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Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

2565 - Microsatellite instability is associated with distinct clinical and molecular characteristics in early colon cancer: Analysis of a molecular registry of the AIO colorectal study group - Colopredict Plus

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Topics

Targeted Therapy;  Pathology/Molecular Biology

Tumour Site

Colon and Rectal Cancer

Presenters

Anke Reinacher-Schick

Citation

Annals of Oncology (2018) 29 (suppl_8): viii150-viii204. 10.1093/annonc/mdy281

Authors

A. Reinacher-Schick1, H. Juette2, S. Noepel-Duennebacke1, D. Arnold3, N. Basara4, H. Boehner5, T. Dahm1, I. Feder2, T. Herzog6, W. Hiller7, L. Mueller8, L. Engel9, M. Senkal10, C. Teschendorf11, G. Trenn12, B. Verdoodt2, H. Wolters13, W. Uhl14, A. Tannapfel2

Author affiliations

  • 1 Department Of Hematology, Oncology And Palliative Care, St. Josef-hospital Bochum, Ruhr-University Bochum, 44791 - Bochum/DE
  • 2 Institute Of Pathology, Ruhr-University Bochum, 44789 - Bochum/DE
  • 3 Hematology, Internal Medicine And Palliative Care, Asklepios Klinik Altona, 22763 - Hamburg/DE
  • 4 Hematology / Oncology / Internal Medicine, St. Franziskus Hospital Malteserkrankenhaus, 24939 - Flensburg/DE
  • 5 Surgical Clinic, Katholisches Krankenhaus Dortmund West, 44379 - Dortmund/DE
  • 6 General And Visceral Surgery, Katholisches Klinikum Bochum - St. Josef-Hospital, 44791 - Bochum/DE
  • 7 General, Visceral And Thoracic Surgery, Klinikum Lippe GmbH, 32756 - Detmold/DE
  • 8 Onkologie Unterems Leer Emden Papenburg, Onkologische Schwerpunktpraxis Leer-Emden, 26789 - Leer/DE
  • 9 Intestinal Centre, Klinikum Nürnberg Nord, 90419 - Nürnberg/DE
  • 10 General And Visceral Surgery, Marien Hospital Witten, 58452 - Witten/DE
  • 11 Internal Medicine, Katholisches Krankenhaus Dortmund West, 44379 - Dortmund/DE
  • 12 Internal Medicine / Hemato-oncology, Knappschaftskrankenhaus Bottrop Medizinische Klinik, 46242 - Bottrop/DE
  • 13 General And Visceral Surgery, St.-Josefs-Hospital Dortmund-Hoerde, 44263 - Dortmund/DE
  • 14 Department Of Surgery, St. Josef-hospital, Ruhr-University Bochum, 44791 - Bochum/DE

Resources

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Abstract 2565

Background

High microsatellite instability (MSI-H) is a prognostic marker in early colon cancer (CC) identified in retrospective analysis of many trials. However, broad validation in real-life cohorts and its association with clinical and molecular markers is lacking.

Methods

In Sep 2013 the molecular registry trial Colopredict Plus was intiatied in 70 German community cancer centers recruiting patients with UICC stage II and III CC. MSI was tested by immunohistochemistry (IHC) of mismatch repair proteins MLH1, MSH2, MSH6 and PMS2. In case of any loss of protein expression fragment length analysis (FLA) was performed, defining MSI high tumors (MSI-H) and MS stable tumors (MSS). Moreover, mutations in known prognostic factors in CC such as RAS, BRAF, PI3K and others were determined by next generation sequencing (NGS).

Results

By April 2018, 2102 patients have been recruited: median age 72 yrs., stage II/III: 1108/994 pts. So far, tissue was analysed in 1342 pts. Of these, 377 pts. were IHC neg with 290 pts. subsequently tested MSI-H upon FLA (21.6%). Median age was 73 yrs. female/male: 677/665 pts., stage II/III: 736/606 pts. Association of MS status with clinical and molecular factors is shown in the table. Upon NGS analysis we found 18.9% BRAF mutations, 41.5% KRAS mutations, 3.2% NRAS mutations and 25.1% PI3K mutations. MSI-H status was significantly associated with BRAF mutation and wildtype status of RAS.

Conclusions

MSI-H was more frequent in this community based registry compared to randomised trials, possibly related to a higher median age in our cohort. MSI-H was associated with female sex, right-sided primary tumor and BRAF mutations representing a heterogeneous subgroup of CC. First survival data will be presented at the meeting. Table: Association of clinical features with MSI-H in patients with CC (MS status determined by FLA).Table: 519P

AllMSI-H (%)MSS (%)
1342290 (21,6)1052 (78,4)
Median age737673
Male67778 (11,5)599 (88,5)
Female665212 (31,9)453 (68,1)
Stage II736181 (24,6)555 (75,4)
Stage III606109 (18)497 (82)
Right Colon793242 (30,5)551 (69,5)
Left Colon53647 (8,8)489 (91,2)

Clinical trial identification

DRKS Registry number: DRKS00004305 Release Date: 09-JAN-2013.

Legal entity responsible for the study

Ruhr-University Bochum, Institute of Pathology; Department of Hematology, Oncology and Palliative Care, St. Josef-Hospital.

Funding

State of North-Rhine Westfalia, Roche Pharma GmbH.

Editorial Acknowledgement

Not applicable

Disclosure

A. Reinacher-Schick: Honoria: Amgen, Roche, Pfizer, Sanofi-Aventis, Merck-Serono, Shire, Calgene, Lilly, BMS; Advisory board member: Amgen, Roche, Pfizer, Sanofi-Aventis, Celgene, Lilly, BMS, Merck-Serono; Studies sponsored by: Roche, Sanofi-Aventis, Calgene, Ipsen. H. Juette: Honoria: Roche, MSD, BMS, AstraZeneca, Amgen. S. Noepel-Duennebacke: Advisory board member: Bexalta, BMS; Studies sponsored by: Roche, Sanofi-Aventis, Celgene, Ipsen. D. Arnold: Honoraria: Bayer, Biocompatibles, Lilly, Merck, MSD, Roche, Sanofi, Servier, Sirtex; Advisory board member: Bayer, Lilly, Merck, Roche, Sanofi, Servier, Sirtex, Termuno; Studies sponsored by: Mologen, Roche, Sanofi. C. Teschendorf: Advisory board member: Roche. A. Tannapfel: Honoraria: Amgen, Roche, Pfizer, Merck-Serono, Celgene, BMS; Advisory board member: Amgen, Roche, Pfizer, Sanofi-Aventis, Celgene, BMS, Merck-Serono; Studies sponsored by: Roche, Celgene, Ipsen. All other authors have declared no conflicts of interest.

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