Expression of trefoil group antigen pS2 in human gastric cancer

Expression of trefoil group antigen pS2 was examined immunohistochemically in resected stomachs from 121 patients with gastric cancer. Gastric cancer was classified as either undifferentiated or differentiated by histology, and was also divided into gastric type or non-gastric type by mucin-histochemistry. Immunoreactive pS2 was present in 20% of early cancers and 30% of advanced cancers (NS), and in 25% of undifferentiated and 15% of differentiated early cancers (NS), whereas the antigen was present in 38% of undifferentiated and 15% of differentiated advanced cancers (p = 0.04). Positivity for pS2 was found more often in gastric type early cancer (p = 0.04) as well as advanced cancer (p = 0.0002), and was also more frequent in cancers showing scirrhous (p = 0.04) and infiltrative growth (p = 0.03). Cancer positive for pS2 was characterized by mucin-histochemistry and microscopy as gastric type with scirrhous growth and diffuse infiltration, and thus the expression of pS2 in gastric cancer appears to be related to the growth of cancer with these characteristics.     

Distribution of transforming growth factor-beta and its receptors in gastric carcinoma tissue

The distribution of the three mammalian isoforms of transforming growth factor (TGF)-beta (TGF-beta 1, -beta 2, and -beta 3) as well as their signaling receptors, TGF-beta type I and type II receptors (T beta R-I and T beta R-II, respectively), in gastric carcinoma tissue was examined by immunohistochemistry using specific antibodies. Tissue specimens were obtained from 25 cases of gastric carcinoma, which were classified into two groups according to Lauren's classification, i.e. 15 cases of diffuse carcinoma and 10 cases of intestinal carcinoma. In normal gastric mucosa apart from carcinoma nests, all of TGF-beta 1, -beta 2, -beta 3, T beta R-I and T beta R-II were clearly demonstrated in fundic glands. In sharp contrast, none of them was detectable in surface mucous cells. In carcinoma cells, strong staining for TGF-beta 1, -beta 2 and -beta 3 was obtained only in diffuse-type carcinoma. In particular, carcinoma cells scattered as single cells or small nests had a tendency to show strong staining for TGF-betas. The receptors tended to be distributed concomitantly with the ligands, and diffuse-type carcinoma showed stronger receptor staining than intestinal-type carcinoma. In cancer stroma, TGF-betas and receptors were detected in both diffuse and intestinal types, but the area with positive staining was wider and more dispersed in diffuse-type carcinoma than in intestinal carcinoma. These results suggest that TGF-beta may contribute in part to the variety of histogenesis and mode of progression of gastric carcinoma.     

Genomic structure and chromosomal localization of the human interleukin 15 gene (IL-15)

The morphologic and functional characteristics of cultured hair follicle dermal papilla (DP) cells, dermal sheath (DS) cells and interstitial dermal fibroblasts (DF cells) derived from human scalp tissue are compared. DP and DS cells, but not DF cells, showed aggregative behavior at a preconfluent density. All three types of cells stained positive for type I collagen, type IV collagen, laminin and heparan sulfate proteoglycan. Only DP and DS cells expressed smooth muscle alpha-actin. DP and DS cells also synthesized more glycosaminoglycans (GAG) than DF cells, while there was no significant difference between DP and DS cells in GAG synthesis. Ultrastructurally, 7 out of 10 strains of DP and 2 out of 10 strains of DS cells were found to form intranuclear rodlets, while none of the 10 strains of DF cells examined formed intranuclear rodlets. The conditioned medium of the three types of cells was collected and tested for the presence of interleukin (IL)-1 beta, tumor necrosis factor (TGF)-beta 2, IL-6, platelet-derived growth factor-AB, epidermal growth factor, b-FGF, GM-CSF, insulin-like growth factor (IGF)-1 and HGF (hepatocyte growth factor) by ELISA or RIA. Among the tested cytokines and growth factors, TGF-beta 2, IL-6 and IGF-I were detectable in at least some conditioned media. The others were undetectable. There was no significant difference in the production of IL-6 and IGF-I among the three types of cells. In contrast, DP cells produced the highest levels of TGF-beta 2, DS cells produced intermediate levels of TGF-beta 2, and DF cells produced the lowest levels of TGF-beta 2. DP and DS cells are morphologically and functionally different from the nonfollicular, interstitial DF cells. Moreover, the presence of some minor biologic differences between DP and DS cells suggests that they represent follicular mesenchymal cells in different functional or differentiation states.     

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: ethosuximide, trimethadione, and dimethadione

The state of the basement membrane (BM) was investigated in the normal epithelium, dysplasia/carcinoma in situ (CIS) and invasive carcinoma of the uterine cervix as well as metastatic lymph nodes by performing immunohistological staining for the presence of laminin (LN) and type IV collagen (CIV) and periodic acid-methenamine silver (PAM) staining of the BM. Moreover, to clarify the relationship between the epithelial cells and the BM, simultaneous staining for proliferating cell nuclear antigen (PCNA) was performed on the repaired tissue after punch biopsy. In the normal tissues, positive linear staining was observed beneath the epithelium with both PAM staining and LN.C IV staining. Some of the cases of dysplasia/CIS were continuously positive with PAM staining. However, there were sites which showed weakening and disruption of the continuity of positive staining for LN and C IV. As a function of the histological type of invasive carcinoma, the intensity of staining for LN and C IV decreased in the order of keratinizing (K), large cell non-keratinizing (LNK) and small cell non-keratinizing (SNK) histological types. However, no correlation was found between the stage of the carcinoma and the intensity of staining. In addition, the staining of the metastatic lymph nodes was similar to that of the primary lesion, and cancer foci that were in direct contact with lymphocytes were also stained for LN and C IV. During the process of reformation of the BM, LN and C IV were already present at the time when the epithelial interstitium was still negative for PAM staining. Moreover, at the time when the epithelial basal cells were PCNA-positive, LN and C IV could not be detected, and, conversely, when PCNA was negative, LN and C IV were detected. The BM is a structure which is formed when the interstitium is in a static state, and it was surmised that the production of LN and C IV is carried out by epithelial cells, including cancerous cells. Furthermore, it was surmised that the BM is not a structure which can prevent cancer invasion and the discontinuity or intermittency of staining for LN and C IV in cancers is a result of changes in the capacity to produce the BM components due to canceration of the cells.     

Modulation of collagen gene expression by cytokines: stimulatory effect of transforming growth factor-beta1, with divergent effects of epidermal growth factor and tumor necrosis factor-alpha on collagen type I and collagen type IV

Transforming growth factor-beta1 (TGF-beta1) is well recognized as a potent mediator of both fibrillar (collagen type I) and basement membrane (collagen type IV) production. However, tissue injury is characterized by the concomitant expression of many cytokines and/or growth factors in addition to TGF-beta1, and the ultimate extent of extracellular-matrix (ECM) deposition may reflect the interacting effects of TGF-beta1 and these other cytokines and/or growth factors. We, therefore, sought to determine whether other cytokines and/or growth factors, known to be produced after tissue injury, are capable either alone or in combination with TGF-beta1 of modulating collagen gene expression. Collagen type I and collagen type IV gene expression was assessed in NIH-3T3 cells, a murine fibroblast-like cell line that responds to TGF-beta1, with increases in both collagen type I and collagen type IV production. TGF-beta1 coordinately induced production of collagen type IV messenger ribonucleic acid (mRNA) to a level 3.8-fold above its baseline value (p < 0.001) and collagen type I mRNA to a level 2.6-fold above its baseline value (p < 0.001). Of the other cytokines and/or growth factors tested, only epidermal growth factor (EGF) had significant effects on collagen mRNA expression. We report the novel observation that EGF significantly induced collagen type IV mRNA (3.0-fold; p < 0.001) but did not alter collagen type I mRNA expression. Platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and insulin-like growth factor-1 (IGF-1) did not alter the expression of mRNA for collagen type IV or collagen type I. Addition of TGF-beta1 to cytokine- and/or growth factor-treated cells increased both collagen type IV and collagen type I mRNA levels. However, collagen type IV mRNA levels were similar in cultures given TGF-beta1 alone and cultures given TGF-beta1 with other cytokines and/or growth factors; there were no additive, synergistic, or antagonistic effects after coadministration of TGF-beta1 and other cytokines and/or growth factors. With regard to collagen type I mRNA expression, all cytokines and/or growth factors tested, with the exception of TNF-alpha, had no effect on collagen type I mRNA levels in TGF-beta1-treated cultures. Importantly, TNF-alpha antagonized the stimulatory effect of TGF-beta1 on collagen type I mRNA levels. These observations support a dominant role for TGF-beta1 in stimulating coordinate expression of collagen type I and collagen type IV mRNAs by NIH-3T3 cells; EGF and TNF-alpha are capable of inducing divergent expression of the genes for these two types of collagen.     

