Sporadic colon cancer

Mismatch repair immunohistochemistry and microsatellite instability in Omani subjects

Hassan Ashktorab, Hassan Brim, Marwa Al-Riyami, Anand Date, Kamla Al-Mawaly, Masoud Kashoub, Rayhaneh Al-Mjeni, Duane T. Smoot, Mansoor Al-Moundhri, Suleiman Al-Hashemi, Shyam S. Ganguly, Sandy Raeburn

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Background: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the world, and there are suggestions of a particularly high incidence in the Middle East, including those of African origin. Defects in DNA mismatch repair (MMR) systems are involved in the carcinogenesis of both sporadic and inherited human cancers. We assessed colonic cancers in an attempt to identify tumors with DNA MMR deficiency and microsatellite instability (MSI). Additionally, we tested the ability of cell cycle regulator p16 that effects cell proliferation and can be abrogated by hypermethylation of the promoter region. Methods: We reviewed the charts of 756 patients who were referred to the Oman major colonoscopy unit of the Sultan Qaboos University Hospital and Royal Hospital from the years 2000 to 2004. Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L. The expression status of MMR genes and MSI was correlated with cancer stage, location, and histology. A total of 49 tumors were analyzed for histopathology, MSI, and hMLH1/hMSH2 protein expression analysis. The methylation status of the p16 promoter was determined by methylation-specific polymerase chain reaction (PCR). Results: The mean age for the carcinomas was 52.2 years and 53% of the patients were male. The majority of the tumors were left-sided. The information currently available indicates that there is an incidence of 4.7% colon cancer (49/1036) and 12.1% (126/1290) colon adenoma among the cases who underwent colonoscopy at these centers. The rate of MSI-H was 12.2% (n = 6), which appears to be the same as previously reported in literature. Eight of 49 tumors (16.3%) were MMR defective by IHC. Defects in the mismatch repair genes hMLH1 and hMSH2 were found in four (66.7%) and two (33.3%) of CRCs MSI-H cases, respectively. Defects in hMLH1 expression in tumors were commonly associated with moderate differentiation. The p16 promoter was methylated in 4% of tumors. Conclusion: This is the first genetic study of CRC in this region of the world to demonstrate the incidence of MSI, p16 methylation, and hMLH1 and MSH2 expression in the Omani population. In addition, a relatively high frequency of CRC in younger age groups was noted, which is an important observation. The left-sided preponderance of MMR defective tumors was mostly associated with hMLH1, and with possible loss of hMSH2 expression, an observation that differs from studies on other populations. In conclusion, although the overall rate of CRC is unknown in this region, the frequency of MSI in CRC in this region appears to be the same as in Caucasians in the USA.

Original languageEnglish
Pages (from-to)2723-2731
Number of pages9
JournalDigestive Diseases and Sciences
Volume53
Issue number10
DOIs
Publication statusPublished - Oct 2008

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Microsatellite Instability
DNA Mismatch Repair
Colonic Neoplasms
Immunohistochemistry
Colorectal Neoplasms
Neoplasms
Methylation
Colonoscopy
Incidence
Observation
DNA Repair-Deficiency Disorders
Oman
Middle East
Genetic Promoter Regions
Adenoma
Microsatellite Repeats
Population
Genes
Histology
Cell Cycle

Keywords

  • CRC
  • MSI
  • MSP
  • Oman
  • p16

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Sporadic colon cancer : Mismatch repair immunohistochemistry and microsatellite instability in Omani subjects. / Ashktorab, Hassan; Brim, Hassan; Al-Riyami, Marwa; Date, Anand; Al-Mawaly, Kamla; Kashoub, Masoud; Al-Mjeni, Rayhaneh; Smoot, Duane T.; Al-Moundhri, Mansoor; Al-Hashemi, Suleiman; Ganguly, Shyam S.; Raeburn, Sandy.

In: Digestive Diseases and Sciences, Vol. 53, No. 10, 10.2008, p. 2723-2731.

