Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer

Tuppurainen, Karoliina; Mäkinen, Johanna M.; Junttila, Oili E.; Liakka, Annikki; Kyllönen, Atte P.; Tuominen, Hannu; Karttunen, Tuomo J.; Mäkinen, Markus J.

doi:10.1002/path.1850

Cited by 121 publications

(187 citation statements)

References 25 publications

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“…Thus, many of the invasive carcinomas in our series were diagnosed as serrated adenocarcinomas. Most serrated adenocarcinomas examined previously were microsatellite-stable or had low levels of microsatellite instability with KRAS or BRAF mutation, 14,23 which are molecular features similar to those of the traditional serrated adenomas with cytologic dysplasia studied here. Traditional serrated adenoma is therefore likely to be a precursor of serrated adenocarcinoma.…”

Section: Discussionsupporting

confidence: 57%

“…1,9,23 Tumor location was divided as right side (cecum, ascending and transverse colon) and left side (descending, sigmoid colon and rectum).…”

Section: Case Selectionmentioning

confidence: 99%

“…Tumor necrosis in 410% of the lesion was detected in only two cases (3%) and the prominent 'dirty' necrosis commonly seen in conventional colorectal carcinoma was not identified in any of the cases. Eleven out of the 28 cases (39%) were diagnosed as serrated adenocarcinoma by the morphological criteria of epithelial serration, abundant eosinophilic cytoplasm and o10% necrosis 9,23 (Figure 2c). The tumor cells of the serrated adenocarcinomas typically had vesicular nuclei with a condensed nuclear membrane and distinct single nucleoli (Figure 2d).…”

Section: Morphological Features Of Invasive Carcinoma Arising From Trmentioning

confidence: 99%

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Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

et al. 2014

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Traditional serrated adenoma is one type of colorectal serrated neoplasm and a precursor of colorectal cancer. We evaluated the pathologic and molecular features of 60 traditional serrated adenomas with cytologic dysplasia and/or invasive carcinoma. On the basis of morphological features, 16 cases (27%) were categorized as traditional serrated adenoma with serrated dysplasia and 25 cases (42%) as traditional serrated adenoma with conventional adenomatous dysplasia. In addition, 19 cases (31%) showed an overall tubulovillous adenomatous structure but with focal serrated feature. Traditional serrated adenoma with serrated dysplasia had a significantly higher frequency of BRAF mutation than traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature (P ¼ 0.006), whereas traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature had higher frequencies of KRAS mutation than traditional serrated adenoma with serrated dysplasia (Po0.0001). Only traditional serrated adenoma with serrated dysplasia showed sessile serrated adenoma-like lesions at the periphery (n ¼ 3) and developed invasive carcinomas when the lesions were o15 mm in size. Abnormal nuclear accumulation of b-catenin was detected in traditional serrated adenoma with conventional adenomatous dysplasia and tubulovillous adenoma with serrated feature but not in traditional serrated adenoma with serrated dysplasia. The frequency of the positive CpG island methylator phenotype was similar among the three dysplastic subtypes, and immunostaining of four mismatch repair proteins in the nucleus was retained in all traditional serrated adenomas and associated invasive malignancies. Traditional serrated adenoma-associated adenocarcinomas (n ¼ 28) displayed distinctive morphological features: oval cell nuclei, serrated glands, infiltrating borders, rare occurrences of necrosis and mucinous differentiation. Overexpression of p53 was detected only in high-grade dysplasia and invasive adenocarcinoma. Our findings indicate that traditional serrated adenoma is a heterogeneous neoplasm with two pathways of neoplastic progression, which are distinct from the sessile serrated pathway of colorectal carcinogenesis.

