Colitis-associated colorectal adenocarcinomas are frequently associated with non-intestinal mucin profiles and loss of SATB2 expression

Iwaya, Mai; Ota, Hiroyoshi; Tateishi, Yoko; Nakajima, Takahito; Riddell, Robert H.; Conner, James

doi:10.1038/s41379-018-0198-0

Cited by 22 publications

(41 citation statements)

References 25 publications

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“…A group led by Robert Riddell reported an association of villous adenomatous dysplasia with mucinous carcinoma and goblet cell-depleted dysplasia with low-grade tubuloglandular carcinoma 44. Another recent study from the same group reported loss of SATB2 expression in more than half of IBD-CRCs,45 which is also different from our precursor lesion study in which SATB2 loss was seen in only 15% of the non-adenomatous lesions in general. Whether the SATB2-negative CADs have a higher risk to progress to carcinoma may be an interesting question.…”

Section: Discussioncontrasting

confidence: 99%

Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

et al. 2019

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AimsInflammatory bowel disease (IBD)-associated precancerous lesions may be adenomatous or non-adenomatous with various histomorphologies. We aim to validate the newly proposed classification, to explore the neoplastic nature of the non-adenomatous lesions and to elucidate the molecular mechanisms underlying the different histomorphologies.Methods44 background precursor lesions identified in 53 cases of surgically resected IBD-associated colorectal and ileal carcinomas were reviewed for the histomorphological features (classified into adenomatous, mucinous, sessile serrated adenoma (SSA)-like, traditional serrated adenoma-like, differentiated, eosinophilic and serrated not otherwise specified (NOS)) and analysed for a key panel of colonic cancer-related molecular markers.ResultsApproximately 60% of the lesions were adenomatous, of which some had mixed serrated, mucinous or eosinophilic changes. The remaining non-adenomatous lesions, including all other types except SSA-like type, mostly showed mixed features and focal adenomatous dysplasia. KRAS mutation and p53 mutant-type expression were found in about half cases across all types, while PIK3CA mutation only in some of adenomatous and eosinophilic lesions and MLH1/PMS2 loss in a subset of adenomatous, mucinous and eosinophilic but not in differentiated and serrated lesions. SAT-B2 or PTEN loss and IMP3 overexpression were seen in a small subset of lesions. No BRAF, NRAS or EGFR gene mutation was detected in any type. Certain molecular-morphological correlations were demonstrated; however, no single or combined molecular alteration(s) was specific to any particular morphological type.ConclusionsIBD-associated precancerous lesions are heterogeneous both histologically and molecularly. True colitis-associated adenomatous lesions are unlikely conventional adenomas. Non-adenomatous lesions without frank cytologic dysplasia should also be regarded as neoplastic.

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Section: Discussioncontrasting

confidence: 99%

Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

et al. 2019

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“…Interestingly, SATB2 is also frequently lost in IBD-associated carcinomas, but is retained in most sporadic carcinomas. 19 Figure 2 shows an example of IBD-related dysplasia with loss of SATB2 staining.…”

Section: Tablementioning

confidence: 99%

Immunohistochemistry and special stains in gastrointestinal pathology practice

Liu¹,

Ghayouri²,

Brown³

2020

Diagnostic Histopathology

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“…[11,12] In keeping with this, we recently reported CAC tends to show non-conventional tumor morphology and loose intestinal markers such as SATB2 and CDX2, and show aberrant gastric mucin expression. [23] Ishibashi et al described the expression pro le of Atonal homolog-1 (ATOH1), a master transcription factor of the secretory lineage of intestinal epithelial cells, which retain their potential to revert to intestinal stem cells [24][25][26] in colitic mucosa. They identi ed both ATOH1 and LGR5 double positive tumor cells as well as LGR5 single positive tumor cells, suggesting that colitic tumors are mosaic and consisted of a heterogenous population of tumor stem cell.…”

Section: Discussionmentioning

confidence: 99%

“…H&E sections were reviewed at a multiheaded microscope by four gastrointestinal pathologists (MI, HO, RR, and JC) and each invasive carcinoma was subclassi ed by consensus into one of ve morphologic subtypes: conventional, mucinous, serrated, low grade tubuloglandular (LGTG) and others. [13] One representative para n block of tumor was selected in each case for RNA in situ hybridization (ISH).…”

Section: Cases Of Surgically Resected Colitis Associated Primary Colomentioning

confidence: 99%

Most colitis associated carcinomas lack expression of LGR5: implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma

Iwaya

Ota

Nakajima

et al. 2020

Preprint

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BackgroundLeucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5), a component of the Wnt receptor complex, is thought to lineage label gastric and intestinal stem cells. LGR5 expression is increased in colorectal carcinoma (CRC) compared to normal tissue. Colitis associated colorectal adenocarcinoma (CAC) often shows distinct morphologic and molecular phenotypes compared to sporadic cases. However, the expression profile of LGR5, and by extension the potential role of an intestinal stem cell phenotype, has not been well described in a series of human CAC. MethodRNA in situ hybridization (ISH) for LGR5 expression on 30 CACs (12 cases with conventional morphology and 18 cases with non-conventional type morphology) from 29 inflammatory bowel disease (IBD) patients was performed and compared the expression profile to a control group of 10 sporadic CRCs. ResultLGR5 was positive in 30% (9/30) of CAC cases and 90% (9/10) of sporadic CRCs (p=0.002). A large majority (89%) of LGR5 positive CACs were of the conventional histologic type, and conventional type CAC showed a significantly higher LGR5 score (median 3.0; interquartile range 1.75-3.25) than non-conventional type CAC (median 1.5; interquartile range 1.00-2.00) (p = 0.034). CAC with conventional morphology did have a lower level of LGR5 expression than sporadic CRC. Sporadic CRCs showed a significantly higher LGR5 level score than non-conventional type CACs (p <0.001). ConclusionThese findings suggest that the wider spectrum of tumor morphology in CAC may be associated with absence of a LGR5-expressing intestinal stem cell phenotype.

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Colitis-associated colorectal adenocarcinomas are frequently associated with non-intestinal mucin profiles and loss of SATB2 expression

Cited by 22 publications

References 25 publications

Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

Histological and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

Immunohistochemistry and special stains in gastrointestinal pathology practice

Most colitis associated carcinomas lack expression of LGR5: implications for unique pathways of carcinogenesis compared to sporadic colorectal carcinoma

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