Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients

Lugli, Alessandro; Vlajnic, Tatjana; Giger, Olivier; Karamitopoulou, Eva; Patsouris, Efstratios S; Peros, George; Terracciano, Luigi M; Zlobec, Inti (2011). Intratumoral budding as a potential parameter of tumor progression in mismatch repair-proficient and mismatch repair-deficient colorectal cancer patients. Human pathology, 42(12), pp. 1833-40. Philadelphia, Pa.: Elsevier 10.1016/j.humpath.2011.02.010

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In colorectal cancer, tumor budding at the invasive front (peritumoral budding) is an established prognostic parameter and decreased in mismatch repair-deficient tumors. In contrast, the clinical relevance of tumor budding within the tumor center (intratumoral budding) is not yet known. The aim of the study was to determine the correlation of intratumoral budding with peritumoral budding and mismatch repair status and the prognostic impact of intratumoral budding using 2 independent patient cohorts. Following pancytokeratin staining of whole-tissue sections and multiple-punch tissue microarrays, 2 independent cohorts (group 1: n = 289; group 2: n = 222) with known mismatch repair status were investigated for intratumoral budding and peritumoral budding. In group 1, intratumoral budding was strongly correlated to peritumoral budding (r = 0.64; P < .001) and less frequent in mismatch repair-deficient versus mismatch repair-proficient cases (P = .177). Sensitivity and specificity for lymph node positivity were 72.7% and 72.1%. In mismatch repair-proficient cancers, high-grade intratumoral budding was associated with right-sided location (P = .024), advanced T stage (P = .001) and N stage pN (P < .001), vascular invasion (P = .041), infiltrating tumor margin (P = .003), and shorter survival time (P = .014). In mismatch repair-deficient cancers, high intratumoral budding was linked to higher tumor grade (P = .004), vascular invasion (P = .009), infiltrating tumor margin (P = .005), and more unfavorable survival time (P = .09). These associations were confirmed in group 2. High-grade intratumoral budding was a poor prognostic factor in univariate (P < .001) and multivariable analyses (P = .019) adjusting for T stage, N stage distant metastasis, and adjuvant therapy. These preliminary results on 511 patients show that intratumoral budding is an independent prognostic factor, supporting the future investigation of intratumoral budding in larger series of both preoperative and postoperative rectal and colon cancer specimens.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

UniBE Contributor:

Lugli, Alessandro; Giger, Olivier and Zlobec, Inti

ISSN:

0046-8177

Publisher:

Elsevier

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:17

Last Modified:

06 Dec 2013 13:25

Publisher DOI:

10.1016/j.humpath.2011.02.010

PubMed ID:

21664647

Web of Science ID:

000297445600002

URI:

https://boris.unibe.ch/id/eprint/5010 (FactScience: 209703)

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