Sessile serrated adenoma/polyps: Where are we at in 2016?

It is currently known that colorectal cancers(CRC) arise from 3 different pathways: the adenoma to carcinoma chromosomal instability pathway(50%-70%); the mutator "Lynch syndrome" route(3%-5%); and the serrated pathway(30%-35%). The World Health Organization has classified serrated polyps into three types of lesions: hyperplastic polyps(HP),sessile serrated adenomas/polyps(SSA/P) and traditional serrated adenomas(TSA),the latter two strongly associated with development of CRCs. HPs do not cause cancer and TSAs are rare. SSA/P appear to be the responsible precursor lesion for the development of cancers through the serrated pathway. Both HPs and SSA/Ps appear morphologically similar. SSA/P are difficult to detect. The margins are normally inconspicuous. En bloc resection of these polyps can hence be troublesome. A careful examination of borders,submucosal injection of a dye solution(for larger lesions) and resection of a rim of normal tissue around the lesion may ensure total eradication of these lesions.     

Pathogenesis and Management of Serrated Polyps: Current Status and Future Directions

Hyperplastic or serrated polyps were once believed to have little to no clinical significance. A subset of these polyps are now considered to be precursors to colorectal cancers (CRC) in the serrated pathway that may account for at least 15% of all tumors. The serrated pathway is distinct from the two other CRC pathways and involves an epigenetic hypermethylation mechanism of CpG islands within promoter regions of tumor suppressor genes. This process results in the formation of CpG island methylator phenotype tumors. Serrated polyps are divided into hyperplastic polyps, sessile serrated adenomas/polyps (SSA/Ps), and traditional serrated adenomas (TSAs). The SSA/P and the TSA have the potential for dysplasia and subsequent malignant transformation. The SSA/Ps are more common and are more likely to be flat than TSAs. Their flat morphology may make them difficult to detect and thus explain the variation in detection rates among endoscopists. Challenges for endoscopists also include the difficulty in pathological interpretation as well surveillance of these lesions. Furthermore, serrated polyps may be inadequately resected by endoscopists. Thus, it is not surprising that the serrated pathway has been linked with interval cancers. This review will provide the physician or clinician with the knowledge to manage patients with serrated polyps.     

Serrated polyps of the colon and rectum: Remove or not?

In recent years, the serrated neoplasia pathway where serrated polyps arise as a colorectal cancer has gained considerable attention as a new carcinogenic pathway. Colorectal serrated polyps are histopathologically classified into hyperplastic polyps(HPs), sessile serrated lesions, and traditional serrated adenomas; in the serrated neoplasia pathway, the latter two are considered to be premalignant. In western countries, all colorectal polyps, including serrated polyps, apart from diminutive rectosigmoid HPs are removed. However, in Asian countries, the treatment strategy for colorectal serrated polyps has remained unestablished. Therefore, in this review, we described the clinicopathological features of colorectal serrated polyps and proposed to remove HPs and sessile serrated lesions ≥ 6 mm in size, and traditional serrated adenomas of any size.     

Serrated polyps of the colon and rectum: Endoscopic features including image enhanced endoscopy

In this review, I outline the characteristic endoscopic findings of serrated lesions of the colorectum based on image enhanced endoscopy(IEE). Histopathologically, lesions with serrated structures are typically classified into the following three types based: hyperplastic polyps(HPs), traditional serrated adenomas(TSAs), and sessile serrated adenoma/polyps(SSA/Ps). Both HP and SSA/P often present as dark-green colors on auto fluorescence imaging(AFI) colonoscopy that are similar to the normal surrounding mucosa. In contrast, TSAs often have elevated shapes and present as magenta colors that are similar to the tubular adenomas. The superficial type of TSA also includes many lesions that present as magenta colors. When SSA/Ps are associated with cytological dysplasia, many lesions present with magenta colors, whereas lesions that are not associated with cytological dysplasia present with dark-green colors. When observed via narrow band imaging(NBI), many SSA/P include lesions with strong mucous adhesions. Because these lesions are observed with reddish mucous adhesions, we refer to them as "red cap sign" and place such signs among the typical findings of SSA/P. Because the dilatation of the pit in SSA/P is observed as a round/oval black dot on magnified observations, we refer to this finding as Ⅱ-dilatation pit(Ⅱ-D pit) and also positioned it as a characteristic finding of SSA/P. In contrast, dilatations of the capillary vessels surrounding the glands, such as those that occur in tubular adenoma, are not considered to be useful for differentiating HPs from SSA/Ps. However, in cases in which SSA/P is associated with cytological dysplasia, the dilatation of capillary vessels is observed in the same area. When submucosal layer invasion occurs in the same area, the blood flow presents with irregularities that are similar to those of common colorectal cancer at an early stage and disappears as the invasion proceeds deeply. The surface pattern of invasive cancer that is observed at the tumor surface is also likely to disappear. Based on the above results, we considered that the differentiations between HP and TSA, between TSA and SSA/P, and between HP and SSA/P might become easier due to the concomitant use of white light observation and IEE. We also concluded that AFI and NBI can be useful modalities for SSA/P lesions associated with cytological dysplasia.     

