated immunoreactivities of mesothelioma and angiosarcoma to endothelial markers and sought to identify a useful marker in their differential diagnosis.

      Method

      We enrolled 147 cases of pleural mesothelioma, comprising 93 epithelioid, 25 biphasic, and 29 sarcomatoid subtypes. For comparison, we used 41 cases of angiosarcoma occurring in various organs. Using a tissue block showing the representative morphology, the expressions of endothelial (CD31, CD34, factor-VIII, ERG, and claudin-5) and of mesothelial markers (calretinin, WT-1, CK5/6, and EMA) were evaluated by immunohistochemistry.

      Result

      Calretinin and WT1 were expressed in 82.2% (120/146) and 82.9% (116/140) cases of mesothelioma, respectively. Among the three subtypes of mesothelioma, the immunoreactivity of sarcomatoid mesothelioma to calretinin was relatively low with the positivity of 48.3% (14/29). Calretinin was expressed in none of the angiosarcoma cases (0/41), whereas WT-1 was expressed in 4.9% (2/41) cases of angiosarcoma. Conventional endothelial marker (CD31, CD34, factor VIII, and ERG) were expressed in 10.3% (15/146), 3.5% (5/142), 3.4% (5/146), and 29.1% (39/134) cases of mesothelioma, respectively. The immunoreactivities of sarcomatoid mesothelioma to conventional endothelial markers were relatively high with the positivity of 31.0% (9/29) for CD31, 7.1% (2/28) for CD34, 10.7% (3/28) for factor VIII, and 56.0% (14/25) for ERG. Claudin-5 expression was observed in all the angiosarcoma cases (36/36), but in none of the mesothelioma cases (0/138).

      Conclusion

      We showed overlapping immunophenotypes between mesothelioma and angiosarcoma. Endothelial markers, except for claudin-5, were more frequently expressed than expected by mesothelioma, especially by sarcomatoid mesothelioma. High sensitivity and specificity of claudin-5 in the distinguishment of angiosarcoma from mesothelioma suggest the usefulness of this marker, indicating that claudin-5 should be included in a panel of immunohistochemical markers in the differential diagnosis between mesothelioma and angiosarcoma.

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    P2.09 - Pathology (ID 174)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.09-10 - INSM1 Is a Good Marker for Diagnosis of Small Cell Lung Carcinoma Even When Neuroendocrine Marker Negative (Now Available) (ID 1104)

      10:15 - 18:15  |  Author(s): Kentaro Inamura

      • Abstract
      • Slides

      Background

      To diagnose small cell lung carcinoma (SCLC), neuroendocrine (NE) phenotype markers such as chromogranin A, synaptophysin and CD56 are helpful. However, because they are dispensable, SCLCs occur without neuroendocrine phenotypes. Insulinoma-associated protein 1 (INSM1) is a transcription factor for neuroendocrine differentiation and has emerged as a single practical marker for SCLC.

      Method

      Using the surgical samples of 141 NE tumors (78 SCLCs, 44 large cell neuroendocrine carcinomas (LCNECs), and 19 carcinoids), and 246 non-NE carcinomas, we examined the immunohistochemical expression and prognostic relevance of INSM1 in association with NE phenotype markers in each histologic type. We evaluated its sensitivity and specificity for SCLC diagnosis, as well as its usefulness to diagnose SCLC without NE marker expression and to estimate the prognosis of the subgroups of SCLC stratified by the expression levels of the NE markers. Those of 13 lung cancer cell lines (9 SCLCs and 4 ADCs) were also evaluated.

      Result

      INSM1 was expressed in SCLCs (92%, 72/78), LCNECs (68%, 30/44), and carcinoids (95%, 18/19). Additionally, among SCLCs with no expression of NE phenotype markers (n=12), 9 (75%) were positive for INSM1. These data suggest the superiority of INSM1 to the phenotype markers. SCLC with low INSM1 expression (n=28) had a significantly better prognosis (P=0.040) than the high-INSM1 group (n=50). Only 7% of adenocarcinomas (9/134) and 4% of squamous cell carcinomas (4/112) were positive for INSM1. In cell lines, most SCLCs were positive for INSM1 (7/9), whereas all ADCs were negative (0/4).

      Conclusion

      Our study revealed that INSM1 is highly sensitive to detect SCLC, is positive in most phenotype marker-negative SCLCs and can estimate prognosis. INSM1 will be a promising marker for SCLC. 

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