Differentiated-type Carcinomas Research Articles

Risk Factors for Lymph Node Metastasis in Undifferentiated-Type Gastric Carcinoma.

Undifferentiated-type carcinoma has a high incidence of lymph node metastasis. The independent risk factors for lymph node metastasis in undifferentiated-type carcinoma are invasion depth, tumor size, lymphovascular invasion, and presence of ulcer. In the cases that meet the curative resection criteria, no lymph node metastasis was observed in the Japanese studies, but some metastases were observed in Korean studies. After performing curative endoscopic submucosal dissection, the survival rate is similar to that of gastrectomy. The discrepancy between endoscopy and pathology is high in undifferentiated-type carcinoma. The tumor size in endoscopy is a significant risk factor for non-curative resection, and when the tumor size is small, the non-curative resection rate is significantly reduced. Lymphovascular invasion can be assessed in pathologic examination and D2-40 stain is helpful. The presence of ulcer should be determined by pathology, but ulcer’s omission in pathology report makes the analysis difficult. Undifferentiatedtype carcinomas with differentiated-type components show higher lymph node metastasis rate than that of pure undifferentiatedtype carcinomas. The lymph node metastasis rate of signet ring cell type is lower than that of other undifferentiated-type carcinomas and is similar to differentiated-type carcinomas. The application of these additional histologic findings may improve the indication of endoscopic submucosal dissection.

Frequent microsatellite instability in papillary and solid-type, poorly differentiated adenocarcinomas of the stomach

Microsatellite instability (MSI) has been observed in 8-39 % of sporadic gastric cancers. However, despite numerous reports indicating a significant relationship between intestinal-type histology and MSI, detailed correlation between histological subtypes and MSI remains obscure. The purpose of the present study is to clarify the relationship between histological subtype and microsatellite status in gastric carcinomas. Microsatellite status was examined for 464 consecutive gastric carcinomas from 420 patients as well as histological subtypes and other clinicopathological findings. MSI was observed in 82 carcinomas (17.7 %), and the greatest proportions were observed in solid-type, poorly differentiated adenocarcinoma (43.0 %) and papillary adenocarcinoma (32.5 %), both being significantly higher than those of other subtypes. The proportion increased with advancing age (0 % at 51-64 years, 8.5 % at 65-74 years, 18.4 % at 75-84 years, 35.3 % at 85-96 years). Compared with microsatellite-stable carcinomas, microsatellite-unstable carcinomas were significantly related with older age, female gender, antral location, and predominant papillary adenocarcinoma and solid-type, poorly differentiated adenocarcinoma. Poorly differentiated type carcinoma was significantly less frequent than differentiated type in microsatellite-unstable cancer at the early stage, whereas no significant difference existed at the advanced stage. These results suggest that there are specific histological subtypes with highly frequent MSI and that gastric carcinoma with MSI originates from differentiated-type carcinomas, indicating histological diversity during tumor growth.

Mucin phenotype and narrow-band imaging with magnifying endoscopy for differentiated-type mucosal gastric cancer

Several studies have described the surface glandular structure in differentiated early gastric cancer observed by narrow-band imaging with magnifying endoscopy (NBI-ME) in two main patterns, i.e., a papillary or granular structure in an intralobular loop pattern (ILL) and a pit structure in a fine network pattern (FNP). However, it is uncertain why the NBI-ME findings of differentiated-type carcinomas are divided into two main patterns. We investigated the significance of the mucin phenotype in the morphogenetic difference between ILL and FNP. We evaluated 120 intramucosal, well- or predominantly well-differentiated tubular adenocarcinomas. In each lesion, one area that showed the predominant pattern of microsurface structures and microvessels was selected and marked by electrocoagulation for a strict comparative study by NBI-ME and pathological investigation. NBI-ME findings were classified into three patterns: ILL, FNP, and intermediate. Mucin phenotypes were judged as gastric, intestinal, or gastrointestinal type by immunohistochemistry. The mucin phenotype was gastric or gastrointestinal type in 24 (92.3%) of 26 ILL lesions. Intestinal phenotype was observed in 22 (84.6%) of 26 FNP lesions. The gastrointestinal phenotype was observed in 50 (73.5%) of 68 intermediate pattern lesions. The mucin phenotype and NBI-ME results were significantly correlated (P<0.001). The mucin phenotype of differentiated early gastric cancer might be involved in morphogenetic differences between the papillary and pit structures visualized by NBI-ME.

