Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas
<p>Abstract</p> <p>Background</p> <p>MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-06-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/9/184 |
| _version_ | 1811296323719135232 |
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| author | Tops Carli MJ van Eijk Ronald van Wezel Tom Middeldorp Anneke Jordanova Ekaterina S van Puijenbroek Marjo de Miranda Noel FCC Nielsen Maartje Vasen Hans FA Hes Frederik J Morreau Hans |
| author_facet | Tops Carli MJ van Eijk Ronald van Wezel Tom Middeldorp Anneke Jordanova Ekaterina S van Puijenbroek Marjo de Miranda Noel FCC Nielsen Maartje Vasen Hans FA Hes Frederik J Morreau Hans |
| author_sort | Tops Carli MJ |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs.</p> <p>Methods</p> <p>From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. <it>KRAS2</it>, the mutation cluster region (MCR) of <it>APC, p53</it>, and <it>SMAD4 </it>were analyzed for somatic mutations.</p> <p>Results</p> <p>MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic <it>APC </it>MCR mutations occurred in 14% (5/36) while 64% (23/36) had <it>KRAS2 </it>mutations (22/23 c.34G>T). G>T tranversions were found in <it>p53 </it>and <it>SMAD4</it>, although the relative frequency compared to other mutations was low.</p> <p>Conclusion</p> <p>MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in <it>APC </it>and <it>KRAS2 </it>(mutated in early tumour development) but not in <it>P53 </it>and <it>SMAD4 </it>(implicated in tumour progression) might indicate a predominant MUTYH effect in <it>early </it>carcinogenesis.</p> |
| first_indexed | 2024-04-13T05:46:36Z |
| format | Article |
| id | doaj.art-630b9dd6351f433f8e336352873bfa3e |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-13T05:46:36Z |
| publishDate | 2009-06-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-630b9dd6351f433f8e336352873bfa3e2022-12-22T02:59:56ZengBMCBMC Cancer1471-24072009-06-019118410.1186/1471-2407-9-184Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomasTops Carli MJvan Eijk Ronaldvan Wezel TomMiddeldorp AnnekeJordanova Ekaterina Svan Puijenbroek Marjode Miranda Noel FCCNielsen MaartjeVasen Hans FAHes Frederik JMorreau Hans<p>Abstract</p> <p>Background</p> <p>MUTYH-associated polyposis (MAP) is a recessively inherited disorder which predisposes biallelic carriers for a high risk of polyposis and colorectal carcinoma (CRC). Since about one third of the biallelic MAP patients in population based CRC series has no adenomas, this study aimed to identify specific clinicopathological characteristics of MAP CRCs and compare these with reported data on sporadic and Lynch CRCs.</p> <p>Methods</p> <p>From 44 MAP patients who developed ≥ 1 CRCs, 42 of 58 tumours were analyzed histologically and 35 immunohistochemically for p53 and beta-catenin. Cell densities of CD3, CD8, CD57, and granzyme B positive lymphocytes were determined. <it>KRAS2</it>, the mutation cluster region (MCR) of <it>APC, p53</it>, and <it>SMAD4 </it>were analyzed for somatic mutations.</p> <p>Results</p> <p>MAP CRCs frequently localized to the proximal colon (69%, 40/58), were mucinous in 21% (9/42), and had a conspicuous Crohn's like infiltrate reaction in 33% (13/40); all of these parameters occurred at a higher rate than reported for sporadic CRCs. Tumour infiltrating lymphocytes (TILs) were also highly prevalent in MAP CRCs. Somatic <it>APC </it>MCR mutations occurred in 14% (5/36) while 64% (23/36) had <it>KRAS2 </it>mutations (22/23 c.34G>T). G>T tranversions were found in <it>p53 </it>and <it>SMAD4</it>, although the relative frequency compared to other mutations was low.</p> <p>Conclusion</p> <p>MAP CRCs show some similarities to micro-satellite unstable cancers, with a preferential proximal location, a high rate of mucinous histotype and increased presence of TILs. These features should direct the practicing pathologist towards a MAP aetiology of CRC as an alternative for a mismatch repair deficient cause. High frequent G>T transversions in <it>APC </it>and <it>KRAS2 </it>(mutated in early tumour development) but not in <it>P53 </it>and <it>SMAD4 </it>(implicated in tumour progression) might indicate a predominant MUTYH effect in <it>early </it>carcinogenesis.</p>http://www.biomedcentral.com/1471-2407/9/184 |
| spellingShingle | Tops Carli MJ van Eijk Ronald van Wezel Tom Middeldorp Anneke Jordanova Ekaterina S van Puijenbroek Marjo de Miranda Noel FCC Nielsen Maartje Vasen Hans FA Hes Frederik J Morreau Hans Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas BMC Cancer |
| title | Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| title_full | Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| title_fullStr | Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| title_full_unstemmed | Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| title_short | Colorectal carcinomas in MUTYH-associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| title_sort | colorectal carcinomas in mutyh associated polyposis display histopathological similarities to microsatellite unstable carcinomas |
| url | http://www.biomedcentral.com/1471-2407/9/184 |
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