EP506 - The Molecular Landscape Of Colorectal Cancers In Northern Tanzania.

ePoster Presenter(s)

• 

  Alexander T. Hawkins, MD, MPH

  Associate Professor
  Vanderbilt University Medical Center
  Vanderbilt University Medical Center
  Nashville, TN, United States

  Disclosure information not submitted.

Author(s)

• BM

  Blandina T. Mmbaga, Prof

  Director KCRI
  Kilimanjaro Clinical Research Institute
  Moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• MS

  Martha J. Shrubsole, PhD

  Ingram Professor of Cancer Research
  Vanderbilt University Medical Center
  Nashville, Tennessee, United States

  Disclosure information not submitted.
• KL

  Ken Lau, PhD

  Professor
  Vanderbilt University
  Nashville, Tennessee, United States

  Disclosure information not submitted.
• KW

  Kay Washington, MD, PhD

  Professor of Pathology
  Vander
  Nash, Tennessee, United States

  Disclosure information not submitted.
• AM

  Alex Mremi, PhD

  Anatomic Pathologist
  Kilimanjaro Christian Medical Centre
  Moshi, Kilimanjaro, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• AP

  Angela Elisha Pallangyo, MMed in Anatomic Pathology

  Anatomic Pathologist
  KCMC University
  Moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• DM

  Daniel Eliamini Mbwambo, Histotech

  Laboratory scientist
  Kilimanjaro Christian Medical center
  Kilimanjaro, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• MM

  Modesta Paschal Mitao, Medical doctor

  Medical doctor, Master of science in Epidemiology and applied Biostatistics
  Kilimanjaro Clinical Research Institute
  Kilimanjaro, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• GL

  Godrule Praygod Lyimo, n/a

  Data analyst
  KILIMANJARO CLINICAL RESEARCH INSTITUTE (KCRI)
  Moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• HS

  Huruma Sapheli, n/a

  research Nurse and community advasory board Member
  Kilimanjaro Clinical Research Institute
  moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• FS

  Furaha M. Serventi, Fellow of the college of Radiation oncologists of south Africa

  Clinical and Radiation oncologist. Head of the KCMC cancer care centre. lecturer kCMC university
  Kilimanjaro Christian Medical center
  Moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• AM

  Athanasia Maro, Msc

  An experienced Molecular biologist focuses diagnostic techniques of Enteric , AFI and cancer
  KILIMANJARO CHRISTIAN MEDICAL CENTRE
  MOSHI, Kilimanjaro, Tanzania

  Disclosure information not submitted.
• RC

  Robert j. Coffey, Dr

  professor
  vumc
  Nashville, Tennessee, United States

  Disclosure information not submitted.

Senior Author(s)

• AH

  Ayesiga m. Herman, n/a

  Colorectal Surgeon
  Kilimanjaro Christian Medical Center
  Moshi, Kilimanjaro, Tanzania

  Disclosure information not submitted.

Purpose/Background: The incidence of colorectal cancer (CRC) is rising, particularly in low-and-middle income countries where a substantial proportion of patients are early onset CRC (EOCRC). Yet, the molecular landscape of CRC is still under-studied in Africa. A few molecular studies on the African continent have identified possible differences in the genetic landscape of CRC, with a high prevalence of microsatellite instability (MSI). However, only a small percentage of CRC patients are able to access these tests, essential in decision making for treatment modalities. In Tanzania, molecular testing of CRC specimens is not routine. With a focus on a typical referral hospital in a low-resource setting in East Africa, we embarked on a project to build capacity for conducting molecular testing for CRC. Our main aim was to 1) establish an audit of all cases retrospectively and describe the burden of CRC cases presenting to the hospital over a period of 8 years, including a subset for molecular profiling and 2) establish the feasibility for building a prospective registry that will form a basis for enhancing pathological and molecular testing of CRC for future cases.

Methods/Interventions: We retrospectively reviewed the cancer registry at Kilimanjaro Christian Medical Centre from 2017 to 2025, and abstracted clinical and pathological data for all cases. We selected 100 samples by age of onset and site of the cancer and used descriptive statistics to assess the demographic, clinical and pathological factors associated with molecular features. The archived FFPE blocks were used to assess the MMR protein status and other key biomarkers (BRAFV600E, Beta Catenin, and CD8) using IHC, and MSI rates were evaluated using PCR. At least 44 EOCRC and 50 late onset (LO) CRC samples were successfully assayed for at least one marker. Chi-squared test or Fisher's exact test (where applicable) were used to compare differences in categorical data. Survival probabilities in the groups defined by age of onset were computed using Kaplan Meier survival functions.

Results/Outcomes: Of the 554 CRC cases, 55% were male, 31% were early onset CRC (EOCRC), and 20% had a family history of CRC. Out of the samples assayed, 29/78 (37%) were microsatellite stable (MSS), 22/78 (28%) MSI-High, and 27/78 (35%) MSI-Low. In comparison to LOCRCs, EOCRCs were equally likely to be MSI-H (30% EOCRC vs 27% LOCRC). Of the MMR protein-deficient tumors, 40%, 49%, 11% and 37% of MLH1, MSH2, MSH6 and PSM2 categories respectively were deficient. 5% (4/88) of the samples had beta-catenin staining in nucleus, while 36% (32/88) had both nuclear and membranous staining. 50% of the MSI-H specimens had nuclear and membranous beta-catenin staining, and none had nuclear expression. Of the MSI-H tumors, 36% were CD8 positive. BRAFV600E mutation was seen in 8 samples (n=92) whereby 6 were of EOCRC and 2 were of LOCRC. Overall, 33% of patients were recorded as deceased, and additionally, over a quarter were lost to follow-up. Patients with late onset CRC had a higher hazard ratio of death compared to early onset CRC, HR 1.79 (95% CI 1.06, 3.03).

The Molecular Landscape Of Colorectal Cancers In Northern Tanzania.
Demographic and clinicopathologic characteristics of colorectal cancer cases
The Molecular Landscape Of Colorectal Cancers In Northern Tanzania.
Molecular profile of CRC patients