Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability

Kim, Jung Ho; Rhee, Ye Young; Kim, Kyung Ju; Cho, Nam Yun; Lee, Hye Seung; Kang, Gyeong Hoon

doi:10.1111/apm.12284

Cited by 18 publications

(17 citation statements)

References 43 publications

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“…ANXA10 has recently been identified as a marker of sessile serrated adenomas/polyps of the colorectum. By immunohistochemistry analysis of ANXA10 expression status in 168 MSI CRCs, Kim et al [54] found 17% of tumors exhibited positive ANXA10. Most of them were located in the right colon (96%; P < 0.001), as well as being significantly associated with CIMP phenotype (P < 0.001).…”

Section: Other Genesmentioning

confidence: 99%

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

Shen¹

2015

WJG

181

183

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The colon is derived from the embryological midgut and hindgut separately, with the right colon and left colon having different features with regards to both anatomical and physiological characteristics. Cancers located in the right and left colon are referred to as right colon cancer (RCC) and left colon cancer (LCC), respectively, based on their apparent anatomical positions. Increasing evidence supports the notion that not only are there differences in treatment strategies when dealing with RCC and LCC, but molecular features also vary between them, not to mention the distinguishing clinical manifestations. Disease-free survival after radical surgery of both RCC and LCC are similar. In the treatment of RCC, the benefit gained from adjuvant FOLFIRI chemotherapy is superior, or at least similar, to LCC, but inferior to LCC if FOLFOX regimen is applied. On the other hand, metastatic LCC exhibits longer survival than that of RCC in a palliative chemotherapy setting. For KRAS wild-type cancers, LCC benefits more from cetuximab treatment than RCC. Moreover, advanced LCC shows a higher sensitivity to bevacizumab treatment in comparison with advanced RCC. Significant varieties exist at the molecular level between RCC and LCC, which may serve as the cause of all apparent differences. With respect to carcinogenesis mechanisms, RCC is associated with known gene types, such as MMR, KRAS, BRAF, and miRNA-31, while LCC is associated with CIN, p53, NRAS, miRNA-146a, miRNA-147b, and miRNA-1288. Regarding protein expression, RCC is related to GNAS, NQO1, telomerase activity, P-PDH, and annexin A10, while LCC is related to Topo I, TS, and EGFR. In addition, separated pathways dominate progression to relapse in RCC and LCC. Therefore, RCC and LCC should be regarded as two heterogeneous entities, with this heterogeneity being used to stratify patients in order for them to have the optimal, current, and novel therapeutic strategies in clinical practice. Additional research is needed to uncover further differences between RCC and LCC.

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Section: Other Genesmentioning

confidence: 99%

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

Shen¹

2015

WJG

181

183

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“…50 Although extensive exonal microsatellite alterations and increased point mutations caused by mismatch repair defects bestow very considerable overlap on the altered gene expression signatures between the 2 MSI-H subtypes, the serrated neoplasia pathway-associated gene signature can be found in the CIMP-H/MSI-H subtype. 51 Because serrated polyps, including hyperplastic polyps, sessile serrated adenomas, and traditional serrated adenomas, are associated with aberrant gastric-type differentiation, the (58) ,.001…”

Section: Molecular Subtypes Based On Combined Cimpmentioning

confidence: 99%

“…and loss of intestinal expression (CDX2 and KRT20 loss). 51,52 Furthermore, histologic features that differ between the 2 MSI-H subtypes include sheeting appearance, eosinophilic cytoplasm, acinar appearance, signet ring cell formation, and stratified nuclei. The first 4 of these features are more frequent in the CIMP-H/MSI-H subtype, whereas the last feature is more frequent in the CIMP-0,L/MSI-H subtype.…”

Section: Cimp-h/msi-h Subtype Is Characterized By a Gain Of Gastric Dmentioning

confidence: 99%

“…Immunohistochemical markers associated with the serrated neoplasia pathway include ANXA10, CLDN18, CTSE, MUC5AC, MUC6, TFF2, and VSIG2, which are overexpressed in hyperplastic polyps, sessile serrated adenoma/polyps, and traditional serrated adenomas, compared with conventional adenomas. 51,52,[65][66][67] Little information is available regarding the expression statuses of these markers in CIMP-L CRCs and the differential clinicopathologic features of CIMP-L CRCs associated with the expression of these markers. In summary, although the factors triggering the CIMP pathway are unknown, the CIMP pathway is associated with the right-sided colon, female sex, older age, and white patients.…”

Section: Prognostic Implications Of Molecularmentioning

confidence: 99%

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Molecular Subtypes of Colorectal Cancer and Their Clinicopathologic Features, With an Emphasis on the Serrated Neoplasia Pathway

Bae¹,

Kim²,

Kang

2016

Archives of Pathology &Amp; Laboratory Medicine

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-Because colorectal cancers arise from 2 different morphologic multistep carcinogenesis pathways with varying contributions from 3 different molecular carcinogenesis pathways, colorectal cancer is a heterogeneous and complex disease. Thus, molecular subtyping of colorectal cancers is an important approach to characterizing their heterogeneity with respect to not only prognosis and therapeutic response but also biology and natural history.

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“…Recent studies have shown that expression of annexin A10 is a reliable marker of SSAs and the serrated pathway of CRC,16 17 46–51 and loss of Hes-1 expression can reliably differentiate SSAs from HPs 52. Nourbakhsh and Minoo sought to interrogate the concept that at least some TSAs may arise in association with precursor HP or SSA lesions, particularly those that develop in the right colon, by applying these two stains to a series of polyps from the right side of the colon with mixed features of TSA and SSA (as defined by Rex et al ) 7 16.…”

Section: Introductionmentioning

confidence: 99%

Traditional serrated adenoma: an overview of pathology and emphasis on molecular pathogenesis

McCarthy

Serra

Chetty

2019

BMJ Open Gastroenterol

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ObjectiveTo provide an overview of the pathology and molecular pathogenesis of traditional serrated adenomas (TSA).DesignDescribe the morphology and molecules that play a role in their pathogenesis.ResultsThese exuberant polypoid lesions are typified by tall cells with deeply eosinophilic cytoplasm, elongated nuclei bearing delicate chromatin, ectopic crypt foci, deep clefting of the lining mucosa and an overall resemblance to small bowel mucosa.Broadly, TSAs arise via three mechanisms. They may be BRAF mutated and CpG island methylator phenotype (CIMP)-high: right sided, mediated through a microvesicular hyperplastic polyp or a sessile serrated adenoma, may also have RNF43 mutations and result in microsatellite stable (MSS) colorectal cancers (CRC). The second pathway that is mutually exclusive of the first is mediated through KRAS mutation with CIMP-low TSAs. These are left-sided TSAs, are not associated with another serrated polyp and result in MSS CRC. These TSAs also have RSPO3, RNF43 and p53 mutations together with aberrant nuclear localisation of β-catenin. Third, there is a smaller group of TSAs that are BRAF and KRAS wild type and arise by as yet unknown molecular events. All TSAs show retention of mismatch repair proteins.ConclusionThese are characteristic unusual polyps with a complex molecular landscape.

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Annexin A10 expression correlates with serrated pathway features in colorectal carcinoma with microsatellite instability

Cited by 18 publications

References 43 publications

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

Different treatment strategies and molecular features between right-sided and left-sided colon cancers

Molecular Subtypes of Colorectal Cancer and Their Clinicopathologic Features, With an Emphasis on the Serrated Neoplasia Pathway

Traditional serrated adenoma: an overview of pathology and emphasis on molecular pathogenesis

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