Gastric and Intestinal Phenotypic Marker Expression in Early Differentiated-Type Tumors of the Stomach: Clinicopathologic Significance and Genetic Background

Gastric and intestinal phenotypic cell markers are expressed in gastric carcinomas, irrespective of their histologic type. In the present study, we determined the clinicopathologic significance of phenotypic marker expression in early-stage gastric differentiated-type tumors and the association between marker expression and genetic alterations. Phenotypic marker expression was determined by examining the expressions of human gastric mucin (HGM), MUC6, MUC2, and CD10 in 63 gastric adenomas, 133 early differentiated-type carcinomas, and 24 follow-up cases with gastric adenoma. Tumors were classified into gastric, gastric and intestinal mixed, or intestinal phenotypes according to the immunopositivity of the above markers. The presence of mutations in APC, K-ras, and p53 and the microsatellite instability status were also determined in all tumors. The expressions of HGM and MUC6, representing gastric or gastric and intestinal mixed phenotypes, were significantly associated with high-grade atypia in the 63 gastric adenomas. Among the 133 early differentiated-type carcinomas, HGM expression was significantly associated with mixed-type (with an undifferentiated-type component) tumors and lymph node metastasis. MUC2 expression was inversely associated with submucosal invasion. A multivariate analysis revealed that gastric adenomas were significantly associated with the intestinal phenotype and were inversely associated with p53 mutation compared with early differentiated-type carcinomas. Among all 196 tumors, APC mutation was significantly associated with CD10 expression and the intestinal phenotype and was inversely associated with the expressions of HGM and MUC6. The microsatellite instability status was significantly associated with MUC6 expression. Malignant transformation from gastric adenoma to carcinoma was shown in 5 of the 24 follow-up cases of gastric adenoma. The malignant transformation was significantly associated with the gastric and intestinal mixed phenotype and was inversely associated with APC mutation. No malignant transformation was found in intestinal phenotype gastric adenomas with APC mutation. Our present findings show that phenotypic marker expression is associated with tumor aggressiveness during the early stage of gastric differentiated-type tumors. Differences in the biological behavior of tumors with different phenotypes may result from differences in the genetic backgrounds during the incipient phase of gastric tumorigenesis.

Gastric and intestinal phenotypic cell marker expressions in gastric differentiated-type carcinomas: association with E-cadherin expression and chromosomal changes

