Background: Pulmonary-NETs are classified in low-grade typical carcinoid (TC), intermediate-grade atypical carcinoid (AC), and high-grade large cell carcinoma (LCNEC) and small cell carcinoma (SCLC). However, the proportion of pulmonary-NETs with similar histology that behave quite differently is not negligible. Recent studies favour the use of the proliferation marker Ki67.
Aim: To evaluate the utility of Ki67 for predicting metastasis in a cohort of patients with lung-NETs from a single centre.
Methods: Retrospective analysis of pulmonary-NETs (20142016). Ki67 counting was performed by an experienced pathologist using a manual conventional method when a representative section of tumour was available. The patients were divided into the group with metastasis (M1) and without metastasis (M0).
Results: Seventy nine lung-NETs were identified. Ki-67 were available for 50 cases: 24 TCs, 9 ACs, 15 LCNEC and 2 SCLC. The median age was 71 years, 26 female. 31 patients underwent surgical resection. Median follow-up: 28 months for the M0-group and 33 months for the M1-group. Tumour size ranged from 0.6 to 7.5 cm; mitoses ranged from 0 to 75. Twenty-six/50 developed metastases, most commonly in mediastinal lymph nodes and liver. Lymphovascular invasion was identified in 9. Twelve patients died due to disease progression. The mean Ki67 was 4.7% (±8.4S.D.) for TC, 13.8% (±8.4S.D.) for AC, 67% (±19.9S.D.) for LCNEC and 60% for the two SCLC (25 and 95%, respectively). The mean Ki-67 was significantly higher for AC compared with the TC group (P=0.01) and for pulmonary neuroendocrine carcinomas (LCNEC and SCLC) versus well-differentiated carcinoids (65.6±23.7S.D. vs 7.2±9.2S.D.; P=0.000). Ki67 was significantly higher in the M1-group (37.9%±32.6S.D. vs 15.3%±27.2S.D.; P=0.011). No statistically significant differences were found between the M0 and M1 groups regarding age, age at diagnosis, tumour size or mitotic count.
Conclusions: The Ki67-index showed higher values in AC compared to TC and in patients with metastases. This study suggests that analysis of Ki67-index may be a useful adjunctive measure for predicting metastasis and therefore for initiating early adjuvant multimodal therapy in pulmonary-NETs.
04 Dec 2017
UK and Ireland Neuroendocrine Tumour Society