贲门腺癌与远端胃癌在组织学表现、表型标志物表达及基因改变方面的差异。
Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach.
作者信息
Tajima Y, Yamazaki K, Makino R, Nishino N, Masuda Y, Aoki S, Kato M, Morohara K, Kusano M
机构信息
1Division of General and Gastroenterological Surgery, Department of Surgery, Showa University, School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
出版信息
Br J Cancer. 2007 Feb 26;96(4):631-8. doi: 10.1038/sj.bjc.6603583. Epub 2007 Jan 30.
Adenocarcinoma of the gastric cardia (C-Ca) is possibly a specific subtype of gastric carcinoma. The purpose of this study was to clarify the differences in the clinicopathological characteristics between C-Ca and adenocarcinoma of the distal stomach (D-Ca), and also the differences in the expressions of gastric and intestinal phenotypic markers and genetic alterations between the two. The clinicopathological findings in 72 cases with C-Ca were examined and compared with those in 170 cases with D-Ca. The phenotypic marker expressions examined were those of human gastric mucin (HGM), MUC6, MUC2 and CD10. Furthermore, the presence of mutations in the APC, K-ras and p53 genes and the microsatellite instability status of the tumour were also determined. C-Ca was associated with a significantly higher incidence of differentiated-type tumours and lymphatic vessel invasion (LVI) as compared with D-Ca (72.2 vs 48.2%, P=0.0006 and 72.2 vs 55.3%, P=0.0232, respectively). Oesophageal invasion by the tumour beyond the oesophago-gastric junction (OGJ) was found in 56.9% of cases with C-Ca; LVI in the area of oesophageal invasion was demonstrated in 61% of these cases. Also, LVI was found more frequently in cases of C-Ca with oesophageal invasion than in those without oesophageal invasion (82.9 vs 58.1%, P=0.0197). The incidence of undifferentiated-type tumours was significantly higher in cases with advanced-stage C-Ca than in those with early-stage C-Ca (5 vs 36.5%, P=0.0076). A significantly greater frequency of HGM expression in early-stage C-Ca and significantly lower frequency of MUC2 expression in advanced-stage C-Ca was observed as compared with the corresponding values in cases of D-Ca (78.9 vs 52.2%, P=0.0402 and 51.5 vs 84.6%, P=0.0247, respectively). Mutation of the APC gene was found in only one of all cases of C-Ca, and the frequency of mutation of the APC gene was significantly lower in cases of C-Ca than in those of D-Ca (2.4 vs 20.0%, P=0.0108). The observations in this study suggest that C-Ca is a more aggressive tumour than D-Ca. The differences in biological behavior between C-Ca and D-Ca may result from the different histological findings in the wall of the OGJ and the different genetic pathways involved in the carcinogenesis.
贲门腺癌（C-Ca）可能是胃癌的一种特殊亚型。本研究的目的是阐明C-Ca与胃远端腺癌（D-Ca）在临床病理特征上的差异，以及两者在胃和肠表型标志物表达及基因改变方面的差异。对72例C-Ca患者的临床病理结果进行了检查，并与170例D-Ca患者的结果进行了比较。所检测的表型标志物表达包括人胃黏液素（HGM）、MUC6、MUC2和CD10。此外，还确定了APC、K-ras和p53基因的突变情况以及肿瘤的微卫星不稳定性状态。与D-Ca相比，C-Ca中分化型肿瘤和淋巴管侵犯（LVI）的发生率显著更高（分别为72.2%对48.2%，P = 0.0006；72.2%对55.3%，P = 0.0232）。在56.9%的C-Ca病例中发现肿瘤侵犯食管超过食管胃交界（OGJ）；在这些病例中，61%的食管侵犯区域存在LVI。此外，有食管侵犯的C-Ca病例中LVI的发生率高于无食管侵犯的病例（82.9%对58.1%，P = 0.0197）。晚期C-Ca病例中未分化型肿瘤的发生率显著高于早期C-Ca病例（5%对36.5%，P = 0.0076）。与D-Ca病例的相应值相比，观察到早期C-Ca中HGM表达频率显著更高，晚期C-Ca中MUC2表达频率显著更低（分别为78.9%对52.2%，P = 0.0402；51.5%对84.6%，P = 0.0247）。在所有C-Ca病例中仅发现1例APC基因突变，C-Ca病例中APC基因突变频率显著低于D-Ca病例（2.4%对20.0%，P = 0.0108）。本研究的观察结果表明，C-Ca是比D-Ca更具侵袭性的肿瘤。C-Ca和D-Ca之间生物学行为的差异可能源于OGJ壁不同的组织学表现以及致癌过程中涉及的不同基因途径。
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