Clinicopathological characteristics of serrated polyps as precursors to colorectal cancer: Current status and management

Serrated polyps have long been thought to lack malignant potential in the human colorectum. However, identification of the serrated pathway to colorectal cancer based on molecular biology has improved our understanding of the pathogenesis of colorectal cancers. Accordingly, serrated polyps such as traditional serrated adenoma and sessile serrated adenoma/polyps (SSA/P) are now considered to be precursor lesions of the serrated pathway. Recently, serrated polyps were classified into three subtypes, consisting of hyperplastic polyp, SSA/P, and traditional serrated adenoma, according to the World Health Organization classification. It has been suggested that SSA/P in the proximal colon are a precursor lesion of pathogenesis of colorectal cancer and are characterized by BRAF mutation and a CpG island methylator phenotype with or without microsatellite instability. However, SSA/P is more challenging to detect by colonoscopy and is likely to account for some interval cancers, particularly in the proximal colon because it presents flat or sessile, isochroous appearance, and occasionally has a mucous cap. Furthermore, the possibility has been raised that pathologists misclassify SSA/P as hyperplastic polyp. It is important for gastroenterologists to recognize the endoscopic features of serrated polyps to facilitate their detection and removal and also to establish postpolypectomy surveillance guidelines. In this review, we discuss the recent classification of serrated polyps; the molecular characteristics of the serrated pathway; appropriate diagnostic methods using endoscopy, including a new image‐enhanced endoscopic technique; and management of these lesions.     

Expression of Cytokeratins 7 and 20 in Serrated Adenoma and Related Diseases

The entity of serrated adenoma of the colorectum was first proposed in 1990, and it was characterized as epithelial neoplasia combining the architectural features of a hyperplastic polyp with the cytological features of an adenoma. Over the past few years, various clinicopathological studies on serrated adenoma have been reported, but its histogenesis remains unclear. Recently the existence of a “serrated neoplasia pathway” leading to malignancy, which is different from the so-called adenoma–carcinoma sequence, has been discussed. Yao et al. reported that hyperplastic polyps and serrated adenomas share a common cell lineage with gastric differentiation. To clarify the existence of the serrated neoplasia pathway, we performed immunohistochemical staining of cytokeratin 7 (CK7) and cytokeratin 20 (CK20), which are commonly used to determine the primary site of a metastatic lesion, and we examined the pattern of CK7/CK20 expression in various colorectal lesions including 44 serrated adenomas, 25 hyperplastic polyps, 20 traditional adenomas, and 48 carcinomas. An obvious difference existed in the pattern of CK7/CK20 expression between the serrated lesions (hyperplastic polyps and serrated adenomas) and others. The majority of serrated adenomas and hyperplastic polyps presented a CK7+/CK20+ pattern, whereas most conventional adenomas and adenocarcinomas expressed CK7−/CK20+. Adenocarcinoma developing in serrated adenoma also presented a CK7+/CK20+ pattern. There are several reports that CK7 is a possible marker of transient dedifferentiation in the gastric carcinogenesis process. Taken together with the present results, a distinct pathway of colorectal carcinogenesis must exist, which is different from the adenoma–carcinoma sequence. CK7 is a possible marker for the serrated neoplasia pathway of colorectal carcinogenesis.     