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Section: Discussionsupporting

confidence: 57%

“…1,9,23 Tumor location was divided as right side (cecum, ascending and transverse colon) and left side (descending, sigmoid colon and rectum).…”

Section: Case Selectionmentioning

confidence: 99%

Section: Morphological Features Of Invasive Carcinoma Arising From Trmentioning

confidence: 99%

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Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

et al. 2014

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“…A first candidate is the sessile serrated pathway, which in the colon is mostly prominent in right-sided tumors and may be responsible for up to 16% of all proximal colonic tumors. 10 Rightsided tumors have a clearly lower rate of metastasis, and with about 15% of these tumors occurring through the sessile serrated pathway, this could explain the more indolent course of right-sided tumors in general, although evidence proving this effect is still too sparse to allow the assumption of a causal relationship. However, although we do not have specific pathologic data on previous polyps resected from patients in our cohort, we did note a markedly higher rate of preexisting polyposis in those patients with right-sided tumors, which supports this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Variations in Metastasis Site by Primary Location in Colon Cancer

Amri

Bordeianou

Sylla

et al. 2015

Journal of Gastrointestinal Surgery

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In primary tumors of the colon, the presence of locoregional and distant metastasis has important consequences for the prognosis and the preferred treatment approach for the individual patient. 1 In the absence of clinical and radiological suspicion of distant metastasis, treatment will be surgical with curative intent in virtually all cases. If lymphatic disease is also absent in the surgical resection specimen, adjuvant therapy is rarely required and most patients will only need regular follow-up to monitor recurrence.Colonic malignancies have a tendency to spread to the pericolic lymphatics, followed by more distant lymph node stations, with distant hematologic spread usually seen as a last stage of dissemination. These steps are however not obligatorily sequential, nor is lymphatic spread a prerequisite of distant metastasis, as hematologic spread can occur in the absence of involved lymph nodes, even in necropsies. 2 Distant metastatic spread is present in about one in five patients at baseline, 3 most often to the liver, followed by the lungs and the peritoneum. Less typical sites of metastasis once colonic tumor cells reach the systemic arterial circulation are numerous and include the bones and bone marrow, the brain, and more rarely other parts of the gastrointestinal tract, as well as other solid organs including the kidney, the spleen, and adrenal glands.Despite being studied in detail, most of the research aimed at identifying patterns of metastasis combine patients affected by cancers of the colon and rectum. 4 If colonic malignancies are studied separately, it will commonly be done by clustering all regions of the colon together.Considering that lymphovascular drainage passes through distinct and anatomically discrete vessels for right-sided, left sided and sigmoid tumors, it could potentially have a significant impact on the specific rates and patterns of metastatic spread. Our aim in this study is to verify whether metastasis patterns differ for each of the major resection regions in malignancies of the colon.

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“…Progression of hyperplastic polyps and serrated adenomas into carcinoma has been reported (Ma¨kinen et al, 2001). Adenocarcinomas displaying serrated features seem to account for up to 7.5% of all CRCs, making it a significant subgroup of CRC (Ma¨kinen et al, 2001;Tuppurainen et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis

et al. 2006

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Serrated colorectal carcinomas (CRCs) are morphologically different from conventional CRCs and have been proposed to follow a distinct pathway of CRC formation. Despite studies of single molecular events in this tumor type, the diagnosis of serrated CRC relies on morphology and the putative unique biological character of these tumors has not been established. Here we show that the gene expression profiling of 37 CRCs separated serrated and conventional CRCs into two distinct branches in unsupervised hierarchical clustering (P-value 7.8 Â 10 À7 ), and revealed 201 differentially expressed genes representing potential biomarkers for serrated CRC. Immunohistochemistry was utilized to verify the key findings in the 37 CRCs examined by expression profiling, and a separate validation set of 37 serrated and 86 conventional CRCs was examined to evaluate the candidate biomarkers in an extended sample material. Ephrin receptor B2, hypoxia-inducible factor 1-alpha and patched appeared as proteins important for genesis of serrated CRC. This study establishes serrated CRCs as a biologically distinct subclass of CRC and represents a step forward in the molecular classification of these cancers. The study also provides a platform to understand the molecular basis of serrated CRC and in long term may contribute to the development of specific treatment options for this tumor type.

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Morphology and microsatellite instability in sporadic serrated and non-serrated colorectal cancer

Cited by 121 publications

References 25 publications

Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

Traditional serrated adenoma has two pathways of neoplastic progression that are distinct from the sessile serrated pathway of colorectal carcinogenesis

Variations in Metastasis Site by Primary Location in Colon Cancer

Serrated carcinomas form a subclass of colorectal cancer with distinct molecular basis

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