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Revista Española de Enfermedades Digestivas

versión impresa ISSN 1130-0108

Rev. esp. enferm. dig. vol.106 no.7 Madrid jul./ago. 2014




Intestinal-type poorly differentiated gastric adenocarcinoma with microsatellite instability and defective DNA mismatch repair proteins expression

Adenocarcinoma gástrico pobremente diferenciado de tipo intestinal con inestabilidad de microsatélites y expresión defectuosa de proteínas de reparación del ADN



Alejandro Rubio-Fernández1, Mario Díaz-Delgado1, Alicia Hernández-Amate1, Tomás García-Guerrero2, María López-Macías1 and Weimar Toro-Zambrano1

Departments of 1Pathology and 2Gastroenterology. Complejo Hospitalario Universitario de Badajoz. Badajoz, Spain




DNA mismatch repair genes hMLH1, hPMS2, hMSH2 and hMSH6 are one of the multiple mechanisms human cells use to avoid defects in the cell cycle. Impaired function of these proteins via mutations or promoter hypermethylation leads to microsatellite instability (MSI).


Case report

We report a case of an 80-year-old female patient with a chronic anemia at study. A ulcerated mass in the pyloric antrum was endoscopically visualized (Fig. 1 A and B). In the resected specimen, this lesion measured 5 x 4 cm. Histolo-gically it was composed of a variable mixture of infiltrative nests and cords of atypical cells that reached the muscularis propria. There were occasionally poorly-formed glands with their lumen occupied by apoptotic cells or necrotic debris. A marked intraepithelial lymphocytosis was characteristically identified (Fig. 2A) and a peripheral inflammatory Crohn's-like response with prominent lymphoid aggregates formation (Fig. 2B). The immunohistochemical study revealed a strong expression of AE1/AE3 and CAM 5.2 cytokeratins (Fig. 2C) and focal positive staining for nuclear transcription factor CDX2 (Fig. 2D). Interestingly, expression of hMLH1 (Fig. 3A) and hPMS2 (Fig. 3B) DNA mismatch repair proteins were completely lost in tumor cells. In contrast, such cells demonstrated preserved hMSH2 (Fig. 3C) and hMSH6 (Fig. 3D) protein-expression. There were no metastases in regional lymph nodes. According to these features, the neoplasm was diagnosed as intestinal-type poorly differentiated gastric adenocarcinoma with associated MSI.






DNA mismatch repair proteins hMLH1, hPMS2, hMSH2 and hMSH6 are one of the multiple mechanisms used by human cells to avoid defects in the cell cycle. Impaired function of these proteins via mutations or promoter hypermethylation leads to microsatellite instability (MSI). This alteration has been largely studied in colorectal cancer where high levels of MSI (MSI-H) have been associated with a proximal tumor location, female gender, lower stage and a better survival stage-for-stage (1). According to this, different investigators have reported dissimilar results due to a possible survival benefit of MSI-H status in gastric adenocarcinoma (2,3). Recent studies relate such data with a more aggressive behavior on MSI-H intestinal-type gastric adenocarcinoma (4). Besides, clinical parameters like an older age, increased tumor size, distal location and lower incidence of lymph node metastasis (3), as well as histological features such as intraepithelial lymphocytes, intestinal-type, poor differentiation and tumor necrosis are likely linked with MSI-H phenotype (4). Furthermore, MSI-H gastric cancer seems to be related with the development of synchronous and multiple gastric tumors (5). In summary, further studies should be undertaken to reveal the prognostic significance of MSI-H status patients with gastric cancer. We report here a case of an 80-year-old-female with an intestinal-type poorly differentiated gastric adenocarcinoma with associated MSI with loss of hMLH1 and hPMS2 immunohistochemical expression.



1. Samowitz WS, Curtin K, Ma KN, Schaffer D, Coleman LW, Leppert M, et al. Microsatellite instability in sporadic colon cancer is associated with an improved prognosis at the population level.Cancer Epidemiol Biomarkers Prev 2001;10:917-23.         [ Links ]

2. Kim KJ, Lee TH, Cho NY, Yang HK, Kim WH, Kang GH. Differential clinicopathologic features in microsatellite-unstable gastric cancers with and without MLH1 methylation. Hum Pathol 2013;44:1055-64.         [ Links ]

3. Beghelli S, de Manzoni G, Barbi S, Tomezzoli A, Roviello F, Di Gregorio C, et al. Microsatellite instability in gastric cancer is associated with better prognosis in only stage II cancers. Surgery 2006;139:347-56.         [ Links ]

4. Kim JY, Shin NR, Kim A, Lee HJ, Park WY, Kim JY, et al. Microsatellite instability status in gastric cancer: a reappraisal of its clinical significance and relationship with mucin phenotypes. Korean J Pathol 2013;47:28-35.         [ Links ]

5. Kim SH, Ahn BK, Nam YS, Pyo JY, Oh YH, Lee Kh. Microsatellite instability is associated with the clinicopathologic features of gastric cancer in sporadic gastric cancer patients. J Gastric Cancer 2010;10:149-54.         [ Links ]

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