Influence of microsatellite instability and KRAS and BRAF mutations on lymph node harvest in stage I–III colon cancers

Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I–III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni- and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5–5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2–4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored.publishedVersio

Agrárgazdasági Figyelő = Agricultural Economics Monitor

Gazdasági folyamatok és statisztikai eredmények Az Agrárgazdasági Kutató Intézet "Agrárgazdasági Figyelő" címmel negyedévenként áttekinti a főbb gazdasági folyamatokat és statisztikai eredményeket. A periodika négy állandó területre fokuszál: Az elmúlt negyedévben megjelent információk. Mi történt az agrárgazdaságban? Az AKI kiadványainak fontosabb megállapításai. Az agrárgazdaságot jellemző adatok ("statisztikai zsebkönyv"). Gyakran feltett kérdések (Esetenként szerepeltetjük azokat az alapkérdéseket, amelyek igénylik a közszereplők és érdeklődők tájékoztatását

Influence of microsatellite instability and KRAS and BRAF mutations on lymph node harvest in stage I–III colon cancers

Lymph node (LN) harvest is influenced by several factors, including tumor genetics. Microsatellite instability (MSI) is associated with improved node harvest, but the association to other genetic factors is largely unknown. Research methods included a prospective series of stage I–III colon cancer patients undergoing ex vivo sentinel-node sampling. The presence of MSI, KRAS mutations in codons 12 and 13, and BRAF V600E mutations was analyzed. Uni- and multivariate regression models for node sampling were adjusted for clinical, pathological and molecular features. Of 204 patients, 67% had an adequate harvest (≥12 nodes). Adequate harvest was highest in patients whose tumors exhibited MSI (79%; odds ratio [OR] 2.5, 95% confidence interval [CI] 1.2–4.9; P = 0.007) or were located in the proximal colon (73%; 2.8, 1.5–5.3; P = 0.002). In multiple linear regression, MSI was a significant predictor of the total LN count (P = 0.02). Total node count was highest for cancers with MSI and no KRAS/BRAF mutations. The independent association between MSI and a high LN count persisted for stage I and II cancers (P = 0.04). Tumor location in the proximal colon was the only significant predictor of an adequate LN harvest (adjusted OR 2.4, 95% CI 1.2–4.9; P = 0.01). An increase in the total number of nodes harvested was not associated with an increase in nodal metastasis. In conclusion, number of nodes harvested is highest for cancers of the proximal colon and with MSI. The nodal harvest associated with MSI is influenced by BRAF and KRAS genotypes, even for cancers of proximal location. Mechanisms behind the molecular diversity and node yield should be further explored

Whole-transcriptome sequencing identifies novel IRF2BP2-CDX1 fusion gene brought about by translocation t(1;5)(q42;q32) in mesenchymal chondrosarcoma.

Mesenchymal chondrosarcomas (MCs) account for 3-10% of primary chondrosarcomas. The cytogenetic literature includes only ten such tumours with karyotypic information and no specific aberrations have been identified. Using a purely molecular genetic approach a HEY1-NCOA2 fusion gene was recently detected in 10 of 15 investigated MCs. The fusion probably arises through intrachromosomal rearrangement of chromosome arm 8 q. We report a new case of MC showing a t(1;5)(q42;q32) as the sole karyotypic aberration. Through FISH and whole transcriptome sequencing analysis we found a novel fusion between the IRF2BP2 gene and the transcription factor CDX1 gene arising from the translocation. The IRF2BP2-CDX1 has not formerly been described in human neoplasia. In our hospital's archives three more cases of MC were found, and we examined them looking for the supposedly more common HEY1-NCOA2 fusion, finding it in all three tumours but not in the case showing t(1;5) and IRF2BP2-CDX1 gene fusion. This demonstrates that genetic heterogeneity exists in mesenchymal chondrosarcoma

Additional file 1: Figure S1. of Prognostic relevance of an epigenetic biomarker panel in sentinel lymph nodes from colon cancer patients

Venn diagram illustrating the overlap between HES-positive and DNA methylation biomarker-positive lymph nodes. (A) Individual lymph node level. (B) Patient level. Abbreviation: HES, hematoxylin-erythrosin-safranin. (PDF 146 kb

Histological images of the four MCs and characteristics of the <i>HEY1-NCOA2</i> fusion.

<p>(A) The typical biphasic histological pattern is observed in all tumours. (B) The <i>HEY1-NCOA2</i> fusion was detected using primers HEY1_F1 and NCOA2_E13-R3 in patients 2–4 but not in patient 1 whose tumour showed the t(1;5). (C) The <i>HEY1-NCOA2</i> fusion was confirmed by sequencing. The breakpoint positions were identical to those previously reported.</p