Evaluation of magnifying colonoscopy in the diagnosis of serrated polyps

AIM: To elucidate the colonoscopic features of serrated lesions of the colorectum using magnifying colonoscopy.METHODS: Broad division of serrated lesions of the colorectum into hyperplastic polyps (HPs), traditional serrated adenomas (TSAs), and sessile serrated adenomas/polyps (SSA/Ps) has been proposed on the basis of recent molecular biological studies. However, few reports have examined the colonoscopic features of these divisions, including magnified colonoscopic findings. This study examined 118 lesions excised in our hospital as suspected serrated lesions after magnified observation between January 2008 and September 2011. Patient characteristics (sex, age), conventional colonoscopic findings (location, size, morphology, color, mucin) and magnified colonoscopic findings (pit pattern diagnosis) were interpreted by five colonoscopists with experience in over 1000 colonoscopies, and were compared with histopathological diagnoses. The pit patterns were categorized according to Kudo’s classification, but a more detailed investigation was also performed using the subclassification [type II-Open (type II-O), type II-Long (type II-L), or type IV-Serrated (type IV-S)] proposed by Kimura T and Yamano H.RESULTS: Lesions comprised 23 HPs (23/118: 19.5%), 39 TSAs (39/118: 33.1%: with cancer in one case), 50 SSA/Ps (50/118: 42.4%: complicated with cancer in three cases), and six others (6/118: 5.1%). We excluded six others, including three regular adenomas, one hamartoma, one inflammatory polyp, and one juvenile polyp for further analysis. Conventional colonoscopy showed that SSA/Ps were characterized as larger in diameter than TSAs and HPs (SSA/P vs HP, 13.62 ± 8.62 mm vs 7.74 ± 3.24 mm, P < 0.001; SSA/Ps vs TSA, 13.62 ± 8.62 mm vs 9.89 ± 5.73 mm, P < 0.01); common in the right side of the colon [HPs, 30.4% (7/23): TSAs, 20.5% (8/39): SSA/P, 84.0% (42/50), P < 0.001]; flat-elevated lesion [HPs, 30.4% (7/23): TSAs, 5.1% (2/39): SSA/Ps, 90.0% (45/50), P < 0.001]; normal-colored or pale imucosa [HPs, 34.8% (8/23): TSAs, 10.3% (4/39): SSA/Ps, 80% (40/50), P < 0.001]; and with large amounts of mucin [HPs, 21.7% (5/23): TSAs, 17.9% (7/39): SSA/Ps, 72.0% (36/50), P < 0.001]. In magnified colonoscopic findings, 17 lesions showed either type II pit pattern alone or partial type II pit pattern as the basic architecture, with 14 HPs (14/17, 70.0%) and 3 SSA/Ps. Magnified colonoscopy showed the type II-O pit pattern as characteristic of SSA/Ps [sensitivity 83.7% (41/49), specificity 85.7% (54/63)]. Cancer was also present in three lesions, in all of which a type VI pit pattern was also present within the same lesion. There were four HPs and four TSAs each. The type IV-S pit pattern was characteristic of TSAs [sensitivity 96.7% (30/31), specificity 89.9% (72/81)]. Cancer was present in one lesion, in which a type VI pit pattern was also present within the same lesion. In our study, serrated lesions of the colorectum also possessed the features described in previous reports of conventional colonoscopic findings. The pit pattern diagnosis using magnifying colonoscopy, particularly magnified colonoscopic findings using subclassifications of surface architecture, reflected the pathological characteristics of SSA/Ps and TSAs, and will be useful for colonoscopic diagnosis.CONCLUSION: We suggest that this system could be a good diagnostic tool for SSA/Ps using magnifying colonoscopy.     

Endoscopic diagnosis of sessile serrated adenoma/polyp with and without dysplasia/carcinoma

Sessile serrated adenoma/polyps(SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a Cp G island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ‘‘mucus cap', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their(semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.     

