Synchronous adenocarcinoma and mantle cell lymphoma of the stomach

Synchronous occurrence of mantle cell lymphoma (MCL) and gastric cancer in the same patient has not yet been reported in the English literature. MCL comprises 2.5-7% of non-Hodgkin's lymphomas and is characterized by a poor prognosis with a median survival probability of 3-4 years in most series. A 62-year-old man was referred to our hospital for evaluation of an abnormal gastric lesion. The endoscopic finding was compatible with type IIc early gastric cancer (EGC) in the middle third of the stomach, and a biopsy of the lesion proved to be carcinoma. Radical total gastrectomy with splenectomy and Roux-en-Y esophagojejunostomy were performed. The resected specimen revealed two grossly separated lesions. Postoperative histological examination reported both adenocarcinoma and MCL. Immunohistochemical staining showed positivity for CD5, CD20, and cyclin D1 in the infiltrated lymphoid cells. MCL is an aggressive non-Hodgkin's lymphoma, and the current treatment approach is still unsatisfactory. Further advancements in the understanding of the synchronous occurrence of both diseases, and more efforts on investigations of treatment are needed.     

Primary Hodgkin lymphoma of the stomach--a case report

A case of a 69-year-old male with a one-month history or recurrent attacks of GI bleeding, secondary anemic syndrome and epigastric pain is reported. Endoscopic examination revealed a tumorous lesion suspicious of malignancy. Neither lymphadenopathy nor any other tumorous lesion was identified by extensive clinical examination. In the biopsy specimens there was ulcerated gastric mucosa with an infiltration by lymphoid cells, predominantly of mature T-cell type. Atypical large cells with large nuclei with prominent nucleoli were dispersed among the mature lymphocytes. These atypical cells were both mono- and binucleated (Hodgkin and RS cells). Both cell types revealed immunohistochemically membranous and dot-like perinuclear positivity of CD30 and CD15 antigens. Based on morphologic features and immunohistochemical findings, a diagnosis of primary gastric Hodgkin lymphoma was established. Diagnostic approach, as well as differential diagnosis of primary Hodgkin lymphoma in this extremely rare location, are discussed.     

Granzyme B-positive primary gastric T-cell lymphoma: gastric T-cell lymphoma with the possibility of extrathymic T cell origin

A case of primary gastric T-cell lymphoma, which was positive for granzyme B, is reported. The patient was a 47-year-old Japanese female who complained of a dull upper abdominal pain. Radiographic and endoscopic examinations revealed an ulcerative infiltrative lesion in her stomach. Following the confirmation of a high-grade malignant lymphoma, a distal gastrectomy with regional lymph nodal dissection was performed. The histology of the gastric lesion revealed a malignant lymphoma of the diffuse pleomorphic type without lymph nodal involvement. Immunohistochemistry revealed that the tumor cells were positive for LCA, CD3, TIA-1 and granzyme B, but were negative for CD4, CD8, CD56, CD30, L-26, EMA, TCR alpha/beta and TCR gamma/delta. Because the tumor cells showed T cell nature with cytotoxic activity proved by TIA-1 and granzyme B, and without evidence of further maturation of T cell, a malignant lymphoma originating from extrathymic-derived T cells was suggested.     

A Case of Pulmonary Adenocarcinoma with Sarcomatous Elements Initially Manifested as a Submucosal Tumor of the Stomach

A case of pulmonary adenocarcinoma, which was initially manifested as a gastric submucosal tumor, is presented. Endoscopy showed a submucosal tumor in the fundic region in a 79-year-old Japanese woman. Initial biopsy specimens of the stomach revealed atypical spindle cell proliferation, suggesting primary leiomyosarcoma of the stomach. However, biopsy specimens obtained one year later were diagnosed as malignant lymphoma or malignant histiocytosis of the stomach. Autopsy revealed a large necrotic lesion in the right S₈ region with metastases in multiple organs. Microscopy demonstrated well to moderately differentiated adenocarcinoma containing spindle or pleomorphic sarcomatous elements. Metastatic nodules including the gastric tumors all showed sarcomatous elements with no epithelial component. Immunohistochemistry showed positive reactions for keratin, epithelial membrane antigen, and carcinoembryonic antigen in areas of carcinoma, whereas most of the sarcomatous elements revealed no positivity for any of the antibodies used, except for focal keratin and EMA positivity in the primary site. This is a rare case of pulmonary adenocarcinoma with sarcomatous elements discovered as a gastric tumor at initial diagnosis, resulting from metastasis of the sarcomatous element in the submucosa.     