Gastric and intestinal phenotypic cell markers are widely expressed in gastric carcinomas, irrespective of their histological type. In the present study, the relations between the phenotypic marker expression of the tumour, histological findings, expression of cell adhesion molecules, and the chromosomal changes in gastric differentiated-type carcinomas were examined. The phenotypic marker expression of the tumour was determined by the combination of the expression of the human gastric mucin (HGM), MUC6, MUC2 and CD10, and was evaluated in comparison with the expression of cell adhesion molecules, such as E-cadherin and beta-catenin, and chromosomal changes by comparative genomic hybridization (CGH) in 34 gastric differentiated-type carcinomas. Tumours were classified into the gastric- (G-), gastric and intestinal mixed- (GI-), intestinal- (I-), or unclassified- (UC-) phenotype according to the immunopositivity of staining for HGM, MUC6, MUC2, and CD10. G-phenotype tumours were significantly associated with a higher incidence of differentiated-type tumours mixed with undifferentiated-type component, compared with GI- and I-phenotype tumours (88.9 vs 33.3%, P=0.0498 and 88.9 vs 42.9%, P=0.0397; respectively). HGM-positive tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with HGM-negative tumours (66.7 vs 21.1%, P=0.0135). GI-phenotype tumours were significantly associated with a higher incidence of tumours with abnormal expression of E-cadherin, compared with I-phenotype tumours (77.8 vs 21.4%, P=0.0131). HGM-negative tumours were significantly associated with higher frequencies of the gains of 19q13.2 and 19q13.3, compared with HGM-positive tumours (57.9 vs 20.0%, P=0.0382 and 63.2 vs 13.3%, P=0.0051; respectively). MUC6-positive tumours were significantly associated with higher frequencies of the gains of 20q13.2, compared with MUC6-negative tumours (71.4 vs 30.0%, P=0.0349). MUC2-positive tumours were significantly associated with the gain of 19p13.3, compared with MUC2-negative tumours (41.2 vs 5.9%, P=0.0391). I-phenotype tumours were significantly associated with higher frequencies of gains of 5p15.2 and 13q33-34, compared with G-phenotype tumours (66.7 vs 0%, P=0.0481, each) and also associated with higher frequencies of gain of 7p21, compared with GI-phenotype tumours (66.7 vs 0%, P=0.0481). Our present results show that gastric differentiated-type carcinomas have different characteristics according to the phenotypic marker expression of the tumour in terms of histological findings, E-cadherin expression and pattern of chromosomal changes.

Tumor differentiation phenotype in gastric differentiated-type tumors and its relation to tumor invasion and genetic alterations

To clarify the relations between tumor differentiation phenotype and tumor invasion or genetic alterations in gastric differentiated-type tumors. We examined the tumor differentiation phenotype, the presence of mutations in APC and p53, and the microsatellite instability (MSI) status in 48 gastric adenomas and 171 differentiated-type carcinomas. The tumor differentiation phenotype was determined by examining the expression of human gastric mucin (HGM), MUC6, MUC2 and CD10. The tumors were then classified into gastric- (G-), gastric and intestinal mixed- (GI-), or intestinal- (I-) phenotypes, according to the immunopositivity of the above markers. The presence of mutations in APC and p53 and the MSI status were also investigated in all the tumors. Gastric adenomas were significantly associated with CD10 expression, I-phenotype tumors and the presence of APC mutations, compared with carcinomas (66.7% vs 25.1%, P < 0.0001; 56.3% vs 14.6%, P < 0.0001; 39.6% vs 14.0%, P < 0.0001, respectively) and inversely associated with expressions of HGM and MUC6 and the presence of p53 mutations (10.4% vs 62.6%, P < 0.0001; 39.6% vs 64.3%, P = 0.003; 2.0% vs 26.3%, P = 0.001, respectively). The frequency of APC mutations was significantly higher in HGM-negative tumors, MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors than in HGM-positive tumors, MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors (32.7% vs 7.1%, P < 0.0001; 27.8% vs 14.0%, P = 0.0182; 37.3% vs 10.4%, P < 0.0001; and 38.5% vs 9.5%, P = 0.0017, respectively). The frequency of MSI was significantly higher in MUC6-positive tumors, CD10-negative tumors and G-phenotype tumors than in MUC6-negative tumors, CD10-positive tumors and I-phenotype tumors (24.8% vs 6.7%, P = 0.0009; 22.2% vs 8.0%, P = 0.0143; and 28.6% vs 9.6%, P = 0.0353, respectively). The tumor differentiation phenotype is closely related to tumor invasion and genetic alterations in gastric differentiated-type tumors.

