The relationship between gastric cancer cells circulating in the blood and microsatellite instability positive gastric carcinomas

Abstract

Background: Cancers characterized by microsatellite instability may be biologically different from their counterparts with stable microsatellite sequences. Circulating cancers cell present in blood prior to surgery may constitute an adverse prognostic finding. Aim: To correlate these two phenomena with morphological features and survival in advanced gastric cancer. Methods: We examined 76 cases of resected sporadic, advanced gastric cancer by means of routine morphology and a panel of microsatellite markers. Sixty‐six cases were screened for presence of cancer cells circulating in blood prior to the surgery using combined morphological and immunocytochemical approach. Results: Twenty‐one (27.6%) cases demonstrated microsatellite instability in at least one locus. Among them 11 (14.5%) showed microsatellite instability in more than 30% (4/12) examined loci, and they were therefore designated as replication error positive (RER+). Circulating cancer cells were detected in 2/19 microsatellite instability and in 11/47 remaining cases (difference not significant). The survival of the microsatellite instability cases was significantly better. The presence of circulating cancer cells did not correlate with survival. Conclusion: It is possible that the microsatellite instability status, but not circulating cancer cells, constitutes a prognostic predictive factor in advanced gastric carcinoma. Confirmation of this hypothesis requires continuation of patient follow‐up.

Is microsatellite instability a prognostic marker in gastric cancer?: A systematic review with meta-analysis

“…Characteristics of the included studies are presented in Supplement Table SI [48], Poland (1) [44], Spain (1) [41], Australia (1) [38], Germany (1) [37], Portugal (1) [36], and the UK (1) [35]]. Only three studies [54][55][56] enrolled patients during the 21st century, and all studies analyzed patients with stage I-IV gastric cancer, with the exception of two studies (one study [35] included stage I-III, and one study [45] did not provide information on stage).…”

“…The number of markers used to estimate MSI status ranged from one to eleven, and a diversity of thresholds for assigning MSI-H or MSI was applied among the studies. Thirteen studies [7,36,37,[39][40][41]43,47,49,51,[54][55][56] used a combination of mono-and dinucleotide markers, seven [6,38,42,44,45,50,52] used only mononucleotide markers, and three [35,48,53] used only dinucleotide markers. In two studies [38,45], only one mononucleotides marker, BAT26, was used for estimating MSI status, and one study [46] considered hMLH1-negative cases MSI-H. Only four studies [49,[54][55][56] followed the National Cancer Institute (NCI) guidelines for the determination of MSI in colorectal cancer [58] (i.e., two mononucleotide markers [BAT25 and BAT26] and three dinucleotide markers [D5S346, D2S123, and D17S250]).…”

“…Median followup period was 18-92.1 months; 10 studies [35,[38][39][40][41][42]45,47,48,51] did not report follow-up duration for survival. The OS was available for 17 studies [7,[36][37][38][39][40][41][42]44,45,[47][48][49][51][52][53]56]; DSS was reported in 5 studies [6,35,43,46,50]; and DFS was estimated in 4 studies [48,[54][55][56].…”

“…Six studies [7,39,42,43,46,50] reported an adjusted HR (the HR in five studies was adjusted based on gastric cancer stages), and the log HR was extracted from raw data in two studies (one study [47] reported the raw data in the article, and it was possible to obtain the raw data from the author in one study [56]). The HR was estimated from a Kaplan-Meier curve in 14 studies [6,[35][36][37]40,41,44,45,48,49,[51][52][53][54] and from observed and expected events in two studies [38,55]. Ten studies reported that the prognosis of the MSI group was not significantly different from the non-MSI group, and 14 studies reported that the prognosis of the MSI group was better than that of others ( Supplement Table SII).…”

Allelic Imbalance of 8p Indicates Poor Survival in Gastric Cancer

“…This is in agreement with other reports published in the literature, 54,55 although some studies have found no statistical association between tumor site and MSI-H phenotypes. 50,51,56 Females were found to have MSI-H tumors more frequently than males. Most studies have not reported a gender difference associated with MSI-H status, 41,50,51,55 although the data published by Olivera and colleagues, 54 Ohmura and colleagues, 42 and Ottini and colleagues 43 seems to show a similar trend to what we have observed.…”