Differential expression of p53 and p504s in hyperplastic polyp, sessile serrated adenoma and traditional serrated adenoma

Aims  

Known collectively as serrated polyps, hyperplastic polyps (HP), sessile serrated adenomas (SSA/SSP) and traditional serrated adenoma (TSA) may represent a spectrum of increasing malignant potential with characteristic immunological markers. There is increasing evidence that HP, SSA/SSP and TSA are biologically different and are likely to represent a spectrum along the serrated polyp pathway. Although there is general consensus about the diagnostic features of serrated polyps, the morphological differences between the categories are often subtle. This study compares the expression of p53 and P504S among serrated polyps. Sixty seven randomly selected biopsies (n = 59) and resection specimens (n = 8) histologically diagnosed for SSA/SSP, TSA and HP (19, 30 and 18 specimens, respectively) were obtained.     

Sessile serrated adenoma/polyp showed rapid malignant transformation in the final 13 months

Based on the concept of the adenoma-carcinoma sequence, most colorectal cancers are considered to arise from conventional adenomas. However, recent studies suggested that a subset of colorectal cancers develop through the serrated neoplastic pathway. It has also been documented that serrated polyps can rapidly transform into invasive cancers even when they are small in size. We now describe a case of a sessile serrated adenoma/polyp which had been followed up for 4 years but eventually showed rapid transformation into an advanced cancer accompanied by a remarkable morphological change within only 13 months. Retrospective genetic and epigenetic analyses showed microsatellite instability, CpG island methylator phenotype-positive, and BRAF mutation in the lesion, suggesting the tumor had developed through the serrated neoplastic pathway. This case may provide valuable information about the natural history of sessile serrated adenoma/polyps which eventually progress to advanced cancers.     

High prevalence of sessile serrated adenomas with BRAF mutations: a prospective study of patients undergoing colonoscopy

BACKGROUND & AIMS: Sporadic colorectal cancers with a high degree of microsatellite instability are a clinically distinct subgroup with a high incidence of BRAF mutation and are widely considered to develop from serrated polyps. Previous studies of serrated polyps have been highly selected and largely retrospective. This prospective study examined the prevalence of sessile serrated adenomas and determined the incidence of BRAF and K-ras mutations in different types of polyps. METHODS: An unselected consecutive series of 190 patients underwent magnifying chromoendoscopy. Polyp location, size, and histologic classification were recorded. All polyps were screened for BRAF V600E and K-ras codon 12 and 13 mutations. RESULTS: Polyps were detected in 72% of patients. Most (60%) were adenomas (tubular adenomas, tubulovillous adenomas), followed by hyperplastic polyps (29%), sessile serrated adenomas (SSAs; 9%), traditional serrated adenomas (0.7%), and mixed polyps (1.7%). Adenomas were more prevalent in the proximal colon (73%), as were SSAs (75%), which tended to be large (64% >5 mm). The presence of at least one SSA was associated with increased polyp burden (5.0 vs 2.5; P < .0001) and female sex (P < .05). BRAF mutation was rare in adenomas (1/248 [0.4%]) but common in SSAs (78%), traditional serrated adenomas (66%), mixed polyps (57%), and microvesicular hyperplastic polyps (70%). K-ras mutations were significantly associated with goblet cell hyperplastic polyps and tubulovillous adenomas (P < .001). CONCLUSIONS: The prevalence of SSAs is approximately 9% in patients undergoing colonoscopy. They are associated with BRAF mutation, proximal location, female sex, and presence of multiple polyps. These findings emphasize the importance of identifying and removing these lesions for endoscopic prevention of colorectal cancer.     

Clinicopathological features,diagnosis, and treatment of sessile serrated adenoma/polyp with dysplasia/carcinoma

Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF‐mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to “interval cancers” and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.     

结直肠锯齿状病变的癌变机制及内镜诊断研究进展

结直肠锯齿状病变以往被认为是一种良性病变,近10年的研究表明其具有恶性潜能,锯齿状途径被认为是除腺瘤—癌、炎症—异型增生—癌变、de novo癌途径外新的结直肠癌癌变途径。据最新的世界卫生组织分类标准,锯齿状病变分为增生性息肉、无蒂锯齿状病变和传统锯齿状腺瘤3种类型。由于锯齿状病变具有相对特异的癌变途径及内镜下特点,本...     

