Endocardial Invasion of Lung Cancer Undiagnosable before Autopsy.

A 59-year-old male patient presented with left chest discomfort on admission. His medical history included encephalitis in childhood and his smoking history was 20 cigarettes per day for 40 years. A physical examination showed an anemic and edematous face with weak respiratory sounds in the left lung. The patient had elevated calcium levels and decreased hemoglobin and potassium. His parathyroid hormone-related protein level was elevated. Thoracic radiography showed cardiomegaly and computed tomography revealed a left lung mass with invasion of the heart and pleural effusion. Magnetic resonance imaging showed endocardial invasion of the tumor mass. Gallium-68 imaging revealed positive accumulation in the region surrounding the heart. No diagnoses were possible upon frequent cytology of his sputum and pleural effusion. The patient died from congestive heart failure with anoxia 38 days after admission. An autopsy revealed tumoral mass occlusion in the left main bronchus and tumoral invasion of the left atrium, left ventricle, and aorta.

Spontaneous remission of epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly.

A 94-year-old female patient presented with anorexia and left axillar lymphadenopathy on admission. Her past history was angina pectoris at 83 years of age and total gastrectomy due to gastric cancer at 87 years. The family history revealed that her son had had a malignant lymphoma, the histopathological diagnosis of which was diffuse large B-cell lymphoma. A physical examination showed both cervical, axillar, and inguinal lymphadenopathy without tenderness. She had elevated lactate dehydrogenase, ferritin, and soluble interleukin-2 receptor (sIL-2R). Whole-body computed tomography confirmed the cervical, axillary, and inguinal lymphadenopathy. Gallium-68 imaging revealed positive accumulation in these superficial lymph nodes. A right inguinal lymph node biopsy showed features of Epstein-Barr virus-associated lymphoproliferative disorder. Immunohistological studies on this lymph node biopsy showed CD20-positive large cells, CD3-positive small cells, and CD30-partly-positive large cells. In situ hybridization showed Epstein-Barr virus-positive, LMP-partly-positive, and EBNA2-negative cells. She refused chemotherapy as her son had died from hematemesis during chemotherapy. She received intravenous hyperalimentation for 1 month after admission. No palpable lymph nodes were identified by physical examination or computed tomography 3 months after admission, and regression of lactate dehydrogenase, ferritin, and sIL-2R was observed. She recovered from anorexia and was discharged. She died from pneumonia 10 months later after initial symptoms of anorexia. The autopsy showed no superficial lymphadenopathy.

Significance of integrin alpha2/beta1 in peritoneal dissemination of a human gastric cancer xenograft model.

In the present study, the role of integrin alpha2/beta1 in peritoneal dissemination of gastric cancer was investigated using an in vivo xenograft model for the highly metastatic MKN-45-P gastric cancer cells. Metastatic ability of MKN-45-P cells was significantly associated with the simultaneous expression of integrin alpha2 and alpha3 subunits. In an in vitro adhesion assay, neutralizing antibody for integrin alpha2 or beta1 subunit inhibited the adhesion of MKN-45-P cells to collagen type I and type IV. Moreover, the injection of anti-beta1 monoclonal antibody reduced the number of cancer cells on the peritoneum in nude mice that had been inoculated with MKN-45-P cells. These results suggest that integrin alpha2/beta1 represents a candidate target molecule available for the prevention of gastric cancer peritoneal dissemination.

Postoperative results of left upper abdominal evisceration for advanced gastric cancer.

BACKGROUND/AIMS: In spite of the improvement of surgical techniques, the prognosis of patients with advanced gastric cancer still remains poor. With the aim of achieving en bloc resection of primary tumor, peritoneal dissemination on the greater omentum and lymph node metastasis, left upper abdominal evisceration (LUAE) was performed for 75 patients. In this report, we investigated the prognostic difference between the LUAE group and standard gastrectomy (total gastrectomy + pancreatosplenectomy). METHODOLOGY: In the LUAE group, total gastrectomy was performed with the en bloc resection of the transverse colon, pancreas body and tail, spleen and left adrenal gland. In addition, omental bursa, covering retroperitoneum and pancreas body and tail was resected in combination with greater omentum, transverse mesocolon, and lesser omentum. RESULTS: There were 3 (4.1%) postoperative death in the LUAE group, and 2 (1.7%) in the control group. However, there was no statistical difference in the incidence of postoperative complications between these 2 groups. The overall 5-year survival rates of the LUAE and control groups were 33% and 39%, respectively. There was no statistical survival difference between these 2 groups. Survival difference between the LUAE and control group was not found in terms of tumor location, wall invasion, lymph node status, peritoneal dissemination, and macroscopic type. CONCLUSIONS: From these results, LUAE cannot improve the survival of patients with advanced gastric cancer. Consequently, LUAE should be indicated for T4 tumors, which directly invade into the transverse colon.