Research output: Contribution to journalArticle

Ashktorab, H, Brim, H, Al-Riyami, M, Date, A, Al-Mawaly, K, Kashoub, M, Al-Mjeni, R, Smoot, DT, Al-Moundhri, M, Al-Hashemi, S, Ganguly, SS & Raeburn, S 2008, 'Sporadic colon cancer: Mismatch repair immunohistochemistry and microsatellite instability in Omani subjects', Digestive Diseases and Sciences, vol. 53, no. 10, pp. 2723-2731. https://doi.org/10.1007/s10620-007-0189-3
Ashktorab, Hassan ; Brim, Hassan ; Al-Riyami, Marwa ; Date, Anand ; Al-Mawaly, Kamla ; Kashoub, Masoud ; Al-Mjeni, Rayhaneh ; Smoot, Duane T. ; Al-Moundhri, Mansoor ; Al-Hashemi, Suleiman ; Ganguly, Shyam S. ; Raeburn, Sandy. / Sporadic colon cancer : Mismatch repair immunohistochemistry and microsatellite instability in Omani subjects. In: Digestive Diseases and Sciences. 2008 ; Vol. 53, No. 10. pp. 2723-2731.
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abstract = "Background: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the world, and there are suggestions of a particularly high incidence in the Middle East, including those of African origin. Defects in DNA mismatch repair (MMR) systems are involved in the carcinogenesis of both sporadic and inherited human cancers. We assessed colonic cancers in an attempt to identify tumors with DNA MMR deficiency and microsatellite instability (MSI). Additionally, we tested the ability of cell cycle regulator p16 that effects cell proliferation and can be abrogated by hypermethylation of the promoter region. Methods: We reviewed the charts of 756 patients who were referred to the Oman major colonoscopy unit of the Sultan Qaboos University Hospital and Royal Hospital from the years 2000 to 2004. Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L. The expression status of MMR genes and MSI was correlated with cancer stage, location, and histology. A total of 49 tumors were analyzed for histopathology, MSI, and hMLH1/hMSH2 protein expression analysis. The methylation status of the p16 promoter was determined by methylation-specific polymerase chain reaction (PCR). Results: The mean age for the carcinomas was 52.2 years and 53{\%} of the patients were male. The majority of the tumors were left-sided. The information currently available indicates that there is an incidence of 4.7{\%} colon cancer (49/1036) and 12.1{\%} (126/1290) colon adenoma among the cases who underwent colonoscopy at these centers. The rate of MSI-H was 12.2{\%} (n = 6), which appears to be the same as previously reported in literature. Eight of 49 tumors (16.3{\%}) were MMR defective by IHC. Defects in the mismatch repair genes hMLH1 and hMSH2 were found in four (66.7{\%}) and two (33.3{\%}) of CRCs MSI-H cases, respectively. Defects in hMLH1 expression in tumors were commonly associated with moderate differentiation. The p16 promoter was methylated in 4{\%} of tumors. Conclusion: This is the first genetic study of CRC in this region of the world to demonstrate the incidence of MSI, p16 methylation, and hMLH1 and MSH2 expression in the Omani population. In addition, a relatively high frequency of CRC in younger age groups was noted, which is an important observation. The left-sided preponderance of MMR defective tumors was mostly associated with hMLH1, and with possible loss of hMSH2 expression, an observation that differs from studies on other populations. In conclusion, although the overall rate of CRC is unknown in this region, the frequency of MSI in CRC in this region appears to be the same as in Caucasians in the USA.",
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TY - JOUR

T1 - Sporadic colon cancer

T2 - Mismatch repair immunohistochemistry and microsatellite instability in Omani subjects

AU - Ashktorab, Hassan

AU - Brim, Hassan

AU - Al-Riyami, Marwa

AU - Date, Anand

AU - Al-Mawaly, Kamla

AU - Kashoub, Masoud

AU - Al-Mjeni, Rayhaneh

AU - Smoot, Duane T.

AU - Al-Moundhri, Mansoor

AU - Al-Hashemi, Suleiman

AU - Ganguly, Shyam S.

