Hughes N R, Bhathal P S
Department of Anatomical Pathology, Royal Melbourne Hospital, Parkville, Victoria, Australia.
J Clin Pathol. 1997 Sep;50(9):741-8. doi: 10.1136/jcp.50.9.741.
To investigate the phenotype of cells comprising diffuse and intestinal-type gastric cancers using monoclonal antibodies to two antigens. One antigen (designated D10) is characteristic of gastric mucous neck cells, cardiac glands, pyloric glands, and Brunner's glands. The second antigen (designated 17NM) is specific to the mucous vacuole of intestinal goblet cells.
Thirty two gastrectomy specimens with adenocarcinoma were studied. Serial paraffin sections were stained immunohistochemically for D10 and 17NM and histochemically for acid and neutral mucins. The cancers were classified histologically as of either diffuse or intestinal type according to Lauren.
Of 15 diffuse-type gastric carcinomas, 11 showed the majority of cancer cells staining for D10 while four were typical signet ring cell cancers staining predominantly for 17NM; five tumours displayed both phenotypes with the two phenotypes segregated in different areas of the tumours. In contrast, of 16 intestinal-type cancers, six expressed 17NM, three D10, five neither antigen, and two expressed both antigens. One indeterminate-type cancer expressed both antigens. The staining of individual cells for D10 and 17NM was mutually exclusive in both diffuse and intestinal types. In contrast to the diffuse cancers, intestinal-type cancers typically expressed either antigen only in occasional small groups of cells and individual cells.
In disease, the gastric stem cell can assume the capacity of the duodenal stem cell for divergent differentiation into either intestinal goblet cells (for example, as in intestinal metaplasia) or Brunner's gland cells (for example, as in pyloric gland/Brunner's gland metaplasia). With neoplastic transformation, this potential for divergent differentiation is maintained and gives rise to diffuse-type cancers that display either the D10 phenotype, the 17NM phenotype, or the clonal expression of both phenotypes. In the more cell cohesive (intestinal-type) tumours, differentiation for antigen expression is poorly developed and more frequently directed towards the intestinal goblet cell phenotype.
使用针对两种抗原的单克隆抗体研究弥漫型和肠型胃癌细胞的表型。一种抗原(命名为D10)是胃黏液颈细胞、贲门腺、幽门腺和十二指肠腺的特征性抗原。第二种抗原(命名为17NM)是肠杯状细胞黏液泡所特有的。
研究了32例腺癌胃切除标本。对连续石蜡切片进行D10和17NM免疫组织化学染色以及酸性和中性黏液组织化学染色。根据劳伦分类法,将癌症组织学分类为弥漫型或肠型。
在15例弥漫型胃癌中,11例显示大多数癌细胞对D10染色,4例为典型印戒细胞癌,主要对17NM染色;5例肿瘤表现出两种表型,且两种表型在肿瘤的不同区域分离。相比之下,在16例肠型癌中,6例表达17NM,3例表达D10,5例既不表达这两种抗原,2例表达两种抗原。1例未定型癌表达两种抗原。在弥漫型和肠型中,单个细胞对D10和17NM的染色相互排斥。与弥漫型癌不同,肠型癌通常仅在偶尔的小细胞群和单个细胞中表达其中一种抗原。
在疾病状态下,胃干细胞可具备十二指肠干细胞的能力,分化为肠杯状细胞(如在肠化生中)或十二指肠腺细胞(如在幽门腺/十二指肠腺化生中)。随着肿瘤转化,这种分化潜能得以保留,并导致弥漫型癌症表现出D10表型、17NM表型或两种表型的克隆性表达。在细胞黏附性更强的(肠型)肿瘤中,抗原表达的分化发育不良,更常趋向于肠杯状细胞表型。