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【资讯翻译】Sessile Serrated Adenomas: Abrupt Shift to Malignancy

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发表于 2015-10-21 11:05:50 | 显示全部楼层 |阅读模式
Sessile Serrated Adenomas: Abrupt Shift to Malignancy

Sessile serrated adenomas (SSAs) without dysplasia have a lengthy mean dwell time of 17 years before becoming dysplastic and then rapidly converting to carcinoma, according to a study published online October 15 in Gut. SSAs, prototype polyps of the serrated neoplasia pathway, are precursors to roughly 15% of colorectal cancers, but those with dysplasia or carcinoma, predominantly small flat polyps less than 10 mm in size in the proximal colon, are rarely observed.

"SSAs are subtle polyps that can be difficult to detect colonoscopically, are frequently incompletely excised and have the hypothesized potential for rapid malignant degeneration," write Mark Bettington, MD, a pathologist at the University of Queensland in Brisbane, Australia, and colleagues. Those with dysplasia or carcinoma are clinically similar to and only slightly larger than those without dysplasia, thereby making endoscopic recognition difficult.

Yet cancers of the serrated neoplasia pathway contribute disproportionately to interval colorectal carcinomas and are also associated with synchronous cancers. "Improved colonoscopic detection and removal of these lesions are likely to reduce interval cancers and understanding of the molecular drivers may allow the development of chemoprevention strategies," Dr Bettington and colleagues write.

They performed a cross-sectional analysis of 137 advanced SSAs (from 132 patients) containing regions of dysplasia/carcinoma that were prospectively collected at a community gastrointestinal pathology practice. The mean age of patients was 75.2 years, and 61.4% were women. Tumors were examined for a range of molecular characteristics, including mutations in the oncogenes BRAF and KRAS and abnormalities in the tumor suppressor genes p53 and p16, repair gene status, and the mutation-associated CpG island methylator phenotype.

Of the 137 lesions, 129 were clinically identified as polyps, and eight as carcinomas. The median polyp size was 9 mm, and 86.5% were proximal. The majority (92.7%) showed BRAF mutation, which may be an early and initiating event that directs the development of CpG island methylator phenotype, which were found in 94.0% of samples.

When compared with mismatch repair-proficient cases, mismatch repair deficiency, as indicated by loss of the mismatch repair protein MLH1 (74.5%), was associated with the following parameters: older age (76.7 vs 71.0; P < .0029), female sex (70% vs 36%; P < .0008), proximal location (91% vs 72%; P < .02), CpG island methylator phenotype (98% vs 80%; P < .02), and lack of aberrant p53 (7% vs 34%; P < .001).

A loss of p16 (43.1%) and an increase in nuclear β-catenin (55.5%), the overexpression of which is associated with tumorigenesis, were common in areas of dysplasia or carcinoma, regardless of mismatch repair status. Mismatch repair status separates these lesions into distinct clinicopathological subgroups, the authors note.

At a clinicopathological level, the most striking feature was the difference in sex distribution, with 70% of mismatch repair deficiency SSAs occurring in women compared with only 34.3% of mismatch repair-proficient cases. In addition, only 8.5% of mismatch repair deficiency cases arose in the distal colorectum compared with 28.1% of mismatch repair-proficient cases.

"These findings should be borne in mind during screening/surveillance colonoscopy," Dr Bettington and associates write.

Notably, cases with dysplasia occur in patients of similar ages to cases with carcinoma. "This, together with the rarity of these 'caught in the act' lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia," they write.

信源地址:http://www.medscape.com/viewarticle/852899

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发表于 2015-10-21 17:19:31 | 显示全部楼层
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发表于 2015-10-22 14:52:45 | 显示全部楼层
无蒂锯齿状腺瘤:突然转变为为恶性

十月十五日在线发表在《Gut》上的一项研究表明,无不典型增生的无蒂锯齿状腺瘤(SSAs)在成为异常之前有17年的较长平均停留时间,然后迅速转化为癌。SSAs,锯齿状瘤变途径的原型息肉,有大约15%的可能发展为结直肠癌。但这些不典型增生或癌,主要是结肠近端小于10mm的小扁平息肉,很少观察到。

“SSAs是细微的息肉,结肠镜下可能很难发现,经常不能完全切除,可能具有快速恶性病变的潜能,”Mark Bettington博士(澳大利亚布里斯班昆士兰大学的病理学家)及其同事们写道。具有不典型增生或癌的病例在临床上类似且仅仅略大于那些没有不典型增生的病例,从而造成内镜识别困难。

然而,锯齿状瘤变途径的癌症发展为间隔结直肠癌的比例特别高,也与同步癌症有关。“改善的结肠镜检测和去除这些病变可能减少间隔癌症,理解分子机理可能有助于化学预防策略发展,”Bettington博士及其同事们写道。

他们对137例晚期SSAs(包含不典型增生/癌区,来自132例患者)进行了代表性地分析。这些SSAs前瞻性地在胃肠病例实践组织中搜集。 患者平均年纪为75.2岁,61.4%为女性。肿瘤经过一系列的分子特征检测,包括致癌基因BRAF和KRAS突变检测、肿瘤抑制基因p53和p16异常检测、基因修复状态和突变相关的CpG岛甲基化显性。

