Author of

• 12441

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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
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12479

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    P3.06-039 - Expression of Mucin 1 in non-small cell lung cancer: Relationship between immunohistochemistry, tumour characteristics and survival (ID 2765)

    09:30 - 09:30  |  Author(s): S. Quaratino
    • Abstract

    Background
    Mucin 1 (MUC1), a glycoprotein highly expressed in many malignancies, is being explored as an antigen for immunotherapy. How best to measure MUC1 expression in non-small cell lung cancer (NSCLC) and its prognostic value in NSCLC are under discussion.

    Methods
    Tissue microarrays (TMAs) were constructed using triplicate 1mm cores of formalin-fixed paraffin-embedded tumour and stained with 214D4 (recognizes protein core) and MA695 (recognizes carbohydrate epitope) anti-MUC1 antibodies. TMAs were assessed for polarization, cytoplasmic and membranous staining intensity (scored 0–3) and proportion cells positive (0–100%; scored 0–5), averaged for multiple cores. A composite score (intensity x cells positive) was derived (range 0–15).

    Results
    TMAs from 518 patients were analyzed: 69% male, 95% Caucasian, 7% never-smoking; 49% adenocarcinoma, 35% squamous cell, 7% large cell; 43% stage I NSCLC, 33% stage II, 23% stage III. Immunohistochemistry staining intensity, proportion positive cells and depolarization were very similar between antibodies, with high concordance in composite score (R2=0.71, p<0.0001). Polarization was discordant in 8%. Similar scores were seen for N0, N1 and N2 when assessed by either antibody. For 77 cases with paired primary/N2 nodal tissue, mean 214D4 composite scores were 10.7 and 10.1 and MA695 scores 9.5 and 9.4, respectively. Discordant staining in primary but not node was seen in 5.2% and 10.4% with 214D4 and MA695, respectively. For 27 cases with neoadjuvant chemotherapy vs no chemotherapy, mean 214D4 scores were 10.2 vs 10.1 and MA695 9.3 vs 9.6, respectively. Higher scores with each antibody trended toward improved survival (non-significant). Polarization was associated with improved survival (whole cohort) with 214D4 (80.6 vs 47.8 months; HR 1.37 [95%CI 1.078–1.742], p=0.01 log rank test) and MA695 (95.8 vs 45.7 months; HR 1.48 [95%CI 1.159–1.878], p=0.002). Polarization with 214D4 was strongly associated with improved survival for adenocarcinoma (HR 1.92 [95%CI 1.385–2.668], p<0.0001) but not for non-adenocarcinoma. Similarly, polarization with MA695 conferred a survival advantage in adenocarcinoma (HR 1.68 [95%CI 1.225–2.311], p=0.001) but not non-adenocarcinoma cases. Data on MUC1 immunohistochemistry and circulating soluble MUC1 will be presented.

    	214D4	MA695
    No staining	3.5%	6.2%
    Mean intensity
    - Cytoplasmic	1.8	1.7
    - Membranous	2.1	2.2
    Mean cells positive	3.9	3.6
    Mean composite score	10.1	9.6
    - Adenocarcinoma	13.1	12.0
    - Squamous cell	7.1	7.0
    - Large cell	7.2	7.7
    Depolarization	66.7%	62.4%

    Conclusion
    Over 93% were MUC1 immunohistochemistry positive, with higher scores in adenocarcinoma. Composite scores for the two antibodies were highly correlated and depolarization largely concordant. MUC1 expression was generally maintained in paired primary/nodal tumour and was similar across nodal stages and following neoadjuvant chemotherapy. Polarization was associated with improved survival in adenocarcinoma. Further investigation is needed to determine which antibodies best predict outcomes.