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P.E. Postmus



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    P2.18 - Poster Session 2 - Pathology (ID 176)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P2.18-022 - <strong>Do <i>EGFR</i>- and <i>KRAS</i>-mutations occur in squamous cell lung carcinomas?</strong> (ID 3398)

      09:30 - 09:30  |  Author(s): P.E. Postmus

      • Abstract

      Background
      Adenocarcinoma (ADC) of the lungs may harbor EGFR- and KRAS-mutations, which are relevant for treatment decisions. Approximately 35% of non-small cell lung cancer (NSCLC) biopsies are diagnosed as not-otherwise-specified (NOS).To improve segregation between ADC and squamous cell carcinoma (SqCC), the classification of lung cancer was updated in 2011, adding immunohistochemistry (IHC) for p63 and TTF-1 to the diagnostic algorithm. The aim of our study was to investigate the hypothesis, that additional IHC reliably delineates lung cancer harboring EGFR- and KRAS-mutations.

      Methods
      From an institutional lung cancer database of specimens routinely analyzed for the presence of EGFR- or KRAS-mutations (n=816), cases harboring a mutation were selected (n=343) and corresponding original histological diagnoses and IHC for TTF-1, p63 and PAS-D were collected. Cases with a pattern compatible with SqCC were histologically reassessed.

      Results
      From the 343 cases 25% were resection specimen, 70% biopsy and 5% cytology specimens. 69% of cases had a KRAS-mutation and 31% an EGFR-mutation. IHC-data were conclusive in 89%. The combination of positive TTF-1 and/or mucin stain and a negative p63 stain, favoring ADC, was found in 264 cases (77%). Six (1.7%) specimens were positive for p63 only, favoring SqCC.

      Conclusion
      The current 2011 classification of lung tumors, based on histology and immunohistochemistry for TTF-1, p63 and mucin, segregates specimens of ADC and SqCC sufficiently well. Our study results support the use of IHC in the diagnosis of lung cancer.

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    P3.18 - Poster Session 3 - Pathology (ID 177)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Pathology
    • Presentations: 1
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      P3.18-021 - <strong>Array CGH is useful in the evaluation of patients with synchronic or metachronic tumors</strong> (ID 3380)

      09:30 - 09:30  |  Author(s): P.E. Postmus

      • Abstract

      Background
      Synchronic or metachronic tumors may develop in patients with a lung tumor. Determining whether these tumors originate from the same clone or are separate lesions may be challenging. Clinical, morphological and immunohistochemical criteria are often not distinctive. The aim of our study was to investigate comparative genomic hybridization (array CGH) analysis for the evaluation of clonality in patients with metachronic or synchronic tumors, having at least one intrathoracic tumor localization.

      Methods
      A database was constructed of consecutive patients (n=77) referred by clinicians or pathologists for assessment of clonality by array CGH from 2007 till 2012. All cases with at least one intrathoracic tumor were selected. The array CGH patterns were analyzed by a visual comparison of CGH patterns performed by two investigators and by two mathematical models on the raw data. One model uses a log likelihood ratio as described previously[1], the other a Pearson correlation between the segmented values. Clonality cut-off and p-values were set according to copy number profiles from individual patients, which are therefore by definition non-clonal. The results of the visual evaluation and the mathematical approach were correlated. A control group was formed by the specimens of one lung tumor from every patient in the database, which were all compared, using the mathematical models. 1. Ostrovnaya I, Seshan VE, Olshen AB, et al. Clonality: an R package for testing clonal relatedness of two tumors from the same patient based on their genomic profiles. Bioinformatics. 2011;27:1698-1699.

      Results
      Specimens of 77 patients were referred for analysis. Samples of 14 cases were not suited to array CGH due to insufficient material or bad quality of DNA. The remaining 63 cases comprised of 142 samples. In 8 patients DNA from more than 2 tumors was compared. In the mathematical model the outcome of 3 cases was missing, 23 cases were determined clonal, 22 non-clonal, 5 with clonal as well as non-clonal tumors and 10 were undetermined. In the negative control group > 96% of cases were scored as non-clonal. The visual analysis determined 40 cases clonal, 14 non-clonal, 1 with clonal as well as non-clonal tumors and 8 were undetermined. 46 cases were available for comparing the outcomes of the mathematical and visual evaluation, as for 3 cases data were missing and in 14 cases the outcome was undetermined. The concordance rate for clonal and non-clonal tumors between visual analysis and the mathematical approach was 35 out of 46 (76%). In 4 cases in which the visual judgment was clonal, the mathematical model determined clonal as well as non-clonal samples. In 7 cases discordance was noted: the visual outcome was clonal and the mathematical non-clonal.

      Conclusion
      Array CGH is a useful approach for evaluating clonality of synchronic or metachronic tumors.