Gastric and Intestinal Phenotypic Marker Expression in Gastric Carcinomas and Its Prognostic Significance: Immunohistochemical Analysis of 136 Lesions

Abstract

Objective: It is well known that both gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. However, the clinicopathologic significance of these expressions has not yet been clarified. Methods: We analyzed the correlations among gastric and intestinal phenotypic marker expression patterns of the tumor, clinicopathologic findings and the patient’s outcome in 136 advanced gastric carcinomas. Results: Phenotypic marker expression was immunohistochemically evaluated using the monoclonal antibodies 45M1 (anti-human gastric mucin; HGM), CLH5 (anti-MUC6), Ccp58 (anti-MUC2) and 56C6 (anti-CD10). All tumors were classified as gastric (G), gastric and intestinal mixed (GI), intestinal (I) or unclassified (UC) phenotype. Of the 136 gastric carcinomas, 50 (36.8%), 56 (41.2%), 21 (15.4%) and 9 (6.6%) were classified as G, GI, I and UC phenotype, respectively. The G-phenotype tumors were associated with a higher rate of undifferentiated-type and infiltrative histology as compared with the I-phenotype tumors (p < 0.05 and p < 0.001, respectively). Furthermore, both univariate and multivariate analysis of survival revealed the G-phenotype tumor to be associated with a significantly poorer outcome than the I-phenotype tumor (p < 0.05). Conclusion: Our present results indicate that the gastric and intestinal phenotypic marker expression pattern of tumors, determined by the combination of HGM, MUC6, MUC2 and CD10 expression, is prognostically useful for patients with gastric carcinoma.

Characterization of the Mucin Phenotype Can Predict Gastric Cancer Recurrence After Endoscopic Mucosal Resection

“…However, some originate from gastric mucosa without intestinal metaplasia, and were named as the gastric phenotype. Some studies demonstrated that this phenotype determines a higher potential of invasion and metastasis than the intestinal type, which resulted in a worse prognosis (23,37,50,56) . Early-stage cancer, with a gastric phenotype, demonstrated aggressive biological behavior, in comparison to the undifferentiated type (50) .…”

“…Early-stage cancer, with a gastric phenotype, demonstrated aggressive biological behavior, in comparison to the undifferentiated type (50) . The mixed phenotype presented intermediate aggressiveness (23,50,56) . Encouraging results from immunohistochemical studies of gastric cancer show an increased understanding of gastric tumor carcinogenesis.…”

Differences in the histological findings, phenotypic marker expressions and genetic alterations between adenocarcinoma of the gastric cardia and distal stomach

“…In addition, our findings in this study suggest that C-Ca is more likely to transform from differentiated-into undifferentiated-type carcinomas with tumour progression. Phenotypic marker expressions and genetic alterations during carcinogenesis have been reported to differ markedly according to the histologic-type of tumours (Tajima et al, 2001b). In this study, we compared the phenotypic marker expressions and genetic alterations between differentiated-type C-Ca and differentiatedtype D-Ca, because the majority of our C-Ca cases, especially those with early-stage tumours, had differentiated-type tumours.…”

“…The phenotypic marker expression pattern has also been reported to be associated with tumour aggressiveness in gastric carcinomas. Even differentiated-type carcinomas of the G-phenotype are more likely to transform into the undifferentiated-type carcinoma and show infiltrative growth to deeper layers of the mucosa or invasion of the surrounding structures through loss of the E-cadherin gene function than tumours of the I-phenotype (Tajima et al, 2001b(Tajima et al, , 2004Yamazaki et al, 2006). Tumours exhibiting such histological transformation have been reported to show more tumour aggressiveness in terms of the invasiveness and propensity for metastasis than other histologic-type tumours (Kozuki et al, 2002).…”

“…Tumours exhibiting such histological transformation have been reported to show more tumour aggressiveness in terms of the invasiveness and propensity for metastasis than other histologic-type tumours (Kozuki et al, 2002). Furthermore, Gphenotype tumours have been reported to be significantly associated with a high risk of peritoneal recurrence and a poorer outcome after surgery as compared with tumours of other phenotypes among patients with advanced gastric carcinoma (Tajima et al, 2001b(Tajima et al, , 2004. Therefore, these previous data support our findings in this study that C-Ca predominantly showing the G-phenotype may have a greater tendency towards histological transformation and greater tumour aggressiveness than D-Ca.…”