Microsatellite instability among individuals of Hispanic origin with colorectal cancer

Abstract

Background: Although the presence of microsatellite instability (MSI) in patients with colorectal cancer (CRC) may have implications for prognosis, therapy, and family counseling, to the authors' knowledge, the prevalence of MSI has not been well described among individuals of Hispanic origin with CRC residing in the United States.

Methods: A retrospective cohort study using a hospital-based tumor registry to identify individuals of Hispanic origin who were diagnosed with CRC was conducted. Clinical data and tumor samples were retrieved. Molecular analyses included testing for MSI using a panel of 5 mononucleotide markers (BAT25, BAT26, NR21, NR24, and NR27) in a pentaplex polymerase chain reaction assay, as well as immunohistochemistry for the mismatch repair (MMR) proteins mutL homolog (MLH) 1, mutS homolog (MSH) 2, MSH6, and postmeiotic segregation increased 2 (PMS2) 2 on representative tissue.

Results: A total of 111 individuals of Hispanic origin with CRC were identified. Approximately 41.4% were women, and the median age was 57 years (interquartile range [IQR], 47.1-63.5 years). Eleven patients (9.9%; 95% confidence interval [95% CI], 4.2%-15.6%) had MSI CRC, whereas 14 patients (12.6%; 95% CI, 7.3%-21.8%) had CRC with ≥1 MMR protein abnormality. Ten of 11 individuals with MSI had clinical or molecular characteristics suspicious for Lynch syndrome such as abnormal expression of MSH2 and/or MSH6 (n=7) or age<50 years at the time of diagnosis (n=7).

Conclusions: The prevalence of MSI CRC among Hispanic individuals may be similar to that of other races and ethnicities, but clinicopathological characteristics, including age at diagnosis and pattern of abnormal MMR protein expression, suggest that sporadic MSI CRC may be less common in individuals of Hispanic origin, and that much of the MSI observed in this situation may be attributable to Lynch syndrome. Further exploration of the causes of disparate presentations of CRC by ethnicity and race is warranted.

Figure 1. Study Flow

One-hundred sixty one patients of Hispanic origin, with a neoplasm of the colon or rectum diagnosed and/or treated at Parkland Memorial Hospital at any time between 1997 and 2007 were identified as described in Methods. Fifty patients were excluded from analysis, providing 111 patients with primary adenocarcinoma of the colon or rectum for study. The prevalence of MSI CRC in the cohort was 9.9%. Abbreviations: CRC, colorectal cancer; MSI, microsatellite unstable CRC; MSS, microsatellite stable CRC

Figure 2

Figure 2a. MMR protein expression by IHC of a subject with abnormal/absent expression of MLH1 and PMS2 proteins (lack of staining, top panels) consistent with mutation or silencing of one of these genes, with preservation of expression in the nuclei for MSH2 and MSH6 proteins (presence of staining, bottom panels) consistent with normal gene function. Abbreviations: MMR, mismatch repair protein; IHC, immunohistochemistry Figure 2b. MMR protein expression by IHC of a subject with abnormal/absent expression of MSH2 and MSH6 proteins (lack of staining, bottom panels) consistent with mutation or silencing of one of these genes, with preservation of expression in the nuclei for MLH1 and PMS2 proteins (presence of staining, top panel) consistent with normal gene function. Abbreviations: MMR, mismatch repair protein; IHC, immunohistochemistry

Figure 2

Figure 2a. MMR protein expression by IHC of a subject with abnormal/absent expression of MLH1 and PMS2 proteins (lack of staining, top panels) consistent with mutation or silencing of one of these genes, with preservation of expression in the nuclei for MSH2 and MSH6 proteins (presence of staining, bottom panels) consistent with normal gene function. Abbreviations: MMR, mismatch repair protein; IHC, immunohistochemistry Figure 2b. MMR protein expression by IHC of a subject with abnormal/absent expression of MSH2 and MSH6 proteins (lack of staining, bottom panels) consistent with mutation or silencing of one of these genes, with preservation of expression in the nuclei for MLH1 and PMS2 proteins (presence of staining, top panel) consistent with normal gene function. Abbreviations: MMR, mismatch repair protein; IHC, immunohistochemistry

Figure 3. Survival by MSI status

Survival was determined by annual review of medical records and contact of patients (or families) by Parkland Cancer Registry staff. A non-significant trend towards favorable survival among individuals with MSI CRC compared to those with MSS CRC was observed, p=0.11, log-rank test for equality of survivor functions. Abbreviations: MSS, microsatellite stable CRC, MSI, microsatellite unstable CRC.