Esophageal sarcomas: report of three cases.

BACKGROUND/AIMS: Sarcomas of the esophagus, including carcinosarcoma, are rare neoplasms. METHODS: The clinical and pathologic characteristics of 3 patients with esophageal sarcomas are presented, including the only recorded esophageal carcinosarcoma and 2 patients with leiomyosarcoma. RESULTS: All 3 patients were males who presented with dysphagia or an abnormal shadow of the mediastinum on a plain chest X-ray. Two tumors were in the middle esophagus, and the remaining one was in the distal esophagus. On endoscopic examination, all three tumors were noted to be polypoid. These patients underwent surgical excision. One patient died 7 days following the operation, and the remaining 2 patients died of liver metastasis 10 and 22 months following the treatment. CONCLUSION: Esophagectomy or esophagogastrectomy is a surgical choice. Even if metastases are present, a palliative resection can still be performed.

Chemohyperthermic peritoneal perfusion for peritoneal dissemination in various intra-abdominal malignancies.

A total of 25 patients with severe peritoneal dissemination underwent chemohyperthermic peritoneal perfusion (CHPP). The primary tumors in these patients comprised colorectal cancer (n = 14), ovarian cancer (n = 6), cervical cancer, (n = 1), small bowel cancer (n = 1), pseudomyxoma retroperitonei (n = 1), cystoadenocarcinoma of liver (n = 1), and pancreas cancer (n = 1). The intraperitoneal perfusion was carried out with a magnet pump for 60 min. The heated perfusate contained anticancer drugs to act synergistically with the hyperthermia. The intraperitoneal temperature was maintained at 42.0-42.5 degrees C. Eight of 25 patients showed CR, four PR, ten NC, and three PD, and the percentage (CR+PR) representing the overall efficacy rate was 48.0%. The morbidity rate was 8% (2/25) and there was no treatment-associated mortality. The percentage (CR+PR) of the patients with colorectal cancer was 57%; ovarian cancer, 50%; and other malignancies, 20%. The 1 year-and 3 year-survival rates of all the patients were 55% and 26%, respectively. The median survival periods of the CR, PR, NC, and PD groups were 4.0, 1.0, 1.0, and 0.7 years, respectively. The survival curve of the CR group was the best of all the groups (P = 0.02). These results indicated that CHPP was a feasible therapy and exerted a direct anticancer effect on peritoneal dissemination especially in the case of ovarian cancer, and the prognosis of complete responders was improved.

Smooth muscle tumors of the esophagus: clinicopathological findings in six patients.

Preoperatively, it is difficult to discriminate leiomyoma and leiomyosarcoma of the esophagus, which are rare smooth muscle tumors. The objective of this study was to evaluate the clinicopathological findings of this unusual lesion. A search of the surgery archives of the Toyama Prefectural Central Hospital of Pathology revealed six cases of esophageal smooth muscle tumors. Clinicopathological findings were reviewed retrospectively. Only three patients (50%) presented with dysphagia, and the remaining three patients were asymptomatic. These patients underwent surgical excision. Histologically four of the six tumors were leiomyomas, and the other two tumors were leiomyosarcomas. Two tumors were in the upper to middle esophagus, and the remaining four were in the distal esophagus. On endoscopic examination, all tumors were noted to be polypoid. The two leiomyosarcomas measured over 5 cm and the four leiomyomas less than 4 cm. Neither ulceration nor necrosis proved to be of use in discriminating leiomyoma and leiomyosarcoma. The two patients with leiomyosarcoma died of liver metastasis 10 and 22 months after the treatment. Patients with leiomyosarcoma presented with distant metastasis and/or recurrence, with hematogeneous metastasis being the predominant type of recurrence.

[The expression of cMET/hepatocyte growth factor receptor in colorectal cancer].

