Microsatellite instability in young patients with mucinous colorectal cancers - characterization using molecular testing, immunohistochemistry, and histological features

• Published in: Indian journal of cancer Vol. 56; no. 4; pp. 309 - 314
• Main Authors: Mathews, Nitty, Masih, Dipti, Mittal, Rohin, Perakath, Benjamin, Sakthi, Dhananjayan, Rebekah, Grace, Pai, Rekha, Pulimood, Anna
• Format: Journal Article
• Language: English
• Published: India Wolters Kluwer India Pvt. Ltd 01.10.2019; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt. Ltd
• Subjects: Adenocarcinoma, Mucinous - diagnosis; Adenocarcinoma, Mucinous - genetics; Adenocarcinoma, Mucinous - pathology; Adult; Biomarkers, Tumor - genetics; Cancer genetics; Cancer patients; Chemotherapy; Childhood cancer; Colorectal cancer; Colorectal Neoplasms - diagnosis; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Deoxyribonucleic acid; Diagnosis; DNA; DNA Mismatch Repair; DNA-Binding Proteins - metabolism; Female; Formaldehyde; Genes; Genetic aspects; Genetic Markers - genetics; Health aspects; Humans; Immunohistochemistry; Lymphocytes; Male; Medical prognosis; Microsatellite Instability; Microsatellite Repeats - genetics; Molecular diagnostic techniques; Mutation; MutL Protein Homolog 1 - metabolism; MutS Homolog 2 Protein - metabolism; Pathology, Molecular; Pediatric research; Physiological aspects; Proteins; Sample size; Studies; Thermal cycling; Tumors; Young Adult; India; United States > US; Germany; microsatellite instability; Carcinoma; colorectal cancer; histology; mucinous carcinoma; mismatch repair; immunohistochemistry
• ISSN: 0019-509X; 1998-4774
• DOI: 10.4103/ijc.IJC_224_18

CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers - BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects.