Mutant specific anti calreticulin antibody (CAL2) immunohistochemistry as a screening test for calreticulin (CALR) mutation testing
© 2020 John Wiley & Sons Ltd..
BACKGROUND: About 50 different CALR frameshift mutations have been identified in BCR-ABL1 negative MPN, all leading to the development of common new protein C terminus. Antibody targeting this terminal epitope can be useful to identify this driver mutation using immunohistochemistry.
MATERIALS AND METHODS: CALR mutation analysis was carried out in 51 JAK2V617F negative cases, PMF (n = 22) and ET (n = 29). PCR followed by fragment analysis was performed for molecular detection of CALR mutation. Bone marrow biopsy specimens of corresponding patients were subjected to IHC using mutation specific antibody CAL2. Staining pattern and intensity were observed. Staining of <2% of background nonmegakaryocytic (non- MK) cells were regarded as Pattern A, while staining of more than 2% of background nonmegakaryocytic (non-MK) was regarded as pattern B.
RESULTS: CALR mutation was noted in 40.9% (9/22) and 41.4% (12/29) of JAK2V617F negative PMF and ET, respectively. All CALR mutated cases, irrespective of the mutation type, showed a positive IHC staining in the megakaryocytes with moderate to bright intensity. All CALR wild-type cases were negative on IHC. (Concordance rate- 100%). Pattern A was noted in 40% cases, while pattern B was noted in 60% cases. Pattern A staining had significantly higher chances of having type 1 mutation as compared to pattern B. In contrast, pattern B had a nonsignificant trend toward higher bone marrow cellularity and marrow fibrosis.
CONCLUSION: CAL2 IHC detects all types of CALR mutation. This can act as a sensitive, specific, rapid, and cost-effective screening test for CALR mutation analysis.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:42 |
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| Enthalten in: |
International journal of laboratory hematology - 42(2020), 5 vom: 17. Okt., Seite 604-611 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rahman, Khaliqur [VerfasserIn] |
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| Links: |
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| Themen: |
Antibodies, Monoclonal |
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| Anmerkungen: |
Date Completed 08.02.2021 Date Revised 03.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/ijlh.13242 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM310450640 |
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| 100 | 1 | |a Rahman, Khaliqur |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Mutant specific anti calreticulin antibody (CAL2) immunohistochemistry as a screening test for calreticulin (CALR) mutation testing |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Revised 03.05.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: About 50 different CALR frameshift mutations have been identified in BCR-ABL1 negative MPN, all leading to the development of common new protein C terminus. Antibody targeting this terminal epitope can be useful to identify this driver mutation using immunohistochemistry | ||
| 520 | |a MATERIALS AND METHODS: CALR mutation analysis was carried out in 51 JAK2V617F negative cases, PMF (n = 22) and ET (n = 29). PCR followed by fragment analysis was performed for molecular detection of CALR mutation. Bone marrow biopsy specimens of corresponding patients were subjected to IHC using mutation specific antibody CAL2. Staining pattern and intensity were observed. Staining of <2% of background nonmegakaryocytic (non- MK) cells were regarded as Pattern A, while staining of more than 2% of background nonmegakaryocytic (non-MK) was regarded as pattern B | ||
| 520 | |a RESULTS: CALR mutation was noted in 40.9% (9/22) and 41.4% (12/29) of JAK2V617F negative PMF and ET, respectively. All CALR mutated cases, irrespective of the mutation type, showed a positive IHC staining in the megakaryocytes with moderate to bright intensity. All CALR wild-type cases were negative on IHC. (Concordance rate- 100%). Pattern A was noted in 40% cases, while pattern B was noted in 60% cases. Pattern A staining had significantly higher chances of having type 1 mutation as compared to pattern B. In contrast, pattern B had a nonsignificant trend toward higher bone marrow cellularity and marrow fibrosis | ||
| 520 | |a CONCLUSION: CAL2 IHC detects all types of CALR mutation. This can act as a sensitive, specific, rapid, and cost-effective screening test for CALR mutation analysis | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a CAL2 IHC | |
| 650 | 4 | |a calreticulin (CALR) mutation | |
| 650 | 4 | |a essential thrombocythemia | |
| 650 | 4 | |a primary myelofibrosis | |
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| 700 | 1 | |a Singh, Manish Kumar |e verfasserin |4 aut | |
| 700 | 1 | |a Gupta, Ruchi |e verfasserin |4 aut | |
| 700 | 1 | |a Sharma, Akhilesh |e verfasserin |4 aut | |
| 700 | 1 | |a Paul, Pradeep |e verfasserin |4 aut | |
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| 700 | 1 | |a Nityanand, Soniya |e verfasserin |4 aut | |
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