Prognostic implications of microsatellite genotypes in gastric carcinoma

Choi, Sae Kyung; Choi, Jung‐Min; Chung, Yeun‐Jun; Kim, Kyoung‐Mee; Rhyu, Mun-Gan

doi:10.1002/1097-0215(20000720)89:4<378::aid-ijc10>3.0.co;2-t

Cited by 58 publications

(66 citation statements)

References 26 publications

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“…52,53,55,61 Moreover, MSI-H tumors are thought to be of a less aggressive nature, possibly accounting for their presentation at a lower stage and better survival rate. 41,44,50,53,55 A subclone existing within a tumor that has not lost its MMR function might be more aggressive and exhibit clonal dominance regarding growth within the murine environment compared to MMR-deficient clones. Overall, our results, in agreement with others in the literature, demonstrate xenografted tumors to be very reliable in exhibiting global molecular alterations consistent with the primary tumor that might otherwise go undetected because of normal stromal content.…”

Section: Discussionmentioning

confidence: 99%

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

French

Petroni

Thibideau

et al. 2004

The Journal of Molecular Diagnostics

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Gastric cancer is a common tumor worldwide and a tremendous health burden. However, the underlying mechanisms of tumorigenesis in this cancer's development are primarily undefined. Allelic imbalance (AI) of 8p has been reported in many cancers, yet, the target(s) of alteration and the importance of allelic imbalance on this chromosomal arm in gastric carcinoma development remained to be characterized. Our findings confirmed a high rate of AI on 8p in gastric cancers. Moreover, we demonstrated that AI on 8p, either overall or at marker D8S560, was associated with poorer survival in patients with gastric cancer. Finally, gastric cancers with a high rate of microsatellite instability were significantly associated with noncardia tumors and with female gender.

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Section: Discussionmentioning

confidence: 99%

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

French

Petroni

Thibideau

et al. 2004

The Journal of Molecular Diagnostics

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“…Recently, specific LOH patterns have been implicated as predictors of poor survival in various solid tumours (Choi et al, 2000;Hirano et al, 2001;Choi et al, 2002;Rosin et al, 2002;Nakayama et al, 2003b). In the current study, of the 116 markers examined only 19q12 and Xq11 -12 showed significant correlation between postoperative progression-free survival time and LOH status (Table 3).…”

Section: Discussionmentioning

confidence: 99%

Allelic loss at 19q12 and Xq11–12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential

et al. 2004

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Ovarian tumours of low malignant potential (LMP) are intermediate between adenomas and ovarian carcinomas. These tumours are often associated with a significantly better prognosis than ovarian carcinomas. However, a subset of these tumours can progress and become lethal. In order to seek sensitive diagnostic tools for monitoring patients after surgical operation, we performed a genomewide scan for loss of heterozygosity (LOH) in 41 mucinous LMPs using 91 polymorphic microsatellite markers at an average interval of 50 cM across all of the human chromosomes and 25 LOH markers reportedly associated with ovarian carcinoma. In addition, we assessed whether clinicopathological parameters, microvessel density, Ki-67 labeling index, apoptotic index or p53 overexpression would be useful for predicting the postoperative outcome of LMP patients. Of the 116 markers examined, 19q12 and Xq11 -12 showed significant correlation between postoperative progression-free survival time and LOH status (Po0.05). Patients with a high Ki-67 labeling index had a significantly poorer progression-free survival time than those with lower levels (P ¼ 0.042). Other clinicopathological factors and immunohistochemical analysis had no correlation with progression-free survival time in this series of patients. When the combination of LOH at 19q12 and/or Xq11 -12 was assessed using Cox's regression analysis, patients with tumours that showed LOH at these positions were at greatest risk of progression (P ¼ 0.0073). These findings suggest that the identification of LOH at 19q12 and/or Xq11 -12 in former mucinous LMP sites should alert the clinician to the presence of a potentially aggressive lesion in the coelomic epithelium, even if a distinction between second primary tumours or recurrence could not be determined.

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“…6,16,17 Many studies have demonstrated that LOH is fairly common in intestinal type gastric cancer but rare in diffuse type tumors. 3,6,8,10,12,17 These findings suggest that diffuse type tumor is a separate entity from intestinal gastric carcinoma with its own initiation and progression mechanisms. The Japanese classification of gastric adenocarcinoma divides poorly differentiated adenocarcinomas into solid-type and non-solid-type subgroups.…”

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confidence: 92%

“…3,4 To date, several studies have attempted to investigate the relationship between various clinicopathological characteristics or outcomes and LOH status in gastric carcinoma. [5][6][7][8][9][10][11][12][13][14][15] However, these studies substantially disagree among themselves with regard to the frequency of LOH, and the relationships between LOH and various clinicopathological factors or outcomes remain controversial. Some of these studies have focused on the relationship between clinicopathological factors and the extent of chromosomal loss (fractional allelic loss (FAL)).…”

mentioning

confidence: 99%

“…Some of these studies have focused on the relationship between clinicopathological factors and the extent of chromosomal loss (fractional allelic loss (FAL)). 9,10,13,14 Most studies investigating the relationship between single chromosomal loss and clinicopathological variables have only evaluated tumor stage (depth of invasion). 5,6,8,11 Therefore, the clinicopathological significance of LOH, especially single chromosomal region loss, with respect to the initiation and progression of gastric carcinoma remains poorly understood.…”

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confidence: 99%

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Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique

et al. 2006

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The clinicopathological significance of loss of heterozygosity (LOH) in gastric carcinoma remains poorly understood. We and other researchers have previously demonstrated that LOH is fairly common in intestinaland solid-type gastric carcinomas, but rare in diffuse-type tumors. In this study, we investigated the relationship between clinicopathological variables and LOH status in intestinal-and solid-type gastric carcinomas. The crypt isolation technique was utilized to analyze LOH at 1p36, 3p14, 4p15, 5q21-22, 8p11-12, 9p21, 13q22, 17p13.1 18q21 and 22q13.31 in 113 intestinal-and solid-type gastric carcinomas using a polymerase chain reaction assay. Immunostaining with D2-40 and Elastica van Gieson staining were used to detect lymphatic invasion and vessel invasion, respectively. High LOH rates (49-71%) were observed in all chromosomal regions tested. 1p36 loss was significantly associated with advanced tumors and lymph node metastasis. 8p11-12 loss was significantly associated with lymph node metastasis, lymphatic invasion, and vessel invasion. 17p13.1 (TP53) loss was significantly associated with vessel invasion. 22q13.31 loss was significantly associated with advanced tumors, lymph node metastasis, lymphatic invasion, vessel invasion and late TNM stage. No significant associations were observed between LOH at other chromosomal regions and aggressive behaviors. In addition, significantly higher LOH rates at 1p36, 9p21, 18q21 and 22q13.31 were observed in cardiac tumors compared with noncardiac tumors. These results suggest that in intestinal-and solid-type gastric carcinomas, LOH on 3p14, 4p15, 5q21-22, 9p21, 13q22 and 18q21 is associated with carcinogenesis, while LOH on 1p36, 8p11-12, 17p31.1 and 22q13.31 is associated with tumor progression.

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Prognostic implications of microsatellite genotypes in gastric carcinoma

Cited by 58 publications

References 26 publications

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

Allelic loss at 19q12 and Xq11–12 predict an adverse clinical outcome in patients with mucinous ovarian tumours of low malignant potential

Clinicopathological significance of loss of heterozygosity in intestinal- and solid-type gastric carcinomas: a comprehensive study using the crypt isolation technique

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