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M. Fukayama



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    MINI 01 - Pathology (ID 93)

    • Event: WCLC 2015
    • Type: Mini Oral
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MINI01.01 - Immunohistochemical Distinction between Primary Lung Squamous Cell Carcinoma and Pulmonary Metastasis of Head and Neck Squamous Cell Carcinoma (ID 1525)

      10:45 - 12:15  |  Author(s): M. Fukayama

      • Abstract
      • Presentation
      • Slides

      Background:
      It is extremely difficult to distinguish between primary lung squamous cell carcinoma (LUSq) and pulmonary metastasis of head and neck squamous cell carcinoma (HNSq) in patients with a past history of HNSq, even by histological examination of the resected specimen. This study aimed to establish an immunohistochemical scoring system for discrimination between LUSq and pulmonary metastasis of HNSq.

      Methods:
      We selected genes that were expressed in a markedly different manner in LUSq and HNSq using the results of expression microarrays and chose the antibodies for four proteins (CK19, MMP3, ZNF830, PI3) that had immunohistochemical results shown in the Human Protein Atlas (http://www.proteinatlas.org) that were distinguishable between LUSq and HNSq. We constructed the tissue microarrays using the resected specimens of 39 LUSqs and 48 HNSqs as the training set and evaluated the tendency of HNSq using the 16-grade system according to the positive staining of the four antibodies. Twenty-seven of the patients with pulmonary tumors that were resected and pathologically diagnosed as squamous cell carcinoma between 1999 and 2014 had a past history of HNSq. Their pulmonary tumors and primary HNSqs were analyzed immunohistochemically as the test set. We defined LU-associated recurrence as postoperative recurrence in the thoracic cavity, mediastinum, brain, bone, and liver and defined HN-associated recurrence as recurrence in the other sites. We compared the diagnosis of our immunohistochemical scoring system to the preoperative clinical diagnosis and the pathological diagnosis according to the predictive power of HN-associated recurrence.

      Results:
      The sensitivity, specificity, and accuracy of our immunohistochemical scoring system were 90%, 67%, and 79%, respectively in the training set, and our system correctly diagnosed 96% of HNSq specimens in the test set. Twenty-three out of 27 pulmonary tumors in the test set were diagnosed as pulmonary metastasis of HNSq, and four were diagnosed as LUSq. Eleven of 23 patients (48%) with pulmonary metastasis of HNSq developed HN-associated recurrence (3-year HN-associated recurrence-free probability was 46%), and 10 died because of HNSq, while none of the four patients with LUSq had HN-associated recurrence. Compared with the clinical diagnosis (five LUSq, 14 pulmonary metastasis of HNSq, eight uncertain) and the pathological diagnosis (two LUSq, 17 pulmonary metastasis of HNSq, eight uncertain), our immunohistochemical scoring system could predict the risk of HN-associated recurrence more accurately. Figure 1



      Conclusion:
      Immunohistochemical analysis of four proteins (CK19, MMP3, ZNF830, PI3) was clinically useful for discrimination between LUSq and pulmonary metastasis of HNSq.

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    P1.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 233)

    • Event: WCLC 2015
    • Type: Poster
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      P1.04-019 - A Comparative Study of Micropapillary Pattern and Computed Tomographic Findings in the Patients with Small Lung Adenocarcinoma (≤ 2cm) (ID 2304)

      09:30 - 17:00  |  Author(s): M. Fukayama

      • Abstract
      • Slides

      Background:
      We have recently demonstrated that presence of the micropapillary pattern increases the risk of local recurrence after limited resection for ≤2 cm lung adenocarcinoma (ADC). Currently, limited resection for small lung ADC has been done based on the definition of radiological non-invasive lung cancer, until histological subtype have not been examination. The purpose of this study is to investigate whether the presence of micropapillary pattern correlates with radiological non-invasive lung cancer in small lung ADC.

      Methods:
      All available tumor slides from patients with clinical stage IA, therapy-naive, surgically resected solitary lung ADC ≤2 cm in size (2001-2012) were reviewed. Comprehensive histologic subtyping was performed according to the IASLC/ATS/ERS classification. Tumor diameter and solid component diameter were measured at the maximum cut surface of the tumor using high-resolution CT (HRCT). HRCT findings were classified as three groups as pure ground glass nodule (GGN), part-solid, solid based on the IASLC/ATS/ERS classification. Recurrence-free probability (RFP) was estimated using the Kaplan-Meier method.

      Results:
      233 patients met inclusion criteria (50% women; median age: 67yrs; 48% never-smokers; median tumor size: 1.2cm; 68 pure GGN/ 76 part-solid/ 89 solid; 157 lobectomy; 43 AIS/ 77 MIA/113 IAD; 13 lymph node metastasis). Presence of the micropapillary pattern (≧5%) (MPP≧5) was identified in 21 cases (9%). MPP≧5 was significantly associated with tumor size, lymph node recurrence, lymphatic invasion, vascular invasion (P = .001, .003, .0017, .014, respectively) and was associated with increased risk of recurrence as compared to MMP<5% (5-year RFP: MIP≧5%:74.3%; MIP<5%:87.6%; P = .046). Twenty-one patients with MPP≧5 included 1 pure GGN / 5 part-solid / 15 solid in HRCT. The patient with pure GGN and MPP≧5 showed recurrence in lymph nodes in 10 months after surgery. In pure GGN group, MPP≧5 was associated with increased risk of recurrence as compared to MMP<5% (P=0.0001).

      Conclusion:
      The patient with radiological non-invasive lung cancer may be included in micropapillary pattern. It is necessary to consider lung adenocarcinoma histological subtypes for the patient with limited resection.

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