胃髓样癌的临床病理特征和分子遗传学改变

Gastric medullary carcinoma with distinct clinicopathological features and molecular alterations

目的 探讨胃髓样癌的临床病理和分子遗传学特征。方法 17例胃髓样癌和 6 4例非髓样癌 (低级别癌 19例 ,高级别癌 4 5例 )进行临床病理、免疫组织化学染色和微卫星不稳定性的比较研究。结果 胃髓样癌病理学以瘤细胞实体样排列和纤维少、富于淋巴细胞的间质为特征。与非髓样癌比较 ,还有以下特征 :(1)胃髓样癌、低级别癌平均生存时间好于高级别癌 ,差别有统计学意义 (P =0 0 0 4 )。 (2 )胃髓样癌 2 9 4 % (5 / 17例 )、非髓样癌 9 4 % (6 / 6 4例 )未累及浆膜 ,髓样癌较不易累犯浆膜 (P <0 0 5 ) ;髓样癌、非髓样癌各 70 5 % (12 / 17例 )和 2 0 8% (11/ 6 4例 )为推进性生长 ,髓样癌推进性生长较常见 (P =0 )。(3)胃髓样癌上皮内淋巴细胞中位数为 2 380 / 10HPF ,较非髓样癌 (14 7/ 10HPF)明显 (P =0 ) ;35 2 % (6 / 17例 )髓样癌、3 1%(2 / 17例 )非髓样癌瘤周淋巴细胞阳性 ,髓样癌瘤周淋巴细胞阳性较常见 (P =0 0 0 1) ;70 6 % (12 / 17例 )髓样癌Crohn样反应阳性 ,较非髓样癌 32 8% (2 1/ 6 4例 )常见 (P <0 0 5 )。 (4 )与低级别癌比较 ,胃髓样癌和高级别癌上皮钙粘素低表达更常见 (P<0 0 5 )。 (5 ) 4 1 2 % (7/ 17例 )胃髓样癌复制误差阳性 ,比非髓样癌的 2 5 % (1/ 6 4例 )

Purpose To detect the clinicopathological and molecular features of gastric medullary cancer. Methods Seventeen medullary and 64 non-medullary gastric cancers (19 low-grade and 45 high-grade cancers) were selected. A comparative study was carried out including clinicopathological features, immunohistochemical staining and microsatellite instability analysis. Results In addition to characteristic histopathology of solid pattern and little fibrous but rich lymphoid stroma, gastric medullary cancers had prominent features as listed below, compared with those of non-medullary cancers: (1) The average survival time was found longer in medullary and low-grade cancers than that in high-grade cancers (P=0.004). (2) Cancers whithout serosa involvement were more common in medullary cancers (29.4%, 5/17) than that in non-medullary (9.4%, 6/64) (P<0.05). However, medullary cancers were more commonly associated with pushing borders (70.5%, 12/17 versus 20.8%, 11/64) (P=0). (3) The presence of intraepithelial lymphocytes (IEL ) in medullary cancers (2 380/10HPF) was more obvious than in non-medullary cancers (147/10 HPF) (P=0). Peri-tumoral infiltrating lymphocytes (pTIL) or Crohn-like reaction were present in 35.2% (5/17) or 70.6% (12/64) medullary cancers, respectively. Compared to pTIL (3.1%, 2/17)and Crohn-like reaction (32.8%, 21/64) in non-medullary cancers, both were more common in medullary cancers (P<0.05). (4) Medullary and high-grade cancers had more cases with reduced ECD expression, compared with that in low-grade cancers (P<0.05). (5) RER+ rate was more common in medullary cancers (41.2%, 7/17) than in non-medullary cancers (2.5%, 1/17) (P=0). Conclusions Gastric medullary cancer can be regarded as a unique type of gastric cancer because of its distinct clinicopathological features and genetic alterations. Two subtypes of gastric medullary cancers, RER+ and RER-, are identified. This classification may imply survival difference. Thus, analysis of Bat26 loci in gastric medullary cancer is important in the assessment of clinical prognosis.