Chen Hui, Lefferts Joel A, Schwab Mary C, Suriawinata Arief A, Tsongalis Gregory J
Department of Pathology, Dartmouth-Hitchcock Medical Center and Norris Cotton Cancer Center, Lebanon, NH, USA.
Cancer Genet. 2011 May;204(5):245-51. doi: 10.1016/j.cancergen.2011.04.002.
Cetuximab is an anti-epidermal growth factor receptor that helps effectively treat patients with advanced colorectal adenocarcinoma without KRAS activating mutations. KRAS mutations are associated with 16% to 50% of isolated villous adenomas and approximately 30% of colorectal cancer. Correlation between the gross and histological subset of colorectal adenocarcinoma with KRAS mutation is unknown. Archived surgical resection specimens of colorectal adenocarcinoma (n = 42) and villous adenoma (n = 9) were collected. The gross appearance and histopathological features of these lesions were thoroughly reviewed, including the presence of a pre-existing adenomatous polyp. DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and then subjected to TaqMan real-time polymerase chain reaction to detect the seven most common KRAS mutations. KRAS mutations were found in 13 of 42 cases (31%) of colorectal adenocarcinoma and 7 of 9 cases (78%) of villous adenoma. All 13 cases of colorectal carcinoma with a KRAS mutation showed a gross polypoid configuration, compared to no KRAS mutation in the colorectal carcinomas with ulcerative configuration. In addition, 13 of 17 of these cases (76%) had histological features of adenocarcinoma with a persistent preexisting adenomatous polyp with villous architecture. In summary, grossly polypoid colorectal adenocarcinomas with a persistent pre-existing adenomatous polyp with villous architecture are strongly associated with KRAS mutations.
西妥昔单抗是一种抗表皮生长因子受体,可有效治疗无KRAS激活突变的晚期结直肠腺癌患者。KRAS突变与16%至50%的孤立性绒毛状腺瘤以及约30%的结直肠癌相关。结直肠腺癌的大体和组织学亚组与KRAS突变之间的相关性尚不清楚。收集了结直肠腺癌(n = 42)和绒毛状腺瘤(n = 9)的存档手术切除标本。对这些病变的大体外观和组织病理学特征进行了全面检查,包括是否存在先前存在的腺瘤性息肉。从福尔马林固定、石蜡包埋的组织切片中提取DNA,然后进行TaqMan实时聚合酶链反应以检测七种最常见的KRAS突变。在42例结直肠腺癌病例中有13例(31%)和9例绒毛状腺瘤病例中有7例(78%)发现了KRAS突变。所有13例具有KRAS突变的结直肠癌均表现为大体息肉样形态,而具有溃疡性形态的结直肠癌未发现KRAS突变。此外,这些病例中有17例中的13例(76%)具有腺癌的组织学特征,伴有持续存在的具有绒毛结构的腺瘤性息肉。总之,具有持续存在的具有绒毛结构的腺瘤性息肉的大体息肉样结直肠腺癌与KRAS突变密切相关。