Sessile serrated adenomas: Demographic, endoscopic and pathological characteristics

AIM:To study the demographic and endoscopic characteristics of patients with sessile serrated adenoma(SSA) in a single center.METHODS:Patients with SSA were identified by review of the pathology database of Mayo Clinic Arizona from 2005 to 2007.A retrospective chart review was performed to extract data on demographics,polyp characteristics,presence of synchronous adenomatous polyps or cancer,polypectomy methods,and related complications.RESULTS:One hundred and seventy-one(2.9%) of all patients undergoing co...     

Progression of a sessile serrated adenoma to an early invasive cancer within 8 months

Recent studies suggest that serrated polyps, including hyperplastic polyps, traditional serrated adenomas, and sessile serrated adenomas, may be morphologically and genetically distinct and linked to microsatellite unstable colorectal cancers, and thus the concept of a hyperplastic polyp–serrate adenoma–carcinoma pathway has been suggested. Furthermore, it has been suggested that transformation from serrated polyps to invasive cancers can be rapid and occurs when the lesions are small; however, direct evidence for this issue is scant. We herein describe a case of a sessile serrated adenoma showing rapid transformation into a submucosal invasive carcinoma with remarkable morphological change in a short period of 8 months. This case is unique and suggestive, as it provided information about the natural history of a sessile serrated adenoma.     

Serrated lesions of the colorectum, a new entity: what should a clinician/ endoscopist know about it ?

Serrated polyps of the colorectum have received much attention in recent literature. Several classifications have been proposed and created considerable confusion. Morphology and molecular biology have greatly contributed to the better identification of these entity. The recently published WHO classification, proposed using the term of "serrated polyp" as a generic term and defined sporadic serrated polyps as "a heterogeneous group" of lesions characterized morphologically by a serrated (sawtooth or stellate) architecture of the epithelial component which include hyperplastic polyps (HP), sessile serrated adenomas/polyps (SSA/P) and traditional serrated adenomas (TSA). With the development of molecular biology, it is now clear that the serrated pathway is one of the new carcinogenic pathways in the colon. There is now strong evidence that some serrated polyps correspond to precursors of some sporadic colorectal cancer (CRC). The aim of this article is to summarize the present data concerning the morphological and molecular characteristics of these serrated lesions and to give some recommendations for the management of such lesions.     

Serrated polyps – a concealed but prevalent precursor of colorectal cancer

Serrated polyps have long been considered to lack malignant potential but accumulating data suggest that these lesions may cause up to one-third of all sporadic colorectal cancer. Serrated polyps are classified into three subtypes, including sessile serrated adenomas/polyps (SSA/Ps), traditional serrated adenomas (TSAs), and hyperplastic polyps (HPs). SSA/P and TSA harbour malignant potential but TSA represents only 1–2%, wheras SSA/P constitute up to 20% of all serrated lesions. HPs are most common (80%) of all serrated polyps but are considered to have a low potential of developing colorectal cancer. Due to their subtle appearence, detection and removal of serrated polyps pose a major challenge to endoscopists. Considering that precancerous serrated polyps are predominately located in the right colon could explain why interval cancers most frequently appear in the proximal colon and why colonoscopy is less protective against colon cancer in the proximal compared to the distal colon. Despite the significant impact on colorectal cancer incidence, the aetiology, incidence, prevalence, and natural history of serrated polyps is incompletely known. To effectively detect, remove, and follow-up serrated polyps, endoscopists and pathologists should be well-informed about serrated polyps. This review highlights colorectal serrated polyps in terms of biology, types, diagnosis, therapy, and follow-up.     

