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Hironori Ninomiya
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MA18 - Advances in Diagnosis of Common Types of NSCLC (ID 145)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Pathology
- Presentations: 1
- Now Available
- Moderators:Yuko Minami, Mary Beth Beasley
- Coordinates: 9/10/2019, 11:30 - 13:00, Tokyo (1982)
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MA18.03 - Distinction Between Primary Lung Cancer and Pulmonary Metastasis of Esophageal Cancer Using the Nanostring nCounter System (Now Available) (ID 1228)
11:30 - 13:00 | Author(s): Hironori Ninomiya
- Abstract
- Presentation
Background
It is very difficult to distinguish between primary lung squamous cell carcinoma (LSCC) and pulmonary metastasis of esophageal squamous cell carcinoma (ESCC) in patients with past history of ESCC, even by histological examination of the resected specimen. This study aimed to distinguish between LSCC and metastasis of ESCC by multiplex gene expression analysis using the Nanostring nCounter analysis system.
Method
RNA was extracted from the FFPE samples of eight LSCCs, thirteen ESCCs, and nine indeterminate SCCs in the lung of patients with history of ESCC. We selected ten genes which were differently expressed markedly between LSCC and ESCC using the nCounter PanCancer Pathways Panel (XT-CSO-PATH1-12). We performed linear discriminant analysis between the two groups. The derived discriminant function was applied to the nine indeterminate SCCs. The nCounter diagnosis was compared to the preoperative features, pathological findings and postoperative prognosis.
Result
Four of nine pulmonary tumors were diagnosed as LSCC and five were diagnosed as metastasis of ESCC. None of four patients with LSCC died and one developed recurrence, while all of five patients with metastasis of ESCC died and all developed recurrence. The prognosis of the latter was significantly poorer than the former (logrank test, p = 0.02). The preoperative features which indicate metastasis of ESCC (multiple lesions, short disease-free interval and presence of local recurrence) were found only in the metastasis group.
Conclusion
Multiplex gene expression analysis using the nCounter was useful for discrimination between LSCC and pulmonary metastasis of ESCC.
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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): Hironori Ninomiya
- Abstract
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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P1.09 - Pathology (ID 173)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Pathology
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.09-20 - Significance of Maximal Diameter Measurement in Small-Sized Adenocarcinomas (ID 2168)
09:45 - 18:00 | Presenting Author(s): Hironori Ninomiya
- Abstract
Background
8th edition of the TNM classification for lung cancer has been available since Jan. 2017. The changes are based on a new database of about 90 000 evaluable patients with lung cancer. The proposed changes primarily reflect stratification of patients with lung cancer into prognostically more-precise categories. The revision includes new tumor-size criteria and better-defined classification of additional tumor nodules, subclassifications of lymph node, and systemic metastases. However, invasive size measurement is difficult in some cases, so interobserver variability is inevitable. A maximal size measurement can reduce the interobserver variability to assess the small tumors. To clarify the significance of the maximal diameter measurement, small-sized tumors (10mm or less in maximal diameter) was also subclassified and prognosis after surgery was compared with conventional classification. In addition, we identified the characteristics of small-sized tumor with a worse prognosis.
Method
Pulmonary adenocarcinoma treated surgically at our hospital between Jan. 2006 and Dec. 2011 were recruited. All the cases were evaluated according to the 8th TNM classification. Subsequently, the group with maximal diameter 10mm or less were subcategorized. The Kaplan-Meier method was used to calculate survival. Moreover, clinicopathological characteristics of recurrent cases were also reviewed.
Result
Tumors with 10mm or less maximal diameter comprised 33.6% (94/288) of pTis, pT1mi and pT1a tumors. Average maximal diameter did not differ statistically between pT1mi and pT1a groups (P=0.38). Prolapse-free and disease-specific survivals of the cases with maximal diameter 10mm or less tumors without nodal metastasis were 98.8% and 100%, respectively. Only two cases with maximal diameter 10mm or less tumors recurred (2%, 2/94), both being solid type on CT image and one of the two cases exceptionally showed vascular and pleural invasion as well as nodal metastasis. The maximal diameter of recurrent cases clustered around the value of 10mm.
Conclusion
Only a small fraction of tumors with maximal diameter 10mm or less recurred in our series. Since the recurrent cases clearly showed particular findings including vascular and pleural invasion and a solid image on CT, they can be differentiated from other tumors pathologically or by CT. The maximal diameter measurement is useful in tumors with 10mm diameter or less to estimate the tumor prognosis.
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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): Hironori Ninomiya
- Abstract
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.