Subcellular localization of MUC1 recognized by a monoclonal antibody MY.1E12 correlates with postsurgical prognosis in differentiated-type gastric carcinomas of stage II and III

Because of the complex nature of the diverse histologic grade in gastric carcinomas a useful biomarker should be provided to scale the aggressiveness of the disease and to determine surgical strategy, especially for advanced carcinomas. Our previous study of MUC1 in gallbladder carcinoma using mAb MY.1E12 has revealed the stromal localization of MUC1 adjacent to the carcinoma was correlated with poor prognosis. In gastric carcinoma the biological significance of the localization of MUC1 recognized by mAb MY.1E12 has not been fully investigated. We performed immunohistochemical analysis to determine the correlations with the localization of mAb MY.1E12-reactive-MUC1 (MY.1E12-MUC1) and clinicopathological findings. A total of 91 consecutive patients with stage II, IIIA or IIIB gastric carcinoma after curative resection were reviewed retrospectively. The localization of MY.1E12-MUC1 was classified as negative, apical, cytoplasmic or stromal type based on the predominant subcellular localization. Immunostaining of MY.1E12-MUC1 was recognized in 84% of the 55 cases of differentiated-type carcinoma and in 53% of the 36 cases of undifferentiated-type carcinoma (P<0.01). In differentiated-type carcinoma, the proportion of stromal-type dominant localization of MY.1E12-MUC1 was increased at the deepest invading sites. Postsurgical liver metastasis was seen in 11 (30%) of 37 cases showing stromal or cytoplasmic-type localization-dominant group and in 1 (6%) of 18 cases showing apical-type localization-dominant group or negative staining group (P<0.05). The postsurgical survival was significantly poorer in the former group than in the latter (P=0.004). In differentiated-type gastric carcinoma, the presence of the cytoplasmic- or stromal-type localization of MY.1E12-MUC1 at the deepest invading sites correlates with aggressiveness of the disease, such as the tendency to form liver metastasis. This phenotype may serve as a unique biological feature associated with the malignant behavior of differentiated-type gastric carcinomas.

Mucin Phenotype and Background Mucosa of Intramucosal Differentiated-Type Adenocarcinoma of the Stomach

Objectives: Gastric carcinomas have been divided into differentiated (intestinal) and undifferentiated (diffuse) types. Recently, classification studies based on mucin expression have revealed that some differentiated-type carcinomas are of a gastric phenotype. In this study, we investigated the clinicopathological features of differentiated-type adenocarcinomas and evaluated the background mucosa of the stomach based on mucin expression by the tumors. Methods: Seventy-six intramucosal differentiated-type adenocarcinomas of the stomach were evaluated macroscopically and histologically. The mucin expression of tumor cells was examined by immunohistochemical staining with monoclonal antibodies against human gastric mucin (45M1), class III mucin (HIK1083), small intestinal mucinous antigen (SIMA-4D3), and MUC2 (Ccp58). Tumors were classified by phenotype as gastric (G-type), intestinal (I-type), mixed (M-type), or null (N-type). Not only the clinicopathological features but also the background mucosa of the stomach of G-type and I-type carcinomas were compared histologically and serologically. Results: Seventeen tumors (22.4%) were classified as G-type, 31 (40.8%) as I-type, 22 (28.9%) as M-type, and 6 (7.9%) as N-type. The frequencies of elevated type tumors and papillary adenocarcinomas and the ratio of moderately/well-differentiated adenocarcinomas were higher in G-type than in I-type carcinomas. The scores for glandular atrophy and intestinal metaplasia were higher and the scores for chronic inflammation, polymorphonuclear neutrophil activity, and the density of Helicobacter pylori were lower in G-type than in I-type tumors. The serum level of pepsinogen I and the pepsinogen I/II ratio were significantly lower in G-type than in I-type tumors. Conclusions: G-type carcinoma is the predominant phenotype of papillary adenocarcinoma. The background mucosa of G-type carcinoma is associated with glandular atrophy and intestinal metaplasia, whereas that of I-type carcinoma is associated with active and chronic inflammation induced by H. pylori infection.

