Clinical application of digital pathology in small intestinal neuroendocrine tumours: proposal of a new G0 category.
Small intestinal neuroendocrine tumours (siNETs) are usually indolent neoplasms, most of which are classified as grade 1 with very low proliferative activity. In practice, Ki-67 in G1 siNETs is often reported simply as '<3%', limiting prognostic discrimination. Digital pathology now enables reliable automated quantification of very low Ki-67 values. We investigated whether precise Ki-67 quantification could improve prognostic stratification in G1 siNETs.
We retrospectively included 63 consecutive patients who underwent surgery for a G1 siNET at Beaujon Hospital between 2001 and 2017. Ki-67 was quantified on primary tumours (PTs) and, when available, lymph node and liver metastases, using QuPath automated image analysis. Ki-67 was assessed in the highest-proliferation hotspot (0.4 mm2; >2,000 tumour cells; Ki-67max) and as the mean of five hotspots (Ki-67mean). The primary endpoint was recurrence-free survival (RFS).
Among 63 patients, 33 underwent curative-intent surgery (median age: 56 years; 69% male). Median tumour size was 20 mm. At surgery, 87% were node-positive and 67% had synchronous metastases. Median Ki-67max/Ki-67mean in PTs was 0.99%/0.71%. In localised disease, Ki-67max predicted RFS (AUROC = 0.84). Median follow-up was 60.2 months. Median RFS was 112 months in patients with Ki-67max ≥1%, whereas no recurrences occurred in those with Ki-67max <1% (P = 0.04). Ki-67mean provided no additional prognostic value.
Precise digital Ki-67 quantification refines prognostic stratification in G1 siNETs. Tumours with Ki-67 <1% may represent a biologically distinct 'G0' subgroup associated with extremely low recurrence risk after curative surgery.
We retrospectively included 63 consecutive patients who underwent surgery for a G1 siNET at Beaujon Hospital between 2001 and 2017. Ki-67 was quantified on primary tumours (PTs) and, when available, lymph node and liver metastases, using QuPath automated image analysis. Ki-67 was assessed in the highest-proliferation hotspot (0.4 mm2; >2,000 tumour cells; Ki-67max) and as the mean of five hotspots (Ki-67mean). The primary endpoint was recurrence-free survival (RFS).
Among 63 patients, 33 underwent curative-intent surgery (median age: 56 years; 69% male). Median tumour size was 20 mm. At surgery, 87% were node-positive and 67% had synchronous metastases. Median Ki-67max/Ki-67mean in PTs was 0.99%/0.71%. In localised disease, Ki-67max predicted RFS (AUROC = 0.84). Median follow-up was 60.2 months. Median RFS was 112 months in patients with Ki-67max ≥1%, whereas no recurrences occurred in those with Ki-67max <1% (P = 0.04). Ki-67mean provided no additional prognostic value.
Precise digital Ki-67 quantification refines prognostic stratification in G1 siNETs. Tumours with Ki-67 <1% may represent a biologically distinct 'G0' subgroup associated with extremely low recurrence risk after curative surgery.
Authors
Guedj Guedj, Cléry Cléry, Chassac Chassac, Colnot Colnot, Rebours Rebours, Cros Cros, de Mestier de Mestier, Couvelard Couvelard, Tihy Tihy
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