Author of

• 15382

  +

  P3.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 235)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/09/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 15454

    +

    P3.04-072 - Overexpression of CADM1 Is Associated with Poor Prognosis in Small Cell Lung Cancer (ID 2670)

    09:30 - 09:30  |  Author(s): M. Onizuka
    • Abstract

    Background:
    CADM1, a member of the immunoglobulin superfamily cell adhesion molecules, acts as a tumor suppressor in a various cancers, including non-small cell lung cancer (NSCLC). In contrast, CADM1 also acts as an oncoprotein that promotes invasion in ATL and small cell lung cancer (SCLC) cells. Here, we investigate the possible association of CADM1 expression and splicing variant with the clinical characteristics of surgically treated patients with primary lung cancer.
    
    Methods:
    Expression and splicing variant of CADM1 was examined by RT-PCR, Western blotting, immunohistochemistry, and SSCP, respectively. We studied splicing variant of CADM1 in 5 primary NSCLC tumors and a primary SCLC tumor, as well as 16 SCLC and 10 NSCLC cell lines. Immunohistochemical expression of CADM1 was analyzed in 34 primary SCLC tumors and 25 primary NSCLC tumors. Statistical analysis was performed to determine significant predictor for overall survival and recurrence-free survival.
    
    Results:
    Western blotting and RT-PCR analyses have revealed that CADM1 is significantly expressed in 11 of 14 SCLC cells growing in suspension cultures but in neither of 2 SCLC cells showing attached growth to plastic dishes, suggesting that CADM1 is involved in anchorage-independent growth in SCLC. Then, we demonstrate that SCLC expresses a unique splicing variant of CADM1 (variant 8/9) containing additional extracellular fragments corresponding to exon 9 in addition to variant 8, a common isoform in epithelia. Variant 8/9 of CADM1 is almost exclusively observed in SCLC and testis, although this variant protein localizes along the membrane and shows similar cell aggregation activity to variant 8. Interestingly, both variant 8/9 and variant 8 of CADM1 show enhanced tumorigenicity in nude mice when transfected into SBC5, a SCLC cell lacking CADM1. Inversely, suppression of CADM1 expression by shRNA reduced spheroid-like cell aggregation of NCI-H69, a SCLC cell expressing a high amount of CADM1. These findings suggest that CADM1 enhances the malignant features of SCLC, as is observed in ATL. Immunohistochemistry demonstrates that CADM1 is strongly expressed in 24 of 34 (71%) SCLC and 2 of 25 (8%) NSCLC, weakly expressed in 7of 34 (21%) SCLC and 10 of 25 (40%) NSCLC, and negative in 3 of 34 (9%) SCLC and 7 of 16 (44%). In NSCLC, loss of CADM1 expression was preferentially observed in heavy smokers (smoking index ≥ 800). In SCLC, overexpression of CADM1 was significantly associated with poor prognosis in surgical patients.
    
    Conclusion:
    SCLC represents high recurrence rates and poor clinical outcome. Surgical treatment can achieve satisfactory results in selected cases. Overexpression of CADM1 could be an indicator of poor prognosis and could influence the decision for adjuvant therapy or follow up intervals in surgical patients with SCLC.