Distinction of differentiated type early gastric carcinoma with gastric type mucin expression

Abstract

BACKGROUND Intestinal and diffuse gastric carcinomas differ in morphology and growth behavior. Differentiated type gastric carcinoma (DGC), which corresponds roughly with the intestinal type of Lauren, can demonstrate phenotypic properties associated with mucin expression and brush border. However, their clinical significance is controversial. A classification based on mucin phenotype and brush border was performed to determine the clinicopathologic diversity of DGCs in their early stage. METHODS A total of 120 specimens from 116 DGC patients with definite submucosal invasion were evaluated both macroscopically and histologically. All sections were examined immunohistochemically with human gastric mucin, Muc‐2, and CD10 and with mucin histochemically with paradoxical concanavalin A staining and high iron Diamine‐Alcian Blue. They were classified into gastric type (G‐type), intestinal type (I‐type), mixed gastric and intestinal type (M‐type), or null type (N‐type) phenotypes. The immunoreactivity of E‐cadherin and β‐catenin also was investigated to determine the correlation between mucin phenotype and clinicopathologic factors. RESULTS The G‐type phenotype was found to be in contrast to I‐type: G‐type was an independent factor associated with lymph node metastasis. Significant correlations were observed between the G‐type phenotype and the complex type carcinoma found that was histologically: lymphatic invasion, lymph node metastasis, and the abnormal expression of E‐cadherin. A significant difference in the proportion of mucin phenotypes between papillary type and tubular type carcinoma was observed. G‐type was found to be the predominant phenotype in papillary carcinoma in contrast to tubular carcinoma. CONCLUSIONS The G‐type mucin phenotype and papillary adenocarcinoma should be distinguished from other types of DGCs because of their increased malignant potential in the incipient phase of invasion and metastasis. The significance of G‐type and papillary adenocarcinoma should be reflected in the treatment of patients with early stage DGCs, including endoscopic mucosal resection. Cancer 2000;89:724–32. © 2000 American Cancer Society.

Worse Prognosis in Papillary, Compared to Tubular, Early Gastric Carcinoma

“…In our cohort, papillary EGCs, compared to tubular EGCs, show significantly deeper invasion into the submucosal layer, more frequent association with a micropapillary component, and probably more frequent lymphovascular invasion, although the p value for lymphovascular invasion was 0.059. These results are parallel to those of the previous similar studies on papillary EGC from Japan 18,19 and Korea 13, in which submucosal invasion was reported to be over 20% 13, and lymphovascular invasion was found in over 28% in Korean patients 13 and over 70% in Japanese patients 18. Importantly, the nodal metastasis rate is alarmingly high and discovered in 13.6% of the current cohort and over 18% in a Korean study and 18.2% - 29.2% in two Japanese studies 18,19, which is significantly higher than that of non-papillary EGCs 13,19, including tubular EGCs as shown in this report.…”

“…Although both papillary and tubular EGC tumors are believed to be similar in prognosis and risk of nodal metastasis 6, the recent investigations from others and ours show the results otherwise 9,13,18. We demonstrated several significant differences in the present comparison study between these two groups of EGC in prognosis-associated risk factors, such as significantly older patient age, more frequent proximal gastric location, and more common association with a micropapillary component, in addition to deeper invasion and higher frequency of lymphovascular, nodal, and distant metastases, as aforementioned.…”

“…Distant metastasis is also more common in papillary than in tubular EGCs, as reported previously for papillary gastric cancer 10, although the difference in the current study did not reach a statistically significant level because of the small sample size. Given more aggressive pathobiologic behavior and higher risk of nodal and distant metastases than tubular EGCs, papillary EGCs need to be treated differently and individually 13,18.…”

Expression of immunohistochemical markers according to histological type in patients with early gastric cancer

“…Furthermore, we also performed IHC staining and extensively examined E-cadherin, b-catenin, VEGF, p53, and Ki-67 expression levels. Although previous studies have not shown consistent results in respect to mucin phenotype expression and its relationship with the histological type of gastric cancer, the available data suggest that mucin phenotype is related to invasiveness, recurrence, and prognosis [2,11,17,21,22]. Our phenotyping data suggested that TAC was associated with intestinal metaplasia [11], but that PCC was derived from gastric mucosa de novo [23].…”

“…E-cadherin maintains intercellular adhesion and is connected to b-catenin and the actin cytoskeleton. Downregulation of E-cadherin and b-catenin decreases the ability of cells to adhere to each other, which induces their detachment from the primary tumor, leading to infiltration into surrounding tissues [21,25,27,28]. Several familial gastric cancers are associated with inactivation of the E-cadherin gene causing loss of cell adhesion [29].…”