Expression of ERCC1, Bcl-2, Lin28a, and Ki-67 as biomarkers of response to first-line platinum-based chemotherapy in patients with high-grade extrapulmonary neuroendocrine carcinomas or small cell lung cancer

Juliana Florinda de M Rêgo, Raphael Salles Scortegagna de Medeiros, Maria Ignez Braghiroli, Breno Galvão, João Evangelista Bezerra Neto, Rodrigo Ramella Munhoz, Juliana Guerra, Suely Nonogaki, Lidia Kimura, Tulio Eduardo Pfiffer, Gilberto de Castro Jr, Paulo Marcelo Hoff, Duilio Rocha Filho, Frederico Perego Costa, Rachel P Riechelmann, Juliana Florinda de M Rêgo, Raphael Salles Scortegagna de Medeiros, Maria Ignez Braghiroli, Breno Galvão, João Evangelista Bezerra Neto, Rodrigo Ramella Munhoz, Juliana Guerra, Suely Nonogaki, Lidia Kimura, Tulio Eduardo Pfiffer, Gilberto de Castro Jr, Paulo Marcelo Hoff, Duilio Rocha Filho, Frederico Perego Costa, Rachel P Riechelmann

Abstract

Background: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities.

Materials and methods: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1.

Results: From July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02).

Conclusion: EPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.

Keywords: biomarkers; extrapulmonary neuroendocrine carcinoma; small cell lung cancer.

Figures

Figure 1.. Kaplan-Meier curves of OS for…
Figure 1.. Kaplan-Meier curves of OS for EPNEC versus SCLC.
Figure 2.. Kaplan-Meier curves of OS of…
Figure 2.. Kaplan-Meier curves of OS of 56 patients with EPNEC according to IHC expression (high expression: H-score ≥200) Bcl-2 (A), ERCC1 (B), Lin28a (C), and Ki-67 (D). Difference between the curves was evaluated by the log-rank test.
Figure 3.. Kaplan-Meier curves of OS of…
Figure 3.. Kaplan-Meier curves of OS of 76 patients with SCLC according to IHC expression (high expression: H-score ≥ 200) Bcl-2 (A), ERCC1 (B), Lin28a (C) and Ki-67 (D). Difference between the curves was evaluated by the log-rank test.
Figure 4.. Kaplan-Meier curves of OS of…
Figure 4.. Kaplan-Meier curves of OS of 56 patients with EPNEC available to survival analysis according to the degree of differentiation (well differentiated and poorly differentiated). The difference between the curves was evaluated by the log-rank method.

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