Molecular Characterization of Undifferentiated-Type Gastric Carcinoma

As the great majority of gastric cancers develop histologically differentiated, and a significant proportion of differentiated-type carcinomas progress to become undifferentiated, both histological types are likely to share several common genetic abnormalities, such as p53 mutations at advanced stages. However, a subset of gastric cancers develop as undifferentiated carcinomas, including signet-ring cell carcinoma and poorly differentiated adenocarcinoma, and the molecular pathogenesis of this tumor type remains largely unknown. To characterize the molecular features of undifferentiated-type gastric carcinomas that developed as undifferentiated-type, we examined for p53, APC, and epithelial (E)-cadherin gene mutations, microsatellite alterations including loss of heterozygosity (LOH) and microsatellite instability (MSI), and hypermethylation of the E-cadherin gene promoter in 26 early undifferentiated gastric carcinomas, consisting of 14 signet-ring cell carcinomas and 12 poorly differentiated adenocarcinomas. E-cadherin expression was evaluated immunohistochemically. p53 mutations were detected in only one poorly differentiated adenocarcinoma sample (3.8%; 1/26), whereas no APC or E-cadherin mutations were found. LOH was present only at D8S261 on the short arm of chromosome 8 in 2 of 14 (14%) informative tumors, both of which were poorly differentiated adenocarcinomas, and MSI was not observed in any of the tumors. No signet-ring cell carcinomas have been found to carry gene mutations or microsatellite alterations. In contrast, hypermethylation of the E-cadherin promoter occurred in 69% (18/26) of the tumors; 57% (8/14) of signet-ring cell carcinomas, and 83% (10/12) of poorly differentiated adenocarcinomas, and was significantly associated with loss or reduced expression of E-cadherin. Thus, whereas tumor suppressor gene mutation, LOH, and MSI were less common in undifferentiated-type early gastric carcinomas, epigenetic inactivation of E-cadherin via promoter hypermethylation may be an early critical event in the development of undifferentiated tumors.

Cellular phenotypes of differentiated-type adenocarcinomas and precancerous lesions of the stomach are dependent on the genetic pathways.

To elucidate the relationship between genetic alterations and cellular phenotypes in differentiated-type carcinomas and precancerous lesions of the stomach, mutations of p53, APC and K-ras genes were examined, as well as microsatellite instability (MSI), in 52 tumours of the stomach. Tumours were selected with the following phenotypical features, using mucin histochemical and immunohistochemical analyses, in addition to their morphological features: (1) tumours with an extremely well-preserved gastric foveolar phenotype (foveolar-type); (2) tumours with an extremely well-preserved complete-type intestinal metaplastic phenotype (CIM-type); and (3) ordinary tumours without extreme phenotypes (ordinary-type). MSI occurred in 45% of foveolar-type, 24% of ordinary-type, and 0% of CIM-type tumours. p53 gene alterations occurred in 5% of foveolar-type, 18% of ordinary-type, and 31% of CIM-type. APC gene alterations were detected in 9% of foveolar-type, 6% of ordinary-type, and 0% of CIM-type. No K-ras gene mutation was detected in any of the three types. These results indicate that the genetic pathways are quite different among the phenotypes of tumours of the stomach. The 'mutator pathway', characterized by MSI, plays an important role in the tumourigenesis of foveolar-type, but not CIM-type tumours. The 'suppressor pathway', represented by p53 alteration, could participate in the tumourigenesis of the CIM-type, but is rare in foveolar-type tumours.

The common 18-base pair deletion at codons 418-423 of the E-cadherin gene in differentiated-type adenocarcinomas and intramucosal precancerous lesions of the stomach with the features of gastric foveolar epithelium.

