Small-bowel NETs: consider Ki67 on the largest mesenteric deposit

Design

Retrospective single-institution cohort

Population

75 jejunoileal well-differentiated NETs with nodal metastases or mesenteric deposits

Primary outcome

Progression and disease-specific death by Ki67 site

Effect

Deposit Ki67 HR 1.22 per 1% (95% CI 1.02 to 1.46); primary and nodal Ki67 not associated

A study in Histopathology (published 15 September) analysed 75 jejunoileal well-differentiated neuroendocrine tumours with nodal metastases or mesenteric tumour deposits. For each case the largest primary, largest node and largest deposit were stained for Ki67, and hotspot indices were measured by trained image analysis, validated against manual counts.

In 68% of cases a node or deposit had a higher Ki67 than the primary. Over a median follow-up of 72 months, 28% recurred. On multivariable analysis, Ki67 in the largest tumour deposit was the only index associated with progression (HR 1.22 per 1% increase, 95% CI 1.02 to 1.46). Primary and nodal Ki67, the highest index in the case, and the index of the largest focus were not. Deposit size, not any Ki67, was linked to disease-specific death.

Many laboratories grade on the primary because it is the obvious block. These findings suggest that, where a mesenteric deposit is present, staining it as well gives the more prognostic index. It is one retrospective series with few deaths, so it supports adding a deposit block rather than abandoning grading on the primary.

• Where a mesenteric tumour deposit is present in a jejunoileal NET, consider staining the largest deposit for Ki67.
• Report the Ki67 index from each site tested and state which block it came from.
• Record the size of the largest mesenteric deposit, which was associated with disease-specific death.
• Expect nodes or deposits to show a higher Ki67 than the primary in most cases.
• Use hotspot counting, by image analysis or manually, consistent with your validated method.

Why it matters

Grading on the primary alone may understate the proliferative activity that predicts progression.

Don't overread it

This is a single retrospective series of 75 cases; no grading guideline has yet changed.

The statistics, in plain English

A hazard ratio of 1.22 per 1% means each one-point rise in deposit Ki67 was linked to about 22% higher risk of progression. The interval starts just above 1 (1.02), so the effect is real in this cohort but its size is uncertain. With only six disease deaths, survival analyses have little power.

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