In this study, we estimated the expression of c-MET/Hepatocyte Growth Factor receptor in colorectal cancers by immunohistochemistry. In 118 patients, c-MET wee expressed in 65 patients (55%). About the clinicopathological findings of metastasis, the proportion of c-MET-positive in the patients with liver metastasis, 78% (18/23), was significantly higher than that without liver metastasis, 49% (47/95), but there was no significant difference about lymph node metastasis and peritoneal dissemination. About the pathological findings of primary lesion, the proportion of c-MET-positive in the patients with infiltration into lymphatic vessels, 63% (48/76), was significantly higher than that without infiltration, 40% (17/42), but there was no significant difference about infiltration into veins. The proportion of c-MET-positive increased as the tumor stage proceeded from t1 to t4 and as the histopathological stage proceeded from I to IV. These results suggest that c-MET may play an important role in the growth and scattering of colorectal cancer cells.

The relation between the growth patterns of gastric carcinoma and the expression of hepatocyte growth factor receptor (c-met), autocrine motility factor receptor, and urokinase-type plasminogen activator receptor.

BACKGROUND: Hepatocyte growth factor receptor (c-met), autocrine motility factor receptor (AMFR), and urokinase-type plasminogen activator receptor (uPAR) are known to play important roles in tumor cell migration, invasion, and metastasis. The authors studied the relation between the expression patterns of these genes and the growth patterns of human gastric carcinoma. METHODS: The relation between the expression of c-met, AMFR, and uPAR and clinicopathologic parameters was studied using immunohistochemical preparations from 102 paraffin embedded primary gastric carcinomas. RESULTS: Of 102 cases, 43 (42%) had overexpression of c-met, and AMFR and uPAR immunoreactivity was observed in 41 cases (40%) and 38 cases (37%), respectively. Macroscopic examination revealed that all three genes were expressed in 1 (3%) of 32 early stage gastric carcinomas, 0 (0%) of 29 localized carcinomas (Borrmann types 1 and 2), and 16 (39%) of 41 infiltrating carcinomas (Borrmann types 3 and 4). In particular, the incidence (68%, 13 of 19 cases) of simultaneous expression of the three genes was significantly higher in Borrmann type 4 gastric carcinoma than in the other macroscopic types (P < 0.01). The overexpression of these genes was also closely associated with lymph node metastasis and peritoneal dissemination. In addition, the simultaneous overexpression of the three genes was associated with positive lymphatic vessel invasion and infiltrating type. Patients with tumors that simultaneously expressed all three genes had significantly poorer prognoses than those with tumors expressing only one or two of the genes. Furthermore, the number of genes expressed was closely related to the prognosis, and the Cox proportional hazards model identified this as one of the independent prognostic factors. CONCLUSIONS: These results suggest that the expression patterns of c-met, AMFR, and uPAR may be closely associated with the progression and invasion of gastric carcinoma as well as the prognoses of the patients. Borrmann type 4 gastric carcinoma is characterized by the diverse and simultaneous expression of these three genes.

The time interval between primary colorectal carcinoma resection to occurrence of liver metastases is the most important factor for hepatic resection. Analysis of total course following primary resection of colorectal cancer.

The lack of any other effective treatment for colorectal liver metastases makes hepatic resection a primary treatment consideration. Between January 1980 and December 1996, 36 patients with metachronous liver metastases who underwent hepatic resection were reviewed. The age, sex, site of primary lesion, stage, size and number of hepatic metastases, and time interval between primary colorectal carcinoma resection to occurrence of liver metastases (disease-free interval, DFI) were documented. DFI was 569 days on average. Complete removal of primary colorectal cancer and metastatic liver tumour with histologically negative resection margins was accomplished in all cases. The 5 year survival rate following the first operation for primary colorectal cancer was 43.1%. The length of DFI influenced, independently, patients' prognoses based upon not only univariate but also multivariate survival analysis (P<0.01). We conclude that the DFI is the independent prognostic factor for metachronous liver metastases after curative resection of primary tumour.

[Alteration of p15 and p16 gene in gastric cancer].

We analyzed p15 and p16 gene alterations in gastric cancer. Only MKN45 showed both homozygous deletions but other cell lines and all of tumor specimens did not show any alterations. Using RT-PCR analysis, decreased or no expression of the p16 gene was found in 1 of 7 cell lines (except MKN45) (14.2%) and in 8 of 20 tumors (40%), whereas no abnormalities of p15 gene expression were found. These results suggest that the p16 gene may correlate with tumorigenesis and tumor expansion due to decrease or loss of gene products in gastric cancer.

Early diagnosis of mucosal squamous cell carcinoma of the esophagus: including two interesting cases of superficial spreading-type and multicentric-type squamous cell carcinomas.

