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. 2014 Feb 18;110(4):1008-13.
doi: 10.1038/bjc.2013.797. Epub 2013 Dec 24.

Intratumoural budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastases in colon and rectal cancer patients

I Zlobec  1 , M Hädrich  2 , H Dawson  3 , V H Koelzer  3 , M Borner  4 , M Mallaev  5 , B Schnüriger  2 , D Inderbitzin  2 , A Lugli  3
Affiliations

Intratumoural budding (ITB) in preoperative biopsies predicts the presence of lymph node and distant metastases in colon and rectal cancer patients

I Zlobec et al. Br J Cancer. .

Abstract

Background: In colorectal cancer (CRC), tumour budding at the invasion front is associated with lymph node (LN) and distant metastasis. Interestingly, tumour budding can also be detected in biopsies (intratumoural budding; ITB) and may have similar clinical importance. Here we investigate whether ITB in preoperative CRC biopsies can be translated into daily diagnostic practice.

Methods: Preoperative biopsies from 133 CRC patients (no neoadjuvant therapy) underwent immunohistochemistry for pan-cytokeratin marker AE1/AE3. Across all biopsies for each patient, the densest region of buds at × 40 (high-power field; HPF) was identified and buds were counted.

Results: A greater number of tumour buds in the biopsy was associated with pT stage (P=0.0143), LN metastasis (P=0.0007), lymphatic (P=0.0065) and venous vessel invasion (P=0.0318) and distant metastasis (cM1) (P=0.0013). Using logistic regression, a 'scale' was developed to estimate the probability of LN and distant metastasis using the number of tumour buds (e.g. 10 buds per HPF: 64% chance of LN metastasis; 30 buds per HPF: 86% chance). Inter-observer agreement for ITB was excellent (intraclass correlation coefficient: 0.813).

Conclusion: Tumour budding can be assessed in the preoperative biopsy of CRC patients. It is practical, reproducible and predictive of LN and distant metastasis. Intratumoural budding qualifies for further investigation in the prospective setting.

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Figures

Figure 1
Figure 1
Assessment of intratumoural budding. Preoperative colonic biopsy stained for pan-cytokeratin (brown) to highlight single tumour buds. The densest area (hot-spot) of intratumoural budding is identified. At × 40 magnification, the total number of tumour buds in one single HPF is counted. The full colour version of this figure is available at British Journal of Cancer online.
Figure 2
Figure 2
Study design. Out of an initial cohort of 346 patients, matched preoperative biopsies were available for 185. Cases were re-reviewed. Patients receiving preoperative therapy were further excluded. Biopsies underwent immunohistochemistry and the final number of evaluable cases was 133.
Figure 3
Figure 3
Probability scale. The greater the number of buds is, the greater the risk of metastasis.
See this image and copyright information in PMC

References

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