Collision of EBV‐associated gastric carcinoma and primary gastric extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue in the remnant stomach

Reported herein is a case of EBV‐associated gastric carcinoma with primary gastric extranodal marginal zone lymphoma of mucosa‐associated lymphoid tissue (MALT lymphoma). A 69‐year‐old Japanese man was found to have an ulcer lesion in his stomach on endoscopy, and a biopsy indicated malignancy. He underwent gastrectomy. Microscopically the tumor had features typical of lymphoepithelioma‐like carcinoma. The neoplastic epithelial cells proliferated in a trabecular fashion. On in situ hybridization for EBV‐encoded RNA, positive signals were observed in most neoplastic epithelial cells. Numerous lymphocytes surrounded the neoplastic epithelial cells. In the stroma, numerous lymphocytes with mild atypia were positive for CD20 and CD79a. In addition, monoclonal proliferation of B cells was confirmed on polymerase chain reaction for IgH. These findings supported MALT lymphoma. The coexistence of EBV‐associated gastric carcinoma and MALT lymphoma is extremely rare.     

Primary gastric Ki-1 positive anaplastic large cell lymphoma: A report of two cases

Two cases with primary gastric Ki-1 positive anaplastic large cell lymphoma are presented. Morphologic features of both cases involved pleomorphism of the neoplastic cells, fibrosis and lymphatic infiltration. The neoplastic cells in both cases were positive for BerH₂ (CD30), LCA(CD45), lysozyme and alpha-1-antitrypsin (α₁-AT). In additional case, the neoplastic cells were additionally positive for MAC387 and (α₁,-antichymotrypsin (α,-ACT). The neoplastic cells in these cases were negative for L26(CD20), UCHL-1 (CD45RO), DAKO CD3 and epithelial membrane antigen (EMA). According to the results of the phenotypic studies, the authors consider that the neoplastic cells have some of the features of histiocytes.
Both patients at 2 and 8 years after surgery without chemotherapy are disease free. This lymphoma is well known to be frequently misdiagnosed as undifferentiated carcinoma. Although rare in occurrence, recognition of this primary lymphoma in the stomach has a significant clinical implication, as the authors consider that its prognosis might be better than undifferentiated carcinoma of the stomach.     

Adenocarcinoma at the esophageal gastric junction arising in an 11-year-old girl

Gastric adenocarcinoma is one of the most common gastrointestinal (GI) malignancies, especially among Japanese adults, but represents only 0.05% of all malignant pediatric GI tumors. We report a case of gastric adenocarcinoma arising at the esophageal gastric junction of an 11-year-old girl. The tumor was polypoid, measuring 3.0 x 3.0 x 1.2 cm and was light gray and partially red in color with a stalk. Light microscopic examination of the lesion demonstrated adenocarcinoma of variable degrees of both architectural and nuclear atypia with invasion into the submucosa. Immunohistochemical findings of cytokeratin subtypes revealed positive immunoreactivity for cytokeratin subtypes 8, 19 and 20 and negative for 5/6/18, 7, 13 and 14, which is consistent with those of gastric adenocarcinoma. The patient was alive and well 12 months postoperatively.     

Dissecting expression profiles of gastric precancerous lesions and early gastric cancer to explore crucial molecules in intestinal-type gastric cancer tumorigenesis

Intestinal-type gastric cancer (IGC) has a clear and multistep histological evolution. No studies have comprehensively explored gastric tumorigenesis from inflammation through low-grade intraepithelial neoplasia (LGIN) and high-grade intraepithelial neoplasia (HGIN) to early gastric cancer (EGC). We sought to investigate the characteristics participating in IGC tumorigenesis and identify related prognostic information within the process. RNA expression profiles of 94 gastroscopic biopsies from 47 patients, including gastric precancerous lesions (GPL: LGIN and HGIN), EGC, and paired controls, were detected by Agilent Microarray. During IGC tumorigenesis from LGIN through HGIN to EGC, the number of activity-changed tumor hallmarks increased. LGIN and HGIN had similar expression profiles when compared to EGC. We observed an increase in the stemness of gastric epithelial cells in LGIN, HGIN, and EGC, and we found 27 consistent genes that might contribute to dedifferentiation, including five driver genes. Remarkably, we perceived that the immune microenvironment was more active in EGC than in GPL, especially in the infiltration of lymphocytes and macrophages. We identified a five-gene signature from the gastric tumorigenesis process that could independently predict the overall survival and disease-free survival of GC patients (log-rank test: p < 0.0001), and the robustness was verified in an independent cohort (n > 300) and by comparing with two established prognostic signatures in GC. In conclusion, during IGC tumorigenesis, cancer-like changes occur in LGIN and accumulate in HGIN and EGC. The immune microenvironment is more active in EGC than in LGIN and HGIN. The identified signature from the tumorigenesis process has robust prognostic significance for GC patients. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Multiple lymphomatous polyposis of the gastrointestinal tract is a heterogenous group that includes mantle cell lymphoma and follicular lymphoma: analysis of somatic mutation of immunoglobulin heavy chain gene variable region.

