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S. Neri

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    MO26 - Anatomical Pathology II (ID 129)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Pathology
    • Presentations: 1
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      MO26.12 - Prognostic Impact of Microscopic Vessel Invasion and Visceral Pleural Invasion in Non-small Cell Lung Cancer (ID 2480)

      10:30 - 12:00  |  Author(s): S. Neri

      • Abstract
      • Presentation
      • Slides

      In non-small cell lung cancer (NSCLC), visceral pleural invasion (VPI) is incorporated as a staging factor in the current TNM classification. Microscopic vessel invasion (MVI: defined collectively as histological blood vessel invasion and lymphatic permeation) has been reported to be a strong independent predictor of poor prognosis, but it has not been incorporated in the TNM classification. We assessed the prognostic significance of MVI as well as VPI.

      Between August 1992 to December 2009, 2657 consecutive patients with pathological T1-4N0-2M0 NSCLC underwent complete resection at our institution. We analyzed the prognostic significance of MVI for recurrence in addition to the conventional prognostic factors. The recurrence-free proportion was estimated using the Kaplan-Meier method and differences were analyzed by the log-rank test. Cox regression analyses were used to identify independent risk factors for recurrence.

      The 5-year recurrence-free proportion for patients with or without MVI was 52.6% and 87.5%, respectively (p < 0.001). On multivariate analysis, MVI, similarly to VPI, was found to be an independently significant predictor of recurrence (HR 2.78). In 1601 patients with pathological stage I disease without adjuvant chemotherapy, MVI and VPI were the two strongest independent predictors of recurrence on multivariate analysis (HR 2.74 and 1.84, respectively). Evident and significant separation of the recurrence-free proportion curves among the following 3 groups according to the number of the two risk factors (VPI and MVI) was observed; both VPI and MVI absent (0), either VPI or MVI present (1), and both VPI and MVI present (2). We compared the recurrence-free proportion of patients stratified by tumor size and the number of the risk factors (0/1/2) (Table 1). The groups of small tumor size without PL and MVI showed the best recurrence-free proportions (T1a_0, T1b_0, and T2a_0). The T1a_1, T1b_1, and T2a_1 subgroups showed poorer outcomes which were comparable with the T2b_0 subgroup. The groups with both PL and MVI, even in small tumor size groups, resulted in poor outcomes equivalent to that of T3_0/1 groups. The T3_2 group showed the poorest outcome equivalent to the T4 group.

      This study demonstrated that MVI was a significantly independent risk factor for recurrence in resected T1-4N0-2M0 NSCLC patients. We propose the T-classification of tumors with either MVI or VPI (1) should be upgraded to the next T level and that with both MVI and VPI (2) to the second T level (Table 1).

      Table 1. Incorporation of PL and MVI into T classification
      Current (7th) T Classification Tumor Size (cm) No. of VPI and MVI Risk Factors Recurrence-free Proportion at 5 Years (%) OurProposalT
      T1a ≤ 2 0 92.2 T1
      ≤ 2 1 72.2 T2
      ≤ 2 2 58.2 T3
      T1b > 2, ≤ 3 0 89.6 T1
      > 2, ≤ 3 1 64.8 T2
      > 2, ≤ 3 2 50.9 T3
      T2a > 3, ≤ 5 0 87.8 T1
      > 3, ≤ 5 1 61.9 T2
      > 3, ≤ 5 2 44.8 T3
      T2b > 5, ≤ 7 0 75.9 T2
      > 5, ≤ 7 1 49.4 T3
      > 5, ≤ 7 2 47.5 T3
      T3 > 7 0 58.2 T3
      > 7 1 50.6 T3
      > 7 2 38.8 T4

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    P3.06 - Poster Session 3 - Prognostic and Predictive Biomarkers (ID 178)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P3.06-050 - Characteristic Immunophenotype of Solid Subtype Component<br /> in Lung Adenocarcinoma (ID 3289)

      09:30 - 16:30  |  Author(s): S. Neri

      • Abstract

      Lung adenocarcinomas represent a morphologically heterogeneous tumor composed of an admixture of different histologic subtypes (lepidic, papillary, acinar, and solid subtype). The presence of a solid subtype component is reported to be associated with a poorer prognosis. The aim of this study was to evaluate the characteristic immunophenotype of the solid subtype component compared with the immunophenotypes of other components.

      We analyzed the clinicopathological characteristics of stage I adenocarcinoma patients with predominant solid subtype disease. Furthermore, we immunostained adenocarcinomas with predominant lepidic, papillary, acinar, and solid subtype components (n = 23 each) for 10 molecular markers of tumor invasiveness and scored the results.

      Patients showing predominance of the solid subtype component (solid subtype adenocarcinoma) had a poorer prognosis than those showing predominance of the lepidic, papillary, or acinar component. Lymphovascular invasion was more often detected in solid subtype tumors than in others. The solid subtype component showed a significantly stronger staining intensity of laminin-5 expression than the lepidic, papillary, and acinar components (P\\0.001, P\\0.001, and P = 0.016, respectively). The fibronectin and vimentin expression levels were also significantly higher in the solid subtype component than in other components. This immunostaining character was validated by using mixed-subtype adenocarcinomas containing all four components in the same tumor.

      This study concluded that the solid subtype component in lung adenocarcinomas exhibit the invasive immunophenotype, including increased laminin-5 expression, compared with the other components, which may be associated with a poorer prognosis.