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

Abstract

BackgroundSmall 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 MethodsThis 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.ResultsFrom 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).ConclusionEPNEC 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.

Study of the Possible Alleviated Role of Atorvastatin on Irinotecan‐Induced Lingual Mucosal Damage: Histological and Molecular Study

“…Ki-67 expression was low in the immunohistochemical and gene expression results as well. This coincides with the results reported by de M Rêgo et al [ 27 ] showing the antiproliferative role of CPT-11 that could explain the tongue's mucosal damage detected in this study. In the same context, a remarkable thickening of the keratin layer was observed, which was previously explained by the high sensitivity of taste buds to chemotherapy, taste bud damage, and the loss of sensory innervation which has been documented to have a role in disturbed keratinization and a loss of taste sensation [ 28 ].…”

The Ki-67 antigen in the new 2021 World Health Organization classification of lung neuroendocrine neoplasms

“…Ki-67 labeling index is recommended by the European Society of Neuroendocrine Tumors (ENETS) in the diagnostic evaluation/work-up guidelines of lung NETs 60 . There does not appear to be a meaningful role for the Ki-67 proliferative status in lung NECs to stratify patients for radiotherapy 62 , non-conventional chemotherapy in small tumor series 63 or first-line platinum-based chemotherapy for SCLC 64 .…”

Utility of KI-67 as a prognostic biomarker in pulmonary neuroendocrine neoplasms: a systematic review and meta-analysis

“…http://bmjopen.bmj.com/ BMJ Open: first published as 10.1136/bmjopen-2020-041961 on 3 March 2022. Downloaded fromOpen accessStudy characteristics and quality evaluationSeven papers, published between 2013 and 2018 including 1268 patients (693 TC, 281 AC, 94 LCNEC and 190 SCLC), fulfilled the inclusion criteria for metaanalysis [18][19][20][21][22][23][24]. All included studies were retrospective and observational in nature, with no prospective studies identified.…”