Expression of CD44 standard and CD44 variant 6 in human lung cancer

We immunohistochemically examined the expression of CD44 standard (CD44 st) and CD44 variant 6 (CD44 v6) in 112 cases of primary lung cancer, and their relationship to the clinical milieu, including the clinical stage. In 46 cases of squamous cell carcinoma, expression of CD44 st was observed in 45.7% of the cases, and expression of CD44 v6 was observed in 60.9%. In 43 cases of adenocarcinoma, positive staining of CD44 st and CD44 v6 was seen in 2.3% and 4.7% of the cases, respectively. None of 21 small cell carcinomas was positive for CD44 st or CD44 v6. In squamous cell carcinomas, the expression of CD44 st and CD44 v6 was observed at a rate significantly higher than in other histologic type. Most specimens positive for CD44 st stained positively for CD44 v6. Therefore, it seems likely that the CD44 expression observed in squamous cell carcinoma of the lung was a variant CD44 containing the domain encoded by variant exon 6. The expression of CD44 v6 was not related to the clinical stage. Significant association between CD44 v6 and differentiation of squamous cell carcinoma was seen; 2/7 (28.6%) for poorly differentiated, 19/31 (61.3%) for moderately differentiated, and 7/8 (87.5%) for well differentiated squamous cell carcinomas (p = 0.02 by trend test). It was previously reported that CD44 st and CD44 v6 were expressed in both normal bronchial epithelium and squamous cell metaplasia. These results suggest that the expression of CD44 v6 in squamous cell carcinoma of the lung may reflect the immunohistochemical characteristics of the tissue from which such carcinoma emerge.     

Angiotensin converting enzyme inhibition reduces the expression of transforming growth factor-beta1 and type IV collagen in diabetic vasculopathy

OBJECTIVE: The purpose of this study was to assess the role of transforming growth factor (TGF)-beta1 in the development of diabetes-associated mesenteric vascular hypertrophy and in the antitrophic effect of angiotensin converting enzyme inhibitors. DESIGN AND METHODS: Streptozotocin-induced diabetic and control Sprague-Dawley rats were randomly allocated to treatment with the angiotensin converting enzyme inhibitor ramipril or to no treatment and were killed 1 or 3 weeks after the streptozotocin injection. Blood was collected and mesenteric vessels removed. Mesenteric vascular weight was measured and TGF-beta1 and alpha1 (type IV) collagen messenger (m)RNA levels were analysed by Northern analysis. Immunohistochemical analyses for TGF-beta1 and type IV collagen were also performed. RESULTS: The diabetic rats had increased mesenteric vessel weight at 3 weeks but not at 1 week and a concomitant rise in mesenteric TGF-beta1 and in alpha1 (type IV) collagen mRNA levels. Ramipril treatment attenuated mesenteric vessel hypertrophy and prevented the increase in TGF-beta1 and alpha1 (type IV) collagen mRNA levels after 3 weeks of diabetes. The immunohistochemical analysis revealed that diabetes was associated with increased TGF-beta1 and type IV collagen protein and extracellular matrix accumulation in mesenteric vessels, and this increase was reduced by ramipril treatment. CONCLUSIONS: These results support the concept that TGF-beta is involved in the changes associated with diabetic vascular disease, and suggest a mechanism by which angiotensin converting enzyme inhibitors exert their antitrophic effects.     