BRAF mutation is associated with DNA methylation in serrated polyps and cancers of the colorectum

BACKGROUND AND AIMS: Mutations in BRAF have been linked with colorectal cancers (CRC) showing high level microsatellite instability (MSI-H). However, the distribution of BRAF mutations in MSI-H cancers remains to be clarified with respect to precursor lesions and the CpG island methylator phenotype (CIMP). METHODS: Forty three hyperplastic polyps (HP), nine mixed polyps (MP), five serrated adenomas (SA), 28 conventional adenomas (AD), 18 hereditary non-polyposis colorectal cancers (HNPCC), and 127 sporadic CRC (46 MSI-H and 81 non-MSI-H) were collected from patients undergoing colectomy for either CRC or hyperplastic polyposis. Twenty five of 57 serrated lesions were derived from four patients with hyperplastic polyposis. HP were further subdivided according to recently documented morphological criteria into 27 classical HP and 16 variant lesions described as "sessile serrated adenoma" (SSA). All tumours were screened for BRAF activating mutations. RESULTS: The BRAF mutation was more frequent in SSA (75%) and MP (89%) than in classical HP (19%), SA (20%), and AD (0%) (p<0.0001), and also in sporadic MSI-H cancers (76%) compared with HNPCC (0%) and sporadic non-MSI-H cancers (9%) (p<0.0001). The BRAF mutation was identified more often in CIMP-high serrated polyps (72%) and CIMP-high CRC (77%) than in CIMP-low (30%) and CIMP-negative (13%) polyps (p = 0.002) as well as CIMP-low (18%) and CIMP-negative (0%) CRC (p<0.0001). CONCLUSIONS: The BRAF mutation was frequently seen in SSA and in sporadic MSI-H CRC, both of which were associated with DNA methylation. Sporadic MSI-H cancers may originate in SSA and not adenomas, and BRAF mutation and DNA methylation are early events in this "serrated" pathway.     

Comparison of malignant potential between serrated adenomas and traditional adenomas

BACKGROUND: Serrated adenoma is a discrete colorectal epithelial neoplastic lesion that can evolve into colorectal cancer. However, the degree of malignant potential has not been firmly established as yet. The purpose of the present paper was to compare the malignant potential and clinicopathological features between serrated and traditional adenomas. METHODS: A total of 124 serrated adenomas from 116 patients were assessed, and 419 traditional adenomas from 200 were randomly selected. The combination of nuclear dysplasia and serration of > or =20% of crypts was regarded as serrated adenoma. The clinicopathological features of serrated and traditional adenomas were compared, and multivariate analysis performed to confirm whether the malignant potential of serrated adenoma was similar to that of traditional adenoma. RESULTS: The differences in age, sex, total number of adenomas, and synchronous lesions including adenoma with high-grade dysplasia and carcinoma between subjects with and without serrated adenoma were not significant. Serrated adenomas were more frequently located in the rectum and sigmoid colon (P < 0.001), and the average size of serrated adenomas was greater than that of traditional adenomas (P < 0.05). The incidence of malignant lesions including high-grade dysplasia and carcinoma in serrated adenomas was found to be lower than in traditional adenomas (3.2% vs 9.3%, P < 0.05). In the multivariate analysis, adenoma type and polyp size constituted the risk factors for the incidence of high-grade dysplasia and carcinoma. CONCLUSIONS: Serrated adenoma is a premalignant lesion, but it has a lower potential for the development of malignancy than traditional adenomas.     

Colorectal proliferation and apoptosis in serrated versus conventional adenoma‐carcinoma pathway: growth,progression and survival

Background: Hyperplastic polyp, serrated adenoma and serrated adenocarcinoma form a morphological continuum, and are likely to be biologically related. The growth rate and malignant conversion rate of serrated adenoma are postulated to be higher than those of conventional adenoma. Methods: Immunohistochemistry for M30 and Ki67 was used to compare apoptosis and proliferation in colorectal hyperplastic polyps, serrated adenomas and serrated adenocarcinomas, and in relation to conventional adenomas and adenocarcinomas. Results: There was an abrupt increase in the apoptosis in carcinomas of serrated adenoma–serrated adenocarcinoma pathway, indicating that inhibition of apoptosis is not maintained in serrated adenocarcinomas. Proliferation was significantly lower at the invasive margin than in the central part in adenocarcinomas, particularly in serrated adenocarcinomas (P?Conclusions: Disordered regulation of apoptosis occurs later in serrated pathway than in conventional adenoma‐carcinoma pathway during malignant conversion. Serrated adenoma growth is not likely to be slower than adenoma growth, as judged by the proliferation and apoptosis rates in serrated adenomas and adenomas. In cancer, the decrease of proliferation and apoptosis in the invasive margin is likely to influence the behaviour of the tumour.