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Han Si



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    P1.09 - Pathology (ID 173)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Pathology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.09-12 - In-Situ Hybridization Visual Scoring of Epigenetic Imprinting Genes Improves Early Diagnosis and Grading of Lung Cancers (Now Available) (ID 1504)

      09:45 - 18:00  |  Author(s): Han Si

      • Abstract
      • Slides

      Background

      Pathologists rely on cellular morphology to determine cancer diagnosis. However earlier grades (dysplasia) and stages (Carcinoma-in-situ) of cancers which are most treatable have less obvious changes. Epigenetic changes occur at most stages of carcinogenesis, but the application of epigenetic testing in cancer diagnosis is limited. Imprinted genes are normally silenced in one of two parental alleles, but is reportedly reversed in carcinogenesis, with expression of biallelic (Loss of Imprinting-LOI) or multiallelic (Copy Number Variations-CNV) expression (Figure 1A). We present here a novel visual and quantitative approach targeting imprinted genes involved in lung cancer development and progression.

      Method

      The Lisen in-situ hybridization(ISH) targets non-coding introns of imprinted genes to provide a visual and quantitative analysis of malignancy associated changes, unlike bisulfite reduction techniques. Formalin fixed lung cancer and benign lung samples are tested with an epigenetic panel (imprinted genes GNAS, GRB10 and SNRPN) stains. Diagnostic algorithm for a grading model based on LOI, CNV and summed “Total Expression (TE)” counts is developed comparing cancer samples in different stages and benign samples (Figure 1A).

      wclc abstract figure - rex yung.jpg

      Result

      Technicians trained in counting LOI and CNV studied 198 cases of lung samples in a blinded fashion to score LOI, CNV and TE (Figure 1A). These included 29 benign, 20 with Atypical Adenomatous Hyperplasia (peripheral), 11 Adenocarcinoma-in-situ (ADIS), 138 invasive squamous and adenocarcinomas (64 stage 1, 20 stage 2, 54 stages 3&4). A grading model from Grade 0 (benign) to Grade IV (highly malignant) is developed based on the expression pattern of the three genes epigenetic panel to correlate with pathological staging. Grade 0 (benign) corresponds with benign normal, Grade I (malignant potential) corresponds with precancerous AAH, Grade II (limited disease) corresponds to ADIS, Grade III (more invasive) corresponds to stage 1 and 2, and Grade IV (highly invasive) corresponds to stages 3 and 4. (Figure 1B)

      Conclusion

      Imprinted gene detection by ISH staining provides a novel way to visualize and quantify epigenetic changes occurring in earlier stages of lung cancer development. The quantitative grading model can reduce the subjective variation in diagnosis and provide a more precise tool to assist the pathologist. Inclusion of an expanded panel of imprinted genes, studying larger specimen sets and adaptation by automated image analysis hold promise of advancing standardization of early lung cancer diagnosis.

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    P2.03 - Biology (ID 162)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Biology
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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      P2.03-54 - Imprinted Genes Predict Non-Small Cell Lung Cancer Prognosis (Now Available) (ID 1214)

      10:15 - 18:15  |  Author(s): Han Si

      • Abstract
      • Slides

      Background

      Lung cancer (LC) is the leading cause of cancer mortality worldwide, Significant numbers of stage I/II patients after curative surgery present with recurrent and progressive disease. It is critical to identify additional biomarkers to predict prognosis of early stage NSCLC. In carcinogenesis, epigenetic modifications on imprinted genes are changed and lead to biallelic (loss of imprinting, LOI) and multiallelic (copy number variation, CNV) expression. We present here an epigenetic panel involved in NSCLC prognosis.

      Method

      Retrospective study of 123 NSCLC cases with known 5-year survival status. Samples from diagnostic bronchoscopies are subjected to in-situ hybridization targeting non-coding regions to show the expression status of imprinted genes. Total expression (TE), LOI and CNV are counted manually. A statistical model is generated based on the expression status of a 3-imprinting gene epigenetic panel (DCN, PEG10 and SNRPN) to classify the cases. The 5-year survival is used as the only standard for good or poor prognosis.

      Result

      The NSCLS cases can be classified into 4 groups by epigenetic panel. In group A with high expression of DCN, 91.2% (31/34) had poor prognosis, including 8 stage I, 6 stage II, 9 stage III and 8 stage IV. In group B with low expression of DCN and high expression of both PEG10 and SNRPN, 75% (6/8) had poor prognosis. In group C with low expression of DCN and low expression of either or both of PEG10 and SNRPN, 39.5% (30/76) had poor prognosis. In group D with no expression of DCN, PEG10 or SNRPN, 100% (5/5) had good prognosis, even when metastatic and recurrent cases are found, their average survival is more than 8 years.

      Conclusion

      Imprinting Gene epigenetic panel may provide a quantitative assessment of NSCLC prognosis, and complement standard pathologic staging. This explains the poor prognosis of some early stage ca. The prognostic role may help select individual cases for adjuvant therapies. Further studies with expanded epigenetic panel and larger patient sets are planned to refine the classification algorithm, and identify potential predictive biomarkers for specific therapies to advance personalized lung cancer care.

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