Serotonin enhances the production of type IV collagen by human mesangial cells

BACKGROUND: The plasma concentration of 5-hydroxytryptamine (5-HT) in diabetic patients is higher than that in normal subjects. Since recent reports have demonstrated the presence of 5-HT2A receptor in glomerular mesangial cells, it is possible that 5-HT may be involved in the development of diabetic nephropathy through the 5-HT2A receptor in mesangial cells. Because expansion of the glomerular mesangial lesion is a characteristic feature of diabetic nephropathy, we examined the effect of 5-HT on the production of type IV collagen by human mesangial cells. METHODS: Human mesangial cells were incubated with 5-HT with or without 5-HT receptor antagonists, protein kinase C (PKC) inhibitor or transforming growth factor-beta (TGF-beta) antibody. Type IV collagen mRNA and protein concentration in medium were measured by Northern blot analysis and enzyme-linked immunosorbent assay (ELISA), respectively. TGF-beta mRNA and bioactivity in the medium were measured by Northern blot analysis and bioassay using mink lung epithelial cells, respectively. RESULTS: 5-HT stimulated the production of type IV collagen by human mesangial cells, which was inhibited by ketanserin and sarpogrelate hydrochloride, 5-HT2A receptor antagonists, but not by ondansetron, a 5-HT3 receptor antagonist. 5-HT increased the bioactivities of both active and total TGF-beta. However, the 5-HT-enhanced production of type IV collagen was completely inhibited by an anti-TGF-beta antibody. Furthermore, a PKC inhibitor, calphostin C, inhibited the 5-HT-induced increase in type IV collagen secretion, and the activity of membrane PKC was increased by 5-HT. Phorbol ester activated type IV collagen production as well as active and total TGF-beta. Calphostin C completely inhibited the 5-HT-enhanced activity of active TGF-beta, but did not inhibit exogenous TGF-beta-induced increase in type IV collagen secretion. CONCLUSIONS: Our results suggest that 5-HT-enhanced production of type IV collagen by human mesangial cells is mediated by activation of PKC and subsequent increase in active TGF-beta activity.     

Quantitative structure activity relationship for the effect of benzoic acids, cinnamic acids and benzaldehydes on Listeria monocytogenes

We characterized the lymphocytes in the tarsal joint synovium of chickens inoculated with an arthrotropic strain of avian reovirus. Cryostat sections of whole joints taken from 2 days to 35 days postinoculation were analyzed using monoclonal antibodies directed against B lymphocytes, T lymphocytes, and chicken Ia antigen. Plasma cells were morphologically identified using stained sections of whole joints. Time-dependent changes were found in the type and number of positively staining cells. Synoviocytes and cells with a dendritic morphology stained positive for Ia in normal joint sections. T cells, mostly CD8 positive, were present in low numbers in acute phase arthritis (2-6 days postinfection) in the perivascular and superficial regions of the synovium. Subacute arthritis (8-14 days postinfection) was characterized by increased numbers of CD4 and Cd8 T cells in the perivascular and superficial regions. The perivascular T cells began to organize into aggregates, with IgM-positive B cells and plasma cells on the periphery of these aggregates. Some CD8-positive cells were detected on the surface of the articular cartilage. Cells staining positively for Ia were not lymphocytes. Chronic arthritis ( > 14 days postinfection) was characterized by large numbers of T cells in the perivascular and superficial regions, with the CD4-positive T cells found primarily in the lymphoid aggregates of the perivascular regions. IgM-positive B cells were fewer, but more plasma cells, few of which stained positive for IgM, were present. Lymphocytes in chronic arthritis stained positively for Ia. These data suggest that the types, numbers, and activation level of lymphocytes present in the tarsal joints are similar but not identical to those seen in rheumatoid arthritis.     

Immunohistochemical detection of K-sam protein in stomach cancer

The K-sam gene, originally isolated as an amplified gene from the stomach cancer cell line KATO-III, is characterized by its preferential amplification in the undifferentiated type (diffuse type) of stomach cancer and encodes one of the receptors for heparin-binding growth factors or fibroblast growth factors. The K-sam gene has been isolated by different methods and has been designated BEK, TK14, and Cek2. The receptor for keratinocyte growth factor was also found to be encoded by the same gene. To examine the expression of the K-sam protein in stomach cancer, polyclonal antibody pK1-2 was raised against the extracellular domain of the gene product. This antibody detected K-sam proteins by Western blot and flow cytometry analyses in stomach cancer cell lines KATO-III and HSC39, in which the K-sam gene is amplified and overexpressed. By immunohistochemical analysis, 20 of 38 cases of the undifferentiated type of advanced stomach cancer were K-sam positive, whereas none of 11 cases of the differentiated or intestinal type revealed K-sam staining. The K-sam product was observed predominantly in diffusely infiltrative lesions. In one autopsy case, the K-sam protein was detected only focally in the primary tumor, whereas markedly increased staining for the K-sam product was detected diffusely in the metastasized tumor in the lymph node and liver. These results suggest that K-sam overexpression is associated with the malignant phenotype of the undifferentiated type of stomach cancer, such as infiltrative growth and metastasis.     