AU - Raeburn, Sandy

PY - 2008/10

Y1 - 2008/10

N2 - Background: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the world, and there are suggestions of a particularly high incidence in the Middle East, including those of African origin. Defects in DNA mismatch repair (MMR) systems are involved in the carcinogenesis of both sporadic and inherited human cancers. We assessed colonic cancers in an attempt to identify tumors with DNA MMR deficiency and microsatellite instability (MSI). Additionally, we tested the ability of cell cycle regulator p16 that effects cell proliferation and can be abrogated by hypermethylation of the promoter region. Methods: We reviewed the charts of 756 patients who were referred to the Oman major colonoscopy unit of the Sultan Qaboos University Hospital and Royal Hospital from the years 2000 to 2004. Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L. The expression status of MMR genes and MSI was correlated with cancer stage, location, and histology. A total of 49 tumors were analyzed for histopathology, MSI, and hMLH1/hMSH2 protein expression analysis. The methylation status of the p16 promoter was determined by methylation-specific polymerase chain reaction (PCR). Results: The mean age for the carcinomas was 52.2 years and 53% of the patients were male. The majority of the tumors were left-sided. The information currently available indicates that there is an incidence of 4.7% colon cancer (49/1036) and 12.1% (126/1290) colon adenoma among the cases who underwent colonoscopy at these centers. The rate of MSI-H was 12.2% (n = 6), which appears to be the same as previously reported in literature. Eight of 49 tumors (16.3%) were MMR defective by IHC. Defects in the mismatch repair genes hMLH1 and hMSH2 were found in four (66.7%) and two (33.3%) of CRCs MSI-H cases, respectively. Defects in hMLH1 expression in tumors were commonly associated with moderate differentiation. The p16 promoter was methylated in 4% of tumors. Conclusion: This is the first genetic study of CRC in this region of the world to demonstrate the incidence of MSI, p16 methylation, and hMLH1 and MSH2 expression in the Omani population. In addition, a relatively high frequency of CRC in younger age groups was noted, which is an important observation. The left-sided preponderance of MMR defective tumors was mostly associated with hMLH1, and with possible loss of hMSH2 expression, an observation that differs from studies on other populations. In conclusion, although the overall rate of CRC is unknown in this region, the frequency of MSI in CRC in this region appears to be the same as in Caucasians in the USA.

AB - Background: Colorectal carcinoma (CRC) is the most common gastrointestinal malignancy in the world, and there are suggestions of a particularly high incidence in the Middle East, including those of African origin. Defects in DNA mismatch repair (MMR) systems are involved in the carcinogenesis of both sporadic and inherited human cancers. We assessed colonic cancers in an attempt to identify tumors with DNA MMR deficiency and microsatellite instability (MSI). Additionally, we tested the ability of cell cycle regulator p16 that effects cell proliferation and can be abrogated by hypermethylation of the promoter region. Methods: We reviewed the charts of 756 patients who were referred to the Oman major colonoscopy unit of the Sultan Qaboos University Hospital and Royal Hospital from the years 2000 to 2004. Colon cancer tissue was assayed using immunohistochemistry for expression of hMLH1 and hMSH2, and a panel of five pairs of microsatellite primers (NR21, NR22, NR24, BAT25, and BAT26) for MSI-H analysis and additional dinucleotide markers (D17S250, D5S346, and D2S123) used for MSI-L. The expression status of MMR genes and MSI was correlated with cancer stage, location, and histology. A total of 49 tumors were analyzed for histopathology, MSI, and hMLH1/hMSH2 protein expression analysis. The methylation status of the p16 promoter was determined by methylation-specific polymerase chain reaction (PCR). Results: The mean age for the carcinomas was 52.2 years and 53% of the patients were male. The majority of the tumors were left-sided. The information currently available indicates that there is an incidence of 4.7% colon cancer (49/1036) and 12.1% (126/1290) colon adenoma among the cases who underwent colonoscopy at these centers. The rate of MSI-H was 12.2% (n = 6), which appears to be the same as previously reported in literature. Eight of 49 tumors (16.3%) were MMR defective by IHC. Defects in the mismatch repair genes hMLH1 and hMSH2 were found in four (66.7%) and two (33.3%) of CRCs MSI-H cases, respectively. Defects in hMLH1 expression in tumors were commonly associated with moderate differentiation. The p16 promoter was methylated in 4% of tumors. Conclusion: This is the first genetic study of CRC in this region of the world to demonstrate the incidence of MSI, p16 methylation, and hMLH1 and MSH2 expression in the Omani population. In addition, a relatively high frequency of CRC in younger age groups was noted, which is an important observation. The left-sided preponderance of MMR defective tumors was mostly associated with hMLH1, and with possible loss of hMSH2 expression, an observation that differs from studies on other populations. In conclusion, although the overall rate of CRC is unknown in this region, the frequency of MSI in CRC in this region appears to be the same as in Caucasians in the USA.

KW - CRC

KW - MSI

KW - MSP

KW - Oman

KW - p16

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