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Luisella Righi



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    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
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      P1.13-20 - MET Protein Expression and Activation During Targeted Therapy in EGFR Mutated Lung Adenocarcinoma (ID 13478)

      16:45 - 18:00  |  Author(s): Luisella Righi

      • Abstract
      • Slides

      Background

      In EGFR mutated (EGFRm) lung adenocarcinoma (ADC) the tyrosine kinase (TK) receptor MET is involved in acquired resistance to anti-EGFR treatment. We analyzed MET protein expression and activation in EGFRm lung ADC treated with TK inhibitors (TKI).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with advanced EGFRm lung ADC, treated at the Oncology Department - San Luigi Hospital, who underwent tissue biopsy for diagnosis and tissue re-biopsy at disease progression for T790M test (after a negative liquid biopsy) were selected. c-MET (clone SP44) and phosphorylated (p-) MET (Tyr1234/1235, D26) expression was analyzed by immunohistochemistry and evaluated as H-Score (HS).

      4c3880bb027f159e801041b1021e88e8 Result

      Tumor tissues from 18 advanced EGFRm patients (12 female and 6 male; mean age 59 years) were available. On April 2018, 10 patients were alive and 8 were died. 11/18 (61%) cases harbored a T790M point mutation (T790M+) detected at tissue re-biopsy.

      At the baseline tumor tissue, lower c-MET expression levels were found in T790M+ (mean HS value= 135, range 40-250) compared to the T790M negative (T790M-) group (mean HS value= 226, range 100-300) (p=0.02). Furthermore, in T790M+ patients p-MET was expressed in 2/11 cases (18%, HS values=5 and 60) while in the T790M- group p-MET was expressed in 3/7 (43%, HS values=5, 240 and 240) cases (although with no significant p value).

      After first line TKI treatment, in the T790M+ group c-MET expression (mean HS value=140, range 5-300) was augmented in 7 and reduced in 4 cases, while p-MET was positive in 2/11 cases (HS values of 300 and 30). No significant differences in survival were found.

      In the T790M- group the c-MET mean HS value was 152 (range 30-300) and the 4/7 cases with higher c-MET expression levels (HS> 152) had a significant shorter PFS (p=0.02, HR=0.3, median survival: 7.5 vs 24 months). Furthermore, in this group p-MET positivity was maintained in the same 3 cases (with HS values= 240, 180, 10) and the two patients with higher MET activation had short PFS (9 and 6 months) at first line TKI treatment.

      8eea62084ca7e541d918e823422bd82e Conclusion

      Our preliminary analyses suggest that a strong expression of basal c-MET receptor in advanced EGFRm ADC may predict a T790M negative status at disease progression. Furthermore MET higher expression and activation may play a role in acquired resistance to TKI, although a limited number of cases have been analyzed. Thereby, we propose to monitor MET status along treatment and to reconsider MET-directed therapies for a well-selected subset of EGFRm lung ADC patients.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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    P2.09 - Pathology (Not CME Accredited Session) (ID 958)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 16:45 - 18:00, Exhibit Hall
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      P2.09-21 - Women with Synchronous or Metachronous Lung and Ovarian Cancers: A Multi-Institutional Report (ID 12485)

      16:45 - 18:00  |  Author(s): Luisella Righi

      • Abstract
      • Slides

      Background

      In women, lung cancer (LC) and ovarian cancer (OC) are, respectively, the second and eighth malignancies for incidence in developed Countries. Despite increasing incidence and mortality of LC, association with OC is rare and no literature data are available on this topic yet. Our aim was to describe a series of patients with synchronous or metachronous LC and OC and to identify common clinical and pathological patterns.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      We retrieved the medical charts of patients who referred to 30 European Oncological Institutes from 2008 to 2018. When patients with synchronous (up to 3 months of time interval in onset) or metachronous LC and OC were found, we collected detailed medical history, pathological features and clinical outcomes. Whenever available, formalin fixed paraffin embedded tumor tissue from both specimens was collected for centralized pathology revision with an immunohistochemical marker panel including TTF-1 and PAX-8. In ambiguous cases, a broader panel was performed (p40, CK-7, WT1, CA125, Calretinin, EMA, CEA, CgA, Vimentin, Napsin-A). Whenever tested, genetic alterations in LC and OC were also reported.

      4c3880bb027f159e801041b1021e88e8 Result

      As of April 2018, among 30 European Oncological Centers (Italy, France, Slovenia), 11 retrieved in their series patients with a history of LC and OC, for a total of 18 cases in the last 10 years. Paired histological specimens were available in 6 cases. One patient was excluded, since pathology revision revealed that lung lesions were metastases from serous OC. Thus, analyses were performed on 17 patients. In 10/17 cases (58.8%), LC and OC were metachronous and, in 6/10 cases, OC preceded LC diagnosis, with a median interval of 4.5 years. Median age at diagnosis of the first malignancy was 62 years, the majority of patients (64.7%) were never-smoker, 6 had cancer familial history. Interestingly, 4 patients (23.5%) reported also a third or fourth malignancy. After a median follow-up of 6.5 years, 10 patients are alive. Regarding histology, most of LC were adenocarcinoma (14/17, 82.3%). Molecular status was available in 9/14 cases: 4 had EGFR mutation, 1 B-RAF mutation and 2 ALK translocation. OC were mostly high-grade serous (83,3%). BRCA status was available in 6 patients: 2 mutated, 2 wild-type and 2 affected by variants of unknown significance (USV). Moreover, one synchronous case presented both BRCA-USV and B-RAF mutation.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In our series, synchronous and metachronous LC and OC were often driven by genetic alterations. Further genetic analysis with next generation sequencing technology has already been planned.

      6f8b794f3246b0c1e1780bb4d4d5dc53

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