We reviewed 10 patients with esophageal mucosal carcinoma in order to improve the early diagnosis of the disease. Histologically seven of the 14 lesions were carcinomas in situ (epithelial cancer), and the other seven lesions were carcinomas confined to the mucosa other than epithelial cancer (muscularis mucosae cancer), all 14 lesions were squamous cell carcinomas (SCC). One of these seven mucosal SCC, which demonstrated an extensive spreading-type SCC in which the size of the SCC was 7 cm long while extending entirely around the esophageal lumen in circumferential spread, is described in detail, and multiple epithelial cancers existed separately in one case. Eleven lesions diagnosed before operation showed abnormal findings on conventional endoscopy regardless of the size and depth of transmural invasion. An additional lesion was visible with dye endoscopy as an unstained area, but it was not visible with radiography or conventional endoscopy. Dye endoscopy using Lugol solution is very important because it allows detection and evaluation of the extent of esophageal mucosal cancer.

Correlation of peritoneal dissemination and integrin alpha 3 expression in gastric cancer.

To clarify the interrelationship between alpha 3 integrin, subunit/E-cadherin expression and peritoneal dissemination in gastric cancer, alpha 3 integrin subunit and E-cadherin expression gas were immunohistochemically examined and were correlated with clinicopathologic parameters. Among 150 primary gastric cancers, alpha 3 integrin subunit and E-cadherin were strongly expressed in 96 (65%) and 88 (59%) tumors, respectively. Integrin alpha 3 expression was closely associated with peritoneal dissemiantion, but there was no relationship between integrin alpha 3 expression and histologic type, nodal status, macroscopic type or wall invasion. Furthermore, 22 (84%) of 26 tumors which recurred in peritoneum overexpressed integrin alpha 3 expression in primary tumors. All seven peritoneal foci obtained from peritoneal dissemination expressed integrin alpha 3 expression despite no integrin alpha 3 expression in two of these 7 primary tumors. Reduced E-cadherin expression in primary tumors was intimately associated with large tumor size (>6 cm), nodal involvement, peritoneal dissemination and positive serosal invasion. Peritoneal dissemination was most frequently found in the tumors with positive integrin alpha 3 expression and reduced E-cadherin expression. Patients with these type of tumor [E-cadherin expression (-), and integrin alpha 3 subunit (+)] showed the poorest prognosis as compared with the other groups of patients. These results indicate that upregulation of integrin alpha 3 expression and down regulation of E-cadherin might have an important role in the formation of peritoneal dissemination. These tumors have characteristics of easy detachment from the serosal surface via downregulation of E-cadherin and strong adhesion capacity to the peritoneum via up-regulation of integrin alpha 3 expression. The immunohisto-chemical combination analysis of E-cadherin and integrin alpha 3 expression on the primary gastric cancer may be a good screening method to predict peritoneal recurrence.

E-cadherin and c-met expression as a prognostic factor in gastric cancer.

E-cadherin has an important role in the cell-cell adhesion and is known as an invasion suppressor gene. The c-met, which is a receptor of hepatocyte growth factor receptor, is involved in the proliferative and motile activity in cancer cells. The invasive and metastatic capacities of gastric cancer were studied from the immunohistochemically examined expression of MET and E-cadherin. Among 127 primary gastric cancers, 47 (34%) tumors were found to have preserved E-cadherin expression and the other 84 tumors showed reduced E-cadherin expression. MET expression was found in 55 (43%) tumors. A strong correlation was found between reduced E-cadherin expression and a larger tumor, positive serosal invasion, lymph node metastases or poor prognosis. Tumors with MET expression have the tendencies to invade deeply, to metastasize in more remote lymph nodes or peritoneum and to run a poor prognosis. MET over-expression and reduced E-cadherin expression were strongly associated with lymph node metastasis, peritoneal dissemination and poor prognosis. This group of patients with simultaneously abnormal expressions of these genes had a sixfold relative risk of death, as compared with patients with tumors showing MET negative or preserved E-cadherin expression. These results indicate that immunohistochemical combined analyses of MET and E-cadherin expression may be a powerful tool for the evaluation of invasive capacity and the prognosis of gastric cancer patients.

Correlation between expression of urokinase-type plasminogen activator receptor and metastasis in gastric carcinoma.