Alterations of the E (epithelial)-cadherin gene are often involved in undifferentiated-type carcinomas of the stomach, but not in the differentiated type. Recently, it was recognized that certain differentiated-type carcinomas possess the features of gastric foveolar epithelium. Such carcinomas are closely linked with undifferentiated-type carcinomas. Nineteen lesions (ten differentiated-type carcinomas and nine precancerous lesions) with a predominant gastric foveolar phenotype, as determined not only by mucin histochemistry and immunohistochemistry but also by morphology, were analysed for mutations of the E-cadherin gene using the nested polymerase chain reaction single-strand conformation polymorphism method. E-cadherin gene mutation was detected in 4 of 19 lesions (21 per cent) (three precancerous and one cancerous). Sequencing revealed an 18 bp deletion corresponding to codons 418-423 of exon 9 common to all four lesions. This mutation was previously reported in an advanced carcinoma of undifferentiated type. The results suggest that these tumours progress to undifferentiated-type carcinomas through loss of E-cadherin function.

A CLINICOPATHOLOGICAL STUDY OF COLORECTAL CARCINOMA WITH MUCINOUS COMPONENT

Among 562 resected cases of colorectal carcinoma, carcinomas with mucinous compenent (MC) were classified into three groups; mucinous carcinoma (MC_??_50%), 25%<MC<50%, and MC_??_25% according to mucinous area ratio on largest cross-section of the tumor. Those three groups were clinicopathologically compared with differentiated type carcinomas without MC. The ratio of threegroups were 4.8%, 5.0% and 4.4%. The incidence of lymph node metastasis and peritoneal dissemination in the mucinous carcinomas were higher than those in differentiated type and that of peritoneal dissemination in the group (25%<MC<50% was higher similarly. The five-year survival rates of mucinous carcinoma (53.3%) and the group 25%<MC<50% (48.9%) after curative resection of the advanced carcinoma were relatively lower than that of differentiated type (68.2%). The five-year survival rate (75.2%) in MC_??_25% group was almost equivalent to that of differentiated type. As to mode of recurrenca, local or peritoneal recurrence was predominantly noted in mucinous carcinomas and 25%<MC<50% carcinomas.It is throught that mucinous carcinomas tend to invade locally, and the same characteristic may be observed for colorecal carcinomas with mucinous component at moderate quantity.

Association between expression of sialosyl‐Tn antigen and intestinalization of gastric carcinomas

We examined immunohistochemically the expression of sialosyl-Tn antigen (STN) in 137 primary gastric carcinomas. In the non-neoplastic mucosa, STN was expressed in all goblet cells, most absorptive cells and Paneth cells of intestinalized tubules, whereas it was not seen in the gastric mucosa proper. We evaluated the association between the mucin-histochemical findings of intramucosal carcinomas and the STN-expression. STN was expressed in 8 of 20 undifferentiated-type carcinomas, all of which were mucin-histochemically of the gastric type. STN was expressed in 25 of 51 differentiated-type carcinomas, among which it was expressed in 3 of 12 gastric-type, 11 of 17 intestinal-type and 11 of 22 mixed-type adenocarcinomas. The extent of STN expression in the intestinal-type adenocarcinomas was significantly higher than in gastric-type adenocarcinomas and undifferentiated-type carcinomas, and that seen in mixed-type adenocarcinomas was significantly higher than in the gastric-type adenocarcinomas. We also examined STN expression in early and advanced carcinomas. As the depth of carcinoma invasion progressed, the extent of STN expression was significantly higher and its incidence was significantly higher. Our findings suggest that STN expression reflects intestinalization of the gastric mucosa, and that a kind of intestinal metaplasia occurs in progressing gastric carcinoma cells.

Time trends of early gastric carcinoma. A clinicopathologic analysis of 2846 cases.