Multiple lymphomatous polyposis (MLP) is characterized by multiple polyps involving long segments of the gastrointestinal (GI) tract. MLP is thought to represent mantle cell lymphoma (MCL) of the GI tract; however, some cases of follicular lymphoma (FL) of the GI tract are found with a multiple polypoid appearance. In the present study, to clarify the cellular origin of MLP, clonal immunoglobulin heavy chain (IgH) gene rearrangement of four cases with MLP was amplified by polymerase chain reaction (PCR) and analyzed for the presence of somatic mutation. The IgH variable (VH) region sequences of three cases (CD5+ CD10- cyclin D1+) showed a little somatic mutation compared with the closest published germline. The other case (CD10+ CD5- cyclin D1-) was highly mutated and showed intraclonal heterogeneity (ongoing somatic hypermutation). These data indicate that three of the cases with MLP are derived from pregerminal center B cells (mantle zone B cells) and one case with MLP from germinal center B cells. Our study suggests that MLP is a heterogenous group that includes MCL and FL.     

A case of primary gastric CD30-positive anaplastic large-cell lymphoma

Gastric CD30-positive anaplastic large-cell lymphoma is a very rare disease. It is sometimes difficult to distinguish it from undifferentiated carcinoma, sarcoma and so on. We report here on a case of primary gastric anaplastic large-cell lymphoma. A 50-yr-old woman complained of epigastric pain and severe chest pain for 1 week. The gastroendoscopic examination revealed geographic mucosal irregularities with shallow ulceration at the antrum. She underwent a total gastrectomy. The gross finding of the resected stomach was an 8 x 4.5 cm sized ulceroinfiltrative lesion at the pyloric antrum along the lesser curvature. The microscopic examination revealed diffuse and solid proliferations of large atypical cells with pleomorphic nuclei. Immunohistochemically, the tumor cells were positive for CD30, vimentin and CD3, and this was a finding compatible with anaplastic large-cell lymphoma. To the best of our knowledge, this is the first such reported case in Korea.     

基层医院56例早期胃癌胃镜下表现的分析

目的探讨早期胃癌(EGC)普通胃镜下的表现,为提高基层医院EGC的检出率提供参考。方法回顾性分析我院确诊的早期胃癌56例患者的内镜下表现,包括发生部位、大小、分型及各型表现以及亚甲蓝着色特征。结果 56例患者中,病灶位于胃窦部22例(39.3%),胃体部18例(32.1%),胃角部10例(17.9%),贲门部6例(10.7%)。单个病灶直径为0.5~2.6 cm,平均(1.28±1.36)cm。Ⅰ型(隆起型)12例(21.4%),Ⅱ型(平坦型)36例(64.3%),其中Ⅱa型(浅表隆起型)10例(17.9%),Ⅱb型(浅表平坦型)2例(3.6%),Ⅱc型(浅表凹陷型)24例(42.9%),Ⅲ型(溃疡型)2例(3.6%)。56例患者经亚甲蓝染色后,病变黏膜呈黑色或深蓝色48例(85.7%),浅蓝色6例(10.7%),不着色2例(3.6%)。结论 EGC好发于胃窦部,以Ⅱc型为主,多数病变亚甲蓝染色呈深蓝色。     

Mantle cell lymphoma with a unique pattern of CD5 expression: a case report with review of the literatures

Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin’s lymphoma characterized by chromosomal translocation t(11;14)(q13;q32), positive CD5, and nuclear cyclin D1 overexpression with unfavorable prognosis. We report herein a case of MCL in a 73-year-old male diagnosed with diffuse large B-cell lymphoma (ileal tumor) at another hospital, who subsequently relapsed with CD5-negative MCL. At the 1st relapse, he developed neck lymph node swelling, of which biopsy showed proliferation of atypical large pleomorphic cells with CD5-negativity by both immunohistochemistry and flow cytometry. At the 2nd relapse, he again developed an ileal tumor, of which biopsy showed positivity for CD5, CD20, and cyclin D1. In MCL, CD5-negative expression has sometimes been reported as having pleomorphic and blastoid variants. The present case was also histologically the pleomorphic type, but the CD5 expression changed from negative at the onset and the 1st relapse to positive at the 2nd relapse. This is a rare and interesting case because of the different expression of CD5 at all stage. This phenomenon made the diagnosis of MCL difficult.     

One patient with double lymphomas: simultaneous gastric MALT lymphoma and ileal diffuse large B-cell lymphoma

Multiple different lymphomas in a single person are very rare. The author herein reports the case of a 69- year-old Japanese woman with double gastrointestinal lymphoma. The patient presented with epigastralgia. Endoscopic examination revealed erosions and elevation of the gastric body and a large ulcerated tumor of the terminal ileum. Biopsies were obtained from these lesions. The gastric lesion was MALT lymphoma with monocytoid B-cell proliferation and lymphoepithelial lesions. Light chain restriction was present. Helicobacter pylori were present on Giemsa stain. The gastric lesions did not regress despite of therapy, which were confirmed by follow-up biopsy. The ileal lesion was obvious diffuse large B-cell lymphoma. The lesion regressed by chemotherapy. The patient is now alive 3 years after the first presentation.     

Immunoreactivity of neoplastic and non-neoplastic monocytoid B lymphocytes for DBA.44 and other antibodies.

AIMS--To evaluate the immunoreactivities of neoplastic and non-neoplastic monocytoid B cells (MBC) and compare them with hairy cell leukemia (HCL) and mantle cell lymphoma (MCL). METHODS--An immunohistochemical study of paraffin wax embedded sections was done on surgically resected specimens of spleens with MBC clusters from patients with gastric cancer (14 cases), tonsils (five cases), and lymph node (two cases) showing lymphoid follicular hyperplasia (LFH), submandibular lymph nodes containing MBC in Sjögren's syndrome (one case). Extranodal organs affected by MCL (three cases) and monocytoid B cell lymphoma (MBCL) (seven cases), and spleens from HCL (four cases) were also studied. These specimens were fixed in 10% formalin and routinely processed for paraffin wax embedding. Fresh spleen specimens from patients with liver cirrhosis (one case) and gastric cancer (seven cases) were snap frozen. RESULTS--Mantle zone lymphocytes were DBA.44, CD74 positive and showed a weaker reaction for CDw75 than marginal zone lymphocytes and MBC, which were almost DBA negative. In neoplastic diseases tumour cells in MCL were DBA.44, CD74, and CDw75 positive. MBCL showed a positive reaction for CD74 and CDw75, but positivity for DBA.44 was observed in only one of seven cases. The HCL specimens, all positive for DBA.44, showed a weaker reaction for CD74 and a stronger reaction for CDw75 than either MCL and MBCL specimens. CONCLUSION--These results show that mantle zone lymphocytes and MCL more closely matched HCL for reactivity to DBA.44 than MBC and MBCL. Reactivities for DBA.44 and CDw75 were greater in MBCL compared with its non-neoplastic counterpart, MBC.     

Detection of the Epstein-Barr virus in primary gastric lymphoma by in situ hybridization

The Epstein-Barr virus (EBV) has been shown to be associated with numerous human malignancies including Burktt's lymphoma and nasopharyngeal lymphoepithelioma. In addition, some typical gastric adenocarcinomas were also recently reported to demonstrate EBV relevance. The present study was designed to detect EBV in primary gastric lymphoma, using the in situ hybridization (ISH) method, in which oligo-nucleotide probes for the EBERl RNA and the EBV DNA W region have been used. Of the 49 cases of primary gastric lymphoma studied, which all showed B cell immunopheno-type, EBER1 sequences could only be found in four cases, including two low-grade cases and two high-grade cases of histological subtypes while the number of positive cells was less than 50% of the tumor cells. In one case of low-grade mucosa associated lymphoid tissue (MALT) lymphoma, the EBER1 -positive neoplastic cells were found in the regional lymph node, but the primary site of the stomach showed no positive signals. The EBV presence was further confirmed by the EBV DNA ISH. Using the ISH method, rare or occasional positive lymphoid cells (probably non-tumorous bystander cells) could be detected in 10 other cases including all histological subtypes. The present study shows that only a small proportion of primary gastric lymphoma is associated with EBV, and such positive cases could be found in both high- and low-grade histological subtypes. It is also suggested that the EBV presence in the neoplastic cells of some cases of primary gastric lymphoma is most likely a secondary phenomenon.     

