Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC)
Purpose. Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. Methods. This study targeted c...
Saved in:
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2020-01-01
|
| Series: | Gastroenterology Research and Practice |
| Online Access: | http://dx.doi.org/10.1155/2020/5632984 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850220028442443776 |
|---|---|
| author | Bayan Maraqa Ghassan Al-Shbool Osama Abu-Shawer Mamoun Souleiman Osama Alshakhatreh Amal Al-Omari Hadeel Abdelkhaleq Ayat Taqash Maysa Al-Hussaini |
| author_facet | Bayan Maraqa Ghassan Al-Shbool Osama Abu-Shawer Mamoun Souleiman Osama Alshakhatreh Amal Al-Omari Hadeel Abdelkhaleq Ayat Taqash Maysa Al-Hussaini |
| author_sort | Bayan Maraqa |
| collection | DOAJ |
| description | Purpose. Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. Methods. This study targeted cases of CRC at King Hussein Cancer Center from 2004 until 2012 in patients 45 years of age or younger at the time of diagnosis. Clinicopathological data was obtained from 155 patients’ records. Immunohistochemistry for MLH1, MSH2, PMS2, and MSH6 proteins was performed on paraffin-embedded tissue containing carcinoma. Results. The median age of patient at diagnosis was 38 years. A total of 29 (19%) cases showed deficient MMRP(dMMRP)expression. Loss of expression of PMS2 was seen in 17 cases, 12 cases of which showed loss of MLH1 expression. Loss of expression of MSH6 was seen in 10 cases, 9 of which showed loss of MSH2 expression. One case (3.4%) showed loss of all four MMR proteins, and another case (3.4%) showed loss of PMS2/MLH1 and MSH6. There was a significant association between abnormal MMR protein expression and tumor location proximal to splenic flexure (p value 0.000), pathologic features suggestive of microsatellite instability (p value 0.000), P53 negativity (p value 0.000), and stage (p value 0.02). Patients with dMMRP CRC appeared to have a significantly better overall survival compared to patients with proficient MMRP(pMMRP)(p value 0.02). Loss of MSH2/MSH6 was significantly associated with positive family history of cancer (p value = 0.020). Conclusions. The prevalence of dMMRP tumors in this age group appears to be similar to international literature. dMMRP tumors tends to be associated with earlier stages and better outcomes compared to pMMRP cases. dMMRP can serve as a biomarker for better prognosis. These results are of value in directing the clinical management of young patients with CRC. |
| format | Article |
| id | doaj-art-7d40867c4f6e4c8aa012de9860295383 |
| institution | OA Journals |
| issn | 1687-6121 1687-630X |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Gastroenterology Research and Practice |
| spelling | doaj-art-7d40867c4f6e4c8aa012de98602953832025-08-20T02:07:12ZengWileyGastroenterology Research and Practice1687-61211687-630X2020-01-01202010.1155/2020/56329845632984Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC)Bayan Maraqa0Ghassan Al-Shbool1Osama Abu-Shawer2Mamoun Souleiman3Osama Alshakhatreh4Amal Al-Omari5Hadeel Abdelkhaleq6Ayat Taqash7Maysa Al-Hussaini8Department of Pathology, King Hussein Cancer Center, Amman, JordanMedStar Washington Hospital Center/Georgetown University, USAUniversity of Jordan School of Medicine, JordanUniversity of Jordan School of Medicine, JordanUniversity of Jordan School of Medicine, JordanOffice of Scientific Affairs and Research, King Hussein Cancer Center (KHCC), Amman, JordanOffice of Scientific Affairs and Research, King Hussein Cancer Center (KHCC), Amman, JordanOffice of Scientific Affairs and Research, King Hussein Cancer Center (KHCC), Amman, JordanDepartment of Pathology, King Hussein Cancer Center, Amman, JordanPurpose. Microsatellite instability (MSI) caused by mismatch repair protein (MMRP) deficiency is detected in 15% of sporadic colorectal cancers (CRCs). Our aim is to investigate the frequency of MMRP deficiency in young CRC patients, using immunohistochemical analysis. Methods. This study targeted cases of CRC at King Hussein Cancer Center from 2004 until 2012 in patients 45 years of age or younger at the time of diagnosis. Clinicopathological data was obtained from 155 patients’ records. Immunohistochemistry for MLH1, MSH2, PMS2, and MSH6 proteins was performed on paraffin-embedded tissue containing carcinoma. Results. The median age of patient at diagnosis was 38 years. A total of 29 (19%) cases showed deficient MMRP(dMMRP)expression. Loss of expression of PMS2 was seen in 17 cases, 12 cases of which showed loss of MLH1 expression. Loss of expression of MSH6 was seen in 10 cases, 9 of which showed loss of MSH2 expression. One case (3.4%) showed loss of all four MMR proteins, and another case (3.4%) showed loss of PMS2/MLH1 and MSH6. There was a significant association between abnormal MMR protein expression and tumor location proximal to splenic flexure (p value 0.000), pathologic features suggestive of microsatellite instability (p value 0.000), P53 negativity (p value 0.000), and stage (p value 0.02). Patients with dMMRP CRC appeared to have a significantly better overall survival compared to patients with proficient MMRP(pMMRP)(p value 0.02). Loss of MSH2/MSH6 was significantly associated with positive family history of cancer (p value = 0.020). Conclusions. The prevalence of dMMRP tumors in this age group appears to be similar to international literature. dMMRP tumors tends to be associated with earlier stages and better outcomes compared to pMMRP cases. dMMRP can serve as a biomarker for better prognosis. These results are of value in directing the clinical management of young patients with CRC.http://dx.doi.org/10.1155/2020/5632984 |
| spellingShingle | Bayan Maraqa Ghassan Al-Shbool Osama Abu-Shawer Mamoun Souleiman Osama Alshakhatreh Amal Al-Omari Hadeel Abdelkhaleq Ayat Taqash Maysa Al-Hussaini Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) Gastroenterology Research and Practice |
| title | Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) |
| title_full | Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) |
| title_fullStr | Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) |
| title_full_unstemmed | Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) |
| title_short | Frequency of Mismatch Repair Protein (MMRP) Deficiency among Young Jordanians Diagnosed with Colorectal Carcinoma (CRC) |
| title_sort | frequency of mismatch repair protein mmrp deficiency among young jordanians diagnosed with colorectal carcinoma crc |
| url | http://dx.doi.org/10.1155/2020/5632984 |
| work_keys_str_mv | AT bayanmaraqa frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT ghassanalshbool frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT osamaabushawer frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT mamounsouleiman frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT osamaalshakhatreh frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT amalalomari frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT hadeelabdelkhaleq frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT ayattaqash frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc AT maysaalhussaini frequencyofmismatchrepairproteinmmrpdeficiencyamongyoungjordaniansdiagnosedwithcolorectalcarcinomacrc |