Methods in the evaluation of medical students]

BACKGROUND: Delayed diagnosis, a high rate of histologically undifferentiated types of tumors, and rapid disease progression are frequently cited as the main reasons for the poor prognosis of gastric cancer in young patients. An improved prognosis has been anticipated for young gastric cancer patients because of recent improvements in digestive tract diagnostic techniques. This retrospective study was designed to determine whether these trends have had an impact on young Japanese patients with gastric cancer, and to further elucidate differences in clinicopathologic features between elderly and young patients. METHODS: From 1984 to 1995, 1654 patients with gastric cancer were admitted to our hospital. Of these, 86 patients (5.2%) were less than 40 years of age (young group). The clinicopathologic features of this young group were reviewed retrospectively, using hospital records, and compared with those of older patients (n = 499 [29.4%], 60 to 69 years of age). RESULTS: The young group contained significantly higher percentages of female patients, epigastric pain symptoms, depressed superficial type lesions, mucosal invasion, and poorly differentiated histology; percentages of hepatic metastasis and venous invasion were lower. Survival rates for all patients and for the resected cases were significantly better in the young group (p = 0.035 and 0.017 respectively). The percentage of early stage stomach cancers for the group less than 40 years of age was 49.0% in 1984-89, but had risen to 60.9% by 1990-95. CONCLUSIONS: Early diagnosis has improved the prognosis of young gastric cancer patients. Furthermore, these data show a recent shift in stage distribution; additional prognostic improvement is anticipated for young patients with early gastric cancer.     

Distribution of the alpha1 to alpha6 chains of type IV collagen in bovine follicles

During follicular development the proliferative and differentiated state of the epithelioid granulosa cells changes, and the movement of fluid across the follicular basal lamina enables the formation of an antrum. Type IV collagen is an important component of many basal laminae. Each molecule is composed of three alpha chains; however, six different type IV collagen chains have been identified. It is not known which of these chains are present in the follicular basal lamina and whether the type IV collagen composition of the basal lamina changes during follicular development. Therefore, we immunolocalized each of the six chains in bovine ovaries using antibodies directed to the nonconserved non-collagenous (NC) domains. Additionally, dissected follicles were digested with collagenase to release the NC domains, and the NC1 domains were then detected by standard Western immunoblot methods. The follicular basal lamina of almost all primordial and preantral follicles was positive for all type IV collagen alpha chains. Colocalization of type IV collagen and factor VIII-related antigen allowed for discrimination between the follicular and endothelial basal laminae. Type IV collagen alpha1, alpha2, alpha3, alpha4, and alpha5 chains were present within the follicular basal lamina of only a proportion of antral follicles (17 of 22, 20 of 21, 15 of 18, 14 of 28, and 12 of 23, respectively), and staining was less intense than in the preantral follicles. Staining for the alpha1 and alpha2 chains was diffusely distributed throughout the theca in regions not associated with recognized basal laminae. The specificity of this immunostaining for alpha1 and alpha2 chains of type IV collagen was confirmed by Western immunoblots. As well as being detected in the basal lamina of approximately half of the antral follicles examined, type IV collagen alpha4 also colocalized with 3beta-hydroxysteroid dehydrogenase-immunopositive cells in the theca interna. Type IV collagen alpha6 was detected in the basal lamina of only one of the 16 antral follicles examined. Thus, the follicular basal lamina changes in composition during follicular development, with immunostaining levels being reduced for all type IV collagen chains and immunoreactivity for type IV collagen alpha6 being lost as follicle size increases. Additionally, immunoreactivity for alpha1 and alpha2 appears in the extracellular matrix of the theca as it develops.     

Use of a life events calendar approach to elicit occupational history from farmers

BACKGROUND: The usefulness of and problems associated with an ultrasound catheter probe in the pretreatment staging of endoscopically early gastric cancer remain unexplored. METHODS: Endoscopic ultrasonography using a 15 MHz catheter probe of 2.6 mm diameter was performed in a prospective study to determine the pretherapy staging of endoscopically early gastric cancer in 78 patients. The results of the ultrasound images were compared with the histologic findings of the specimens obtained by endoscopic mucosal resection or surgical resection. RESULTS: The accuracy of the catheter probe for depth of invasion of endoscopically early gastric cancers was 67% (52 of 78 patients). The accuracy in determining depth of invasion in relation to endoscopic type was significantly higher for the elevated type (91%) than for the depressed type of early cancer (56%) (p < 0.01). The staging accuracy classified by histologic type was significantly higher for differentiated (86%) than for undifferentiated (18%) cancer (p < 0.01). Staging accuracy decreased as tumor size increased. The accuracy, sensitivity, and specificity for nodal staging were 80%, 17%, and 90%, respectively. CONCLUSIONS: A 15 MHz ultrasound catheter probe is most useful for determining depth of invasion when the tumor is histologically differentiated and endoscopically of the small elevated type early gastric cancer, but it is unreliable in the diagnosis of metastatic lymph nodes.     