To clarify the interrelationship between urokinase-type plasminogen activator receptor (uPAR) and the progression of gastric cancer, uPAR expression in gastric cancer was studied by the reverse transcription (RT)-PCR and immunohistochemistry. uPAR mRNA was expressed in 44 of 46 primary gastric cancers and uPAR immunoreactivity was found in 21 (14%) of 155 tumors. uPAR immunoreactivity was also observed in the fibroblast-like cells and the inflammatory cells including macrophages. The intensity of uPAR immunoreactivity of these cells was weaker than that of cancer cells. uPAR expression detected by RT-PCR may be from cancer cells and/or non-cancerous stromal cells. uPAR immunoreactivity in cancer cells was closely associated with histologic type, nodal status, and macroscopic type. The uPAR positive tumors were closely associated with the macroscopically infiltrating type, undifferentiated type and stage IV disease. Poorly differentiated carcinomas with rich intestitial fibrosis (scirrhous carcinoma) expressed uPAR with a significantly higher incidence than the other histologic types of carcinoma. Growth of scirrhous carcinoma may be a result of a concerted action of the players in the plasminogen activator system, consisting of cancer cells and stromal elements. Furthermore, there was an intimate relationship between the grade of lymph node metastasis and uPAR tissue status. Patients with a uPAR positive tumor had a significantly poorer prognosis than those with uPAR negative tumor. These results indicate that the immunohistochemical diagnosis of uPAR tissue status on the primary tumor of gastric cancer may be a good predictor for the prognosis of patients with gastric cancer.

Association of progression and reduced expression of VLA-2 in gastric cancer.

We investigated the expression of VLA-2 in gastric cancers by immunohistochemistry using anti-integrin alpha 2 and beta 1 antibodies and the data were compared with the pathological findings of each gastric cancer. The specimens were stained with an immunohistological technique for integrin alpha 2 and beta 1 subunits. Tumors, simultaneously expressing both integrin alpha 2 and beta 1 subunits were defined as positive for VLA-2. Tumors expressing either subunits of integrin alpha 2 or beta 1 or those showing reduced expression of both subunits were defined as VLA-2 negative tumors. In the 77 primary tumors, 55 (71%) were VLA-2 positive. 38 (90%) of 42 tumors showing differentiated type including tubular adenocarcinoma and papillary adenocarcinoma expressed VLA-2, whereas 19 (55%) out of 35 undifferentiated type of cancers including poorly differentiated adenocarcinoma, mucinous carcinoma and signet ring cell carcinoma stained for VLA-2. In the undifferentiated type of cancers, VLA-2 negative tumors had a significantly higher incidence of vessel invasion than VLA-2 positive ones (p<0.05). VLA-2 negative tumors showed a tendency to peritoneal dissemination, lymph node metastases, lymphatic invasion or invasion beyond the subserosal layer. In the specimens of peritoneal dissemination, VLA-2 expression rate was found in 56% (9/16), with a higher expression rate than that of primary lesions. These data indicate that reduced expression of VLA-2 may strongly associate with vessel invasion especially in the undifferentiated type of adenocarcinoma of the stomach.

[Chemohyperthermic peritoneal perfusion and high-dose chemotherapy followed by peripheral blood stem cell transplantation in advanced colon cancer--a case report].

A 49-year-old woman who suffered from caecal cancer in 1988 underwent chemohyperthermic peritoneal perfusion for peritoneal and ovarian metastases in 1990, and high dose chemotherapy (HDC) with peripheral blood stem cell transplantation (PBSCT) for lung metastases in 1995. Heated saline containing anticancer drugs such as cisplatin, mitomycin C, etoposide (ETP), and pirarubicin, was intraperitoneally perfused at 43 degrees C for 60 minutes. The CD34 positive cells were mobilized by intravenous 500 micrograms G-CSF administration on five consecutive days. These cells were transplanted three days after the last day in the course of HDC, which included intravenous administration of 475 mg carboplatin, 2,020 mg cyclophosphamide, and 540 mg etoposide. The patient has survived with no sign of the disease.

Prognostic relevance of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitors PAI-1 and PAI-2 in gastric cancer.

