ecancermedicalscience

Clinical Study

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

11 Sep 2017
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

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.

Related Articles

Rogério Agenor de Araújo, Felipe Andrés Cordero da Luz, Eduarda da Costa Marinho, Camila Piqui Nascimento, Lara de Andrade Marques, Patrícia Ferreira Ribeiro Delfino, Rafael Mathias Antonioli, Breno Jeha Araújo, Ana Cristina Araújo Lemos da Silva, Maria Luiza Gonçalves dos Reis Monteiro, Morun Bernardino Neto, Marcelo José Barbosa Silva
Frederic Ivan Ting, Crizel Denise Uy, Katrina Gaelic Bebero, Danielle Benedict Sacdalan, Honey Sarita Abarquez, Grace Nilo, Buenaventura Ramos Jr, Dennis L Sacdalan, Arnold John Uson
Nicolas Panzardi, Matias Mihura-Irribarra, Daniela Speisky, Joaquin Fernandez-Alberti, Mariana Toffolo Pasquini, Pablo Dezanzo, Daniel Enrique Pirchi
João Glasberg, Aley Talans, Thomás Rivelli Giollo, Débora Zachello Recchimuzzi, João Evangelista Bezerra Neto, Rossana Veronica Mendonza Lopez, Paulo Marcelo Gehm Hoff, Rachel P Riechelmann
Yasmim Portela Machado de Aguiar, Adjanny Estela Santos de Souza, Christian Diniz Lima e Silva, Sândrea Ozane do Carmo Queiroz
Sofia Ali Syed, Muhammad Asif Qureshi, Saeed Khan, Rajesh Kumar, Yusra Shafique, Bilal Ahmed Khan, Jawad Safdar