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J.N. Jakobsen



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    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P1.06-002 - Intratumor variation of biomarker expression by immunohistochemistry in resectable non-small cell lung cancer (ID 134)

      09:30 - 16:30  |  Author(s): J.N. Jakobsen

      • Abstract

      Background
      Prognostic and predictive biomarkers are increasingly used to customize treatment of patients with solid tumors. Intra- and inter-tumor heterogeneous distribution of biomarker expression are potential confounders for use of biomarkers, as small biopsies may not necessarily truly reflect the pattern of biomarker expression. It may also be an important factor in chemoresistance, as tumors with heterogeneous biomarker expression may potentially harbor chemoresistant tumor clones.

      Methods
      Immunohistochemical evaluation of expression of excision repair cross complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), class III-β-tubulin (TUBB-3), Thymidylate synthase (TS), Ki-67 and ribonucleotide reductase M1 (RRM1) was performed in 15 separate areas in each of 6 small microscopically completely resected adenocarcinomas of the lung in order to elucidate any heterogeneous distribution.

      Results
      Clinically relevant biomarker heterogeneity with respect to expression of EGFR, ERCC1, RRM1, TUBB-3, and Ki-67 was observed in 4 (66%), 4 (66%), 2 (33%), 3 (50%) and 5 (83%) out of 6 tumors, respectively. Thus, heterogeneity could potentially allocate these tumors erroneously into high or low expressers by chance alone, according to previously reported cut-off values. In contrast, TS was almost completely homogenously distributed.

      Conclusion
      Most biomarkers examined, except for TS, showed clinically significant intratumor heterogeneity in 33% to 87% of tumors examined. This heterogeneity may influence results in studies investigating the therapeutic impact of predictive biomarkers in NSCLC.

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    P2.06 - Poster Session 2 - Prognostic and Predictive Biomarkers (ID 165)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
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      P2.06-020 - Pretreatment thymidylate synthase protein expression levels remains stable during paclitaxel and carboplatin treatment in non-small cell lung cancer (ID 1945)

      09:30 - 16:30  |  Author(s): J.N. Jakobsen

      • Abstract

      Background
      Thymidylate synthase (TS) is a potential predictive marker for efficacy of treatment with pemetrexed. The current study aimed at investigating whether TS expression changes during non-pemetrexed chemotherapy of non-small cell lung cancer (NSCLC) thus making rebiopsy necessary for deciding on pemetrexed second line treatment.

      Methods
      TS immunohistochemístry was performed on biopsies and available resection specimens from 65 NSCLC patients stage T1-3N0-2 treated with preoperative carboplatin and paclitaxel (NAC-group) and 53 NSCLC patients stage T1-4N0-1 treated with surgery without preceding chemotherapy (OP-group) served as controls. The diagnostic biopsies and subsequent resection samples were compared in order to evaluate for concordance in TS expression in groups with and without preoperative chemotherapy.

      Results
      No statistically significant change in TS expression was observed between diagnostic biopsies and subsequent surgical resections of primary tumors in either the OP-group (p=0.186) or the NAC-group (p=0.542). Primary tumors were discordant between diagnostic biopsies and resection specimens when TS expression was dichotomized into high (H-score>150) and low (H-score ≤150), in 45% and 33% in the OP-group and NAC-group, respectively (p=0. 288).

      Conclusion
      The discordance observed between paired serial samples likely reflects intratumoral heterogeneity of TS expression and highlights the need of sufficient representative material for TS expression analysis if this biomarker is to be used for treatment selection.. TS expression in primary tumors remained unchanged and new biopsies for deciding on 2nd line pemetrexed do not seem warranted based on the current results.

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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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      P3.06-021 - Changes in epidermal growth factor receptor expression during chemotherapy in non-small cell lung cancer (ID 1959)

      09:30 - 16:30  |  Author(s): J.N. Jakobsen

      • Abstract

      Background
      Antibodies targeting epidermal growth factor receptor (EGFR), such as cetuximab, may potentially improve outcome in non-small cell lung cancer (NSCLC) patients with high EGFR expression. The EGFR expression may be heterogeneously distributed within tumors and small biopsies may thus not accurately reveal the EGFR expression and EGFR expression may also change during chemotherapy.

      Methods
      EGFR expression in diagnostic biopsies and resection specimen was compared in 53 NSCLC patients stage T1-4N0-1M0 treated with surgery without preceding chemotherapy (OP-group) and from 65 NSCLC patients stage T1-3N0-2M0 (NAC-group) treated with preoperative carboplatin and paclitaxel were analyzed regarding EGFR expression to evaluate the concordance of EGFR expression between samples.

      Results
      No significant change in EGFR expression H-score was observed when comparing serial samples from either the OP-group (p=0.934) treated with surgery or the NAC-group (p=0.122) treated with preoperative chemotherapy. Discordance between tumors dichotomized according to EGFR expression (high: H-score≥200; low: H-score<200) in diagnostic biopsies and immediate resection specimens was 25% in the OP-group and 33% in the NAC-group (p=0.628).

      Conclusion
      EGFR expression in 25% of diagnostic biopsies may potentially not be accurate compared to the prevailing pattern in the whole tumor based on the larger resection specimens. This may potentially be an obstacle for proper use of antibodies targeting the EGFR in NSCLC. EGFR expression does however not change significantly during paclitaxel and carboplatin and rebiopsies in order to decide on anti-EGFR antibody therapy following chemotherapy does not seem warranted.