Expression of urokinase-type plasminogen activator (uPA), plasminogen activator inhibitor-1 (PAI-1) and plasminogen activator inhibitor-2 (PAI-2) was evaluated in 125 surgically resected gastric cancers by immunohistochemical analysis. Tissue was stained immunohistochemically with a monoclonal antibody against human uPA and monoclonal antibodies against human PAI-1 and PAI-2. In addition, DNA ploidy patterns were determined by cytofluorometer after staining with propidium iodide. We found that 82 (66%) of the 125 gastric cancers expressed uPA as diffuse cytoplasmic staining, as intensely outlined luminal borders. PAI-1 expression was observed in 62 (50%) of 125 gastric cancer as a fine, diffuse and granular pattern in the cytoplasm. PAI-2 expression was observed in 65 (52%) of the 125 gastric cancers as a diffuse cytoplasmic staining. uPA-positive tumours showed a higher incidence of infiltration, lymph node metastasis and peritoneal dissemination that uPA-negative ones. Patients with uPA-positive tumours proved to have a significantly poorer prognosis than those with negative ones. PAI-1-negative tumours showed a higher incidence of liver metastasis and carried a poorer prognosis than PAI-1-positive ones. There was no significant correlation between uPA or PAI-1 expression and DNA ploidy patterns. Conversely, there was no significant relationship between PAI-2 expression and clinicopathological parameters and prognosis. According to the expression of uPA and PAI-1 status, groups of 19 uPA(-)/PAI-1(-), 44 uPA(+)/PAI-1(-), 23 uPA(-)/PAI-1(+) and 39 uPA(+)/PAI-1(+) were subdivided. Tumours with uPA(+)/PAI-1(-) had a significantly higher incidence of liver metastasis, lymph node metastasis and serosal invasion than the other groups of tumours. Patients with uPA(+)/PAI-1(-) tumours had a significantly poorer prognosis than those with uPA(-)/PAI-1(+) tumours. These results indicate that uPA expression is a useful biological prognostic indicator, and that uPA expression is a useful biological prognostic indicator, and that uPA and PAI-1 may play an important part in the tumour progression and metastasis in gastric cancer.

Mechanisms of the formation of the peritoneal dissemination in gastric cancer.

To clarify the mechanisms of the formation of peritoneal dissemination, a new animal model by the i.p. inoculation of highly metastatic gastric cancer cell line MKN-45-P was developed. Peritoneal dissemination with bloody ascites was found in 100% of nude mice, injected 1x10(7) MKN-45-P cells in suspension into the peritoneal cavity. By a highly sensitive method for specific detection of metastasized human tumor cells in nude mice using polymerase chain reaction, a human beta-globin-related sequence in the DNA from various parts of the peritoneum was specifically amplified and detected by gel electrophoresis and by a specific oligonucleotide probe. Greater omentum showed a strong signal of the amplified fragments of human beta-globin gene from the 1st day and the signals gradually increased. The signals in the gonadal fat, mesentery and ovarium could be weakly detected on the Ist day, transiently decreased on the 3rd day, and then increased from the 7th day. In the diaphragm, and abdominal wall, signals could be detected from the 7th day. In contrast, small intestine and colon did not show any human beta-globin signals. In greater omentum and gonadal fat, cancer cells were selectively detected in the milky spots stained by activated carbon on the 3rd day. In the diaphragm, cancer cells adhered to the small pores termed stomata, and invaded into the subdiaphragmatic lymphatic lacunae connected with stomata. From the 3rd day, mesothelial cells of the abdominal cavity became round and separated, resulting in the exposure of the underlying connective tissue. MKN-45-P cells were found to adhere to the naked areas of the submesothelial connective tissue. From these results, we conclude that the major metastatic route of the peritoneum may be firstly through milky spots, secondly through the diaphragmatic stomata, and thirdly by the adhesion to the naked connective tissue exposed after shrinkage of the mesothelial cells. The third process may be related to the interaction between some adhesion molecules and their ligands.

Roles of VLA-2 and VLA-3 on the formation of peritoneal dissemination in gastric cancer.

To clarify the mechanisms of the metastasis on the peritoneal surface from gastric cancer, a novel ex vivo co-culture system using human greater omentum and a highly metastatic cell line, MKN-45-P was developed. MKN-45-P was established from a gastric cancer cell line of MKN-45 by the progressive growing of the intraperitoneal passages. The differences of the expression of metastasis related genes between MKN-45 and MKN-45-P were examined by RT-PCR. Cancer cells adhered only to the naked area of the submesothelial basement membrane, which was exposed by the shrinkage and exfoliation of mesothelial cells of the omentum. The expressions of integrin alpha 2 and alpha 3 subunits in MKN-45-P were extremely elevated compared to those in MKN-45. Integrin beta 1 subunit expression did not change during the intraperitoneal passages. Anti-beta 1 integrin subunit antibody significantly inhibited the adherent number of MKN-45-P on the omentum. These results indicate that VLA-2 and VLA-3 may have an important role in the formation of the peritoneal dissemination from gastric cancer.