Prognostic significance of EGFR FISH and IHC in non small-cell lung cancer patients treated with chemotherapy alone

Abstract

7193 Background: High EGFR gene copy number by fluorescence in situ hybridization (FISH) predicts response and survival benefit in non small-cell lung cancer (NSCLC) patients (pts) treated with EGFR tyrosine-kinase inhibitors, but its prognostic value remains debated. We aimed to evaluate the association of EGFR FISH, EGFR immunohistochemistry (IHC) and prognosis in NSCLC pts treated with chemotherapy alone. Methods: 85 pts treated with platinum-containing chemotherapy (median follow up of 15 months [range: 2–29 months]) were included in the study. There were 47% females, 35% of pts with performance status (PS) 0, 53% PS = 1 and 12% PS = 2, 6% of never-smokers. Median age was 62 years (range: 41–80 years). Stage I-IIIA was diagnosed in 7%, stage IIIB - 44% and stage IV - 48% pts. Adenocarcinoma was the most common histology (51% pts). EGFR FISH was performed using LSI EGFR SpectrumOrange/CEP 7 SpectrumGreen probe and IHC using DAKO PharmDx kit. Results: FISH results were available in 79 pts (93%), and EGFR FISH-positive tumors (high polysomy or gene amplification) were found in 28 pts (35%). IHC results were available in 81 pts (95%) and 25 pts (31%) were scored as positive (staining index ≥200). Distribution of clinical characteristics did not differ according to either FISH or IHC result. FISH-positive pts had higher EGFR IHC staining indices as compared with FISH-negative pts (median 160 vs. 60, p = 0.005, Mann-Whitney U test). Median survival of FISH-positive pts was 12.6 months vs. 8.1 months in FISH-negative pts (log-rank p = 0.68; HR = 0.88 [95% CI: 0.49–1.59]) and the respective figures for progression-free survival (PFS) were 7.5 vs. 4.9 months, log-rank p = 0.72; HR = 0.91 [95% CI: 0.55–1.51]. Median survival in IHC-positive vs. IHC-negative pts was 6.6 months vs. 9.2 months (log-rank p = 0.44; HR = 1.27 [95% CI: 0.69–2.36]). There was no significant difference in PFS (median of 4.8 vs. 5.3 months, respectively; log-rank p = 0.71; HR = 1.11 [95% CI: 0.64–1.92]). FISH and IHC remained insignificant in a Cox regression survival analysis. Conclusion: In this cohort of NSCLC patients treated with chemotherapy alone, EGFR FISH was associated with EGFR IHC and both features had no statistically significant influence on prognosis. [Table: see text]