Frequent expression of CD30 antigen in the primary gastric non-B, non-Hodgkin lymphomas

Most primary gastric lymphomas are of B-cell origin. Fourteen cases of primary gastric non-B, non-Hodgkin lymphomas were studied to evaluate their clinicopathological and immunophenotypic findings. The cases were comprised of 11 men and three women, with a median age of 56.5 years. Most patients underwent surgery either with or without chemotherapy, exhibiting a 5 year survival rate of 57.5%. Morphologically, the neoplastic cells showed various histological features, such as anaplastic large cell lymphoma (ALCL) (n = 3), peripheral T-cell lymphoma, unspecified, large (n = 4), medium-sized (n = 2) and mixed cell (n = 5). Two cases displayed a non-B, non-T cell phenotype, whereas the remaining cases displayed a T-cell phenotype. Six cases were CD4+, while two were CD8+. The neoplastic cells were CD30+ in 10 cases. TIA-1 was positive in six cases. In one case, anaplastic large cell lymphoma kinase (ALK) was identified with immunostaining and chromosomal rearrangement of ALK was detected by fluorescence in situ hybridization (FISH). In conclusion, although the mechanism of CD30 expression is unknown, primary gastric non-B, non-Hodgkin lymphomas tend to express CD30. We consider that some of the cases in the present study may be derived from cytotoxic T cells, similar to systemic and cutaneous ALCL, the majority of which exhibit TIA-1.     

Simultaneous hepatocyte paraffin-1-positive α-fetoprotein-producing gastric adenocarcinoma and gastric mucosal-associated lymphoid tissue

An 85-year-old Japanese woman was admitted to our hospital because of abdominal fullness. Computed tomography revealed multiple nodules in the liver; the interpretation was metastatic carcinoma. Serum laboratory test revealed extremely elevated α-fetoprotein (AFP) (8820 ng/mL; normal, <10 ng/mL). Upper and lower gastrointestinal endoscopy was performed and identified a large type-2 advanced gastric carcinoma and mucosal irregularity of the antrum. Biopsies were performed. The gastric carcinoma was well-differentiated papillotubular adenocarcinoma. Immunohistochemically, it was positive for pancytokeratins, AFP, hepatocyte paraffin-1 (HepPar1), p53 protein, and Ki-67 antigen (labeling, 70%) but was negative for vimentin, CEA, CA19-9, and lymphoid cell markers. Therefore, the lesion was diagnosed as AFP-producing gastric carcinoma with HepPar1 positivity. The biopsies of the gastric mucosal irregularity revealed severe lymphoid infiltration. The lymphoid cells were centrocyteslike cells with plasma cell differentiation and, immunohistochemically, were composed of CD20-positive B cells. A small number of CD3-positive T cells were also seen. Lymphoepithelial lesions were recognized. Therefore, the lesion was diagnosed as mucosal-associated lymphoid tissue lymphoma. Helicobactor pylori were recognized on Giemsa stain. The present case showed that AFP-producing gastric adenocarcinoma and mucosal-associated lymphoid tissue lymphoma can coexist. They may be associated with H. pylori infection. It was also interesting that the AFP-producing gastric carcinoma expressed HepPar1.     

Lymphomatous polyposis of the gastrointestinal tract, including mantle cell lymphoma, follicular lymphoma and mucosa-associated lymphoid tissue lymphoma