Despite recent improvements in the diagnostic accuracy and techniques for identifying early gastric carcinoma, gastric carcinoma remains a major cause of death in the world. The clinicopathologic features of 2846 surgically resected early gastric carcinomas from 1962-1987 were reviewed, and the time trends of a variety of clinicopathologic factors were studied using both an univariate and a multivariate analysis. The differentiated type of carcinoma increased in frequency from 34-50%. The percentage of patients older than 60 years of age increased from 32-56%. The number of lesions measuring less than 3 cm increased from 28-56%. The frequency of shallow-type-IIc carcinomas measuring less than 3 cm, which had been previously difficult to detect and were mainly composed of differentiated carcinomas, increased from 46-69%. The relative proportion of the differentiated type of carcinoma was significantly higher in patients older than 60 years of age than in those younger than 60. The relative proportion of differentiated-type carcinomas measuring less than 3 cm, which had been easy to detect as opposed to undifferentiated-type carcinomas, significantly increased from 56-76%. The above time trends may indeed reflect genuine change. However, the recent increase in the rate of differentiated-type, small-sized carcinomas also suggests the possibility that such results may, in fact, be due mainly to improvements in both diagnostic accuracy and medical technology. Thus, a large number of undifferentiated-type, small-sized carcinomas might have merely failed to be found in routine gastric examination.

Histogenesis and characteristics of gastric-type adenocarcinomas in the stomach

The characteristics and histogenesis of gastric-type adenocarcinomas were studied for endoscopically removed hyperplastic polyps and intramucosal cancers found in surgically resected stomachs (m-cancers). Among 421 hyperplastic polyps, 14 differentiated-type carcinomas were found (HP-cancers). Eleven (78.6%) of these lesions were gastric-type adenocarcinomas. Out of 65 m-cancers, 22 were undifferentiated-type carcinomas and 43 were differentiated-type carcinomas, the latter being classified into 10 gastric-type adenocarcinomas (23.2%) and 13 intestinal-type adenocarcinomas: the remaining 20 were of mixed gastric and intestinal type. The mean age of the gastric-type adenocarcinoma patients did not differ from that of patients with other differentiated-type carcinomas. No appreciable signs of intestinal metaplasia wee noted in HP-cancer polyps. In m-cancers, the degree of intestinal metaplasia of the surrounding mucosa of gastric-type adenocarcinomas tended to be lower than in the other differentiated-type carcinomas, indicating a weak relationship between the histogenesis of gastric-type adenocarcinomas and intestinal metaplasia. Studies by PCNA (proliferating cell nuclear antigen) immunohistochemistry, showed that in over half of the gastric-type adenocarcinomas cases PCNA-positive cells tended to be localized within tumor tissues. In addition, point mutations of the c-Ki-ras gene were detected in 1 gastric-type adenocarcinoma and 2 intestinal-type adenocarcinomas, suggesting the occurrence of a common genetic abnormality.

LONG TERM PROGNOSIS ACCORDING TO HISTOLOGICAL TYPE OF GASTRIC CANCER

Four hundred and ninety-three resected cases of gastric cancer at the department from January 1975 to December 1987 were analyzed for clinicopathological features and prognosis by histological types of the cancers. In this study histological types of gastric cancers were classified into differentiated and undifferentiated types according to “The General Rules for the Gastric Cancer Study”. There were 246 differentiated and 247 undifferentiated cancers. In differentiated cancer group, male-to-female ratio was 2.2:1 with an average age of 63.6±10.6 years old, versus 1.3:1 with an average age of 56.5±13.5 years old in undifferentiated cancer group. Differentiated type was predominant in older (p<0.001) males (p<0.005) compared with undifferentiated type. Differentiated type carcinomas were more frequent in the distal portion of the stomach, while most undifferentiated types were seen in the middle and upper portion of the stomach (p<0.05). Severe lymphatic and venous involvement by the tumor and tumor cells penetration were noted in undifferentiated types. In each histological stage, there was no significant difference in cumulative survival curves between two histological types. However, 5-and 10-year survival rates achieved in patients with differentiated type were superior to those in patients with undifferentiated type (p<0.01). This difference in prognosis might be caused by a fact that almost half of the differentiated cancers were in stage I and most undifferentiated cancers were in an advanced stage with severe penetration.