在137例病例中,129例在临床上诊断为息肉,8例诊断为癌。息肉平均大小为9mm,且86.5%位于近端。多数(92.7%)显示BRAF突变,这可能是直接诱导CpG岛甲基化显性(94.0%的案例中都有发现)的早期和初始事件。

相较于错配修复完整的案例,由错配修复蛋白MLH1缺失(74.5%)为指示的错配修复缺陷与下列参数有关:年纪大(76.7 vs 71.0; P < .0029),女性(70% vs 36%; P < .0008),近端定位(91% vs 72%; P < .02),CpG岛甲基化表型(98% vs 80%; P < .02)和异常p53缺失(7% vs 34%; P < .001)。

不论错配修复状态如何,p16缺失(43.1%)和细胞核β-联蛋白(该基因过量表达与肿瘤发生相关)增加(55.5%)在不典型增生区或癌区是很常见的。作者指出,错配修复状态将这些机体损伤明确划分为不同临床病理学亚群。

在临床病理学水平,最显著的特征是性别上的差异,大约70%的修复错配缺陷SSAs发生在女性身上,相比之下错配修复完整的案例中女性只占34.3%。此外,只有8.5%的错配修复缺陷案例发生在结直肠末端,而错配修复完整案例中则占28.1%。

“这些发现在结肠镜检查中应当牢记在心。” Bettington博士极其同事写到。

值得注意的是,发生不典型增生的患者年龄和发生癌变的患者年龄相近。“这个情况,连同这些事实存在的罕见疾病表明,紧随长时间保持无不典型增生的SSA而来的就是快速地转变为恶性肿瘤。”他们写到。

英文原文:
Sessile Serrated Adenomas: Abrupt Shift to Malignancy

Sessile serrated adenomas (SSAs) without dysplasia have a lengthy mean dwell time of 17 years before becoming dysplastic and then rapidly converting to carcinoma, according to a study published online October 15 in Gut. SSAs, prototype polyps of the serrated neoplasia pathway, are precursors to roughly 15% of colorectal cancers, but those with dysplasia or carcinoma, predominantly small flat polyps less than 10 mm in size in the proximal colon, are rarely observed.

"SSAs are subtle polyps that can be difficult to detect colonoscopically, are frequently incompletely excised and have the hypothesized potential for rapid malignant degeneration," write Mark Bettington, MD, a pathologist at the University of Queensland in Brisbane, Australia, and colleagues. Those with dysplasia or carcinoma are clinically similar to and only slightly larger than those without dysplasia, thereby making endoscopic recognition difficult.

Yet cancers of the serrated neoplasia pathway contribute disproportionately to interval colorectal carcinomas and are also associated with synchronous cancers. "Improved colonoscopic detection and removal of these lesions are likely to reduce interval cancers and understanding of the molecular drivers may allow the development of chemoprevention strategies," Dr Bettington and colleagues write.

They performed a cross-sectional analysis of 137 advanced SSAs (from 132 patients) containing regions of dysplasia/carcinoma that were prospectively collected at a community gastrointestinal pathology practice. The mean age of patients was 75.2 years, and 61.4% were women. Tumors were examined for a range of molecular characteristics, including mutations in the oncogenes BRAF and KRAS and abnormalities in the tumor suppressor genes p53 and p16, repair gene status, and the mutation-associated CpG island methylator phenotype.

Of the 137 lesions, 129 were clinically identified as polyps, and eight as carcinomas. The median polyp size was 9 mm, and 86.5% were proximal. The majority (92.7%) showed BRAF mutation, which may be an early and initiating event that directs the development of CpG island methylator phenotype, which were found in 94.0% of samples.

When compared with mismatch repair-proficient cases, mismatch repair deficiency, as indicated by loss of the mismatch repair protein MLH1 (74.5%), was associated with the following parameters: older age (76.7 vs 71.0; P < .0029), female sex (70% vs 36%; P < .0008), proximal location (91% vs 72%; P < .02), CpG island methylator phenotype (98% vs 80%; P < .02), and lack of aberrant p53 (7% vs 34%; P < .001).

A loss of p16 (43.1%) and an increase in nuclear β-catenin (55.5%), the overexpression of which is associated with tumorigenesis, were common in areas of dysplasia or carcinoma, regardless of mismatch repair status. Mismatch repair status separates these lesions into distinct clinicopathological subgroups, the authors note.

At a clinicopathological level, the most striking feature was the difference in sex distribution, with 70% of mismatch repair deficiency SSAs occurring in women compared with only 34.3% of mismatch repair-proficient cases. In addition, only 8.5% of mismatch repair deficiency cases arose in the distal colorectum compared with 28.1% of mismatch repair-proficient cases.

"These findings should be borne in mind during screening/surveillance colonoscopy," Dr Bettington and associates write.

Notably, cases with dysplasia occur in patients of similar ages to cases with carcinoma. "This, together with the rarity of these 'caught in the act' lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia," they write.


信源地址:http://www.medscape.com/viewarticle/852899

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 楼主| 发表于 2015-10-23 15:25:50 | 显示全部楼层
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