AIMS: Lymphomatous polyposis (LP) is considered to represent mantle cell lymphoma (MCL) of the gastrointestinal (GI) tract. However, a few reports have suggested that some are follicular lymphoma (FL) or mucosa-associated lymphoid tissue (MALT) lymphomas. In this study, we analysed 35 patients and clarified the clinicopathological features of LP. METHODS AND RESULTS: Paraffin-embedded tissue samples were stained immunohistochemically and analysed by tissue-fluorescence in situ hybridization (T-FISH) for IGH/CCND1 (cyclin D1) and IGH/BCL2. The average age of the patients was 58.3 years. Over half of the cases showed gastric, duodenal, small intestinal, ileocaecal and sigmoid colonic lesions (15, 19, 15, 16 and 16 cases, respectively). Phenotypically, cases were classified into three types of MCL (cyclin D1+ CD5+ CD10-) (n=12), FL (cyclin D1- CD5- CD10+) (n=14) and MALT (cyclin D1- CD5- CD10-) (n=9). T-FISH identified 11 of the 11 examined cases with MCLs to have IGH/CCND1, while seven of 10 cases with FL had IGH/BCL2, and none of the MALT cases were positive for IGH/CCND1 or IGH/BCL2. At the study endpoint, five of 12 patients with MCL were dead, two of 14 with FL and one of nine with MALT were dead of other disease. Event-free survival analysis showed significantly poorest outcome in MCL, followed by FL, while MALT was associated with a favourable outcome (P=0.0040). CONCLUSIONS: Our study emphasizes the importance of differentiating MCL, FL and MALT of LP in evaluating prognosis and hence the most suitable therapeutic regimen.     

The mutational burdens and evolutionary ages of early gastric cancers are comparable to those of advanced gastric cancers

Early gastric cancers (EGCs) precede advanced gastric cancers (AGCs), with a favourable prognosis compared to AGC. To understand the progression mechanism of EGC to AGC, it is required to disclose EGC and AGC genomes in mutational and evolutionary perspectives. We performed whole‐exome sequencing and copy number profiling of nine microsatellite (MS)‐unstable (MSI‐H) (five EGCs and four AGCs) and eight MS‐stable (MSS) gastric cancers (four EGCs and four AGCs). In the cancers, we observed well‐known driver mutations (TP53, APC, PIK3CA, ARID1A, and KRAS) that were enriched in cancer‐related pathways, including chromatin remodelling and tyrosine kinase activity. The MSI‐H genomes harboured ten times more mutations, but were largely depleted of copy number alterations (CNAs) compared to the MSS cancers. Interestingly, EGC genomes showed a comparable level of mutations to AGC in terms of the number, sequence composition, and functional consequences (potential driver mutations and affected pathways) of mutations. Furthermore, the CNAs between EGC and AGC genomes were not significantly different in either MSI‐H and MSS. Evolutionary analyses using somatic mutations and MSI as molecular clocks further identified that EGC genomes were as old as AGC genomes in both MSS and MSI‐H cancers. Our results suggest that the genetic makeup for gastric cancer may already be achieved in EGC genomes and that the time required for transition to AGC may be relatively short. Also, the data suggest a possibility that the mutational profiles obtained from early biopsies may be useful in the clinical settings for the molecular diagnosis and therapeutics of gastric cancer patients. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

The 5D4 antibody (anti-cyclin D1/D2) related antigen: Cytoplasmic staining is correlated to the progression of gastric cancer

In order to clarify the relationship between cyclin D1 and 02 (CD1/CD2) overexpression and progression, 191 gastric cancer cases (81 early and 110 advanced cancers) were investigated using the 504 monoclonal antibody for both CD1/CD2 in immunohistochemistry. 5D4 immunoreactlvity was noted in 68 (35.6%) cases, staining being restricted to the nucleus In 27 (14.1%) cases, the cytoplasm in 34 (17.8%) cases, and its presence in both the nucleus and cytoplasm in seven (3.7%). Cases demonstrating cytoplasmic positiv-ity, including both positive cases, were significantly more frequent in advanced cancers (P = 0.010), those having lymph node metastasis ( P = 0.004) and cases showing cancer invasion of vessels (P = 0.00S), although no relatlon to histological malignant grading was apparent. In contrast, cases of nuclear positivity behaved no differently from 5D4-negative cases. Statistics showed a trend where survival in patients was worse in the cytoplasm-positive cases than the cytoplasm-negative group. However, multivariate analysis revealed no Independent statlstical significance in the cytoplasmic positivity of prognosis. Additional studies using DCS-6 antlbody for CD1 and 617 antibody for CD2, suggest that nuclear staining of 5D4 indicates the presence of CD1 but cytoplasmic staining is derived from an antigen that is related to CD2. In conclusion, the present results indicate that the accumulation of CD2 in the cytoplasm may play some role In the progression of gastric cancers but not prognosis; however, CD1 overexpression is not linked to either.