Decreased type IV collagen expression by human decidual tissues in spontaneous abortion

To provide some insight into the etiology of spontaneous abortion, the expression of type IV collagen was investigated in human decidual tissues obtained after spontaneous abortion (n = 17) and normal pregnancy (n = 22). Indirect immunofluorescent staining was performed for type I, III, and IV collagen as well as laminin, and Northern blot analysis was conducted to assess the expression of messenger ribonucleic acid for the alpha 1(IV) chain. Immunohistochemical analysis did not reveal any significant differences between normal pregnancy and spontaneous abortion with respect to interstitial collagens (type I and III collagen) and laminin in the decidual tissue. However, although pericellular immunostaining for type IV collagen was recognized around the decidual cells in normal pregnancy, very weak or no staining was observed in spontaneous abortion. Northern blot analysis revealed that the decidual expression of messenger ribonucleic acid for the alpha 1(IV) chain was significantly reduced in spontaneous abortion compared to that in normal pregnancy (P < 0.001). These results suggest that type IV collagen might play an important role in the maintenance of pregnancy and that decreased expression of this collagen could be associated with spontaneous abortion.     

Effect of cytochalasin D on articular cartilage cell phenotype and shape in long-term organ culture

It has been documented, on the basis of cell culture experiments, that cytochalasin treatment promotes a round cell shape in chondroblast cultures by altering the cytoskeleton, and that it simultaneously alters the balance between production of type I and type II collagens. The aim in this study was to monitor the deposition of pro-type-I and type II collagens, and possible changes in articular cartilage layers in the mandibular condyle of the mouse under the influence of Cytochalasin D (CD) when total craniomandibular joints of 5-day-old mice were cultured in one block. The experimental group comprised 20 Balb/c mice of both sexes. Twenty in vitro controls were cultured without the administration of cytochalasin. The mice in the third group were used as in vivo controls. The cells in the prechondroblast layer responded with a rapid change in shape when treated with CD and assumed a rounded morphology. The total thickness of the cell layer was reduced at 7 days. Immunostaining against pro-type-I collagen was intense in the narrow fibrous and prechondroblast layers in the CD-treated group, whereas the stained area was wider and the staining gradually reduced in the deeper cartilage layers in the in vitro controls. Staining against type II collagen became weaker at the end of the culturing period of the CD-treated group, whereas in the in vitro controls the staining against type II collagen was clearly visible at all observation times. These phenomena can be explained by changes in differentiation and the altered cell cycle of the chondroblasts in organ culture under the influence of CD.     

p53 protein overexpression as a predictor of the response to chemotherapy in gastric cancer

This study was performed to evaluate p53 overexpression as a predictor of the response to chemotherapy of patients with gastric cancer. The subjects comprised 20 patients with Stage IV gastric cancer and three with locally recurrent lesions, all of whom were treated with 5-fluorouracil (5-FU) plus cisplatin (CDDP) for 4 weeks. Of the total 23 patients there were 10 responders; 2 showing complete response (CR) and 8, partial response (PR). Specimens obtained by endoscopic biopsy were immunohistochemically stained using anti-p53 protein and bcl-2 protein antibody. Of the 10 responders, 7 demonstrated negative p53 staining, and of the 13 nonresponders, 11 demonstrated positive p53 staining (P = 0.013). Tissue from 3 of the responders and 7 of the nonresponders that stained for bcl-2 were positive prior to chemotherapy; however, there was no association between bcl-2 staining and chemotherapeutic effect. In conclusion, immunohistochemical identification of p53 in pretreatment tissue may represent a useful predictor for chemotherapeutic outcome in patients with gastric cancer.     

Intra-operative diagnosis of N2 lymph node metastasis of gastric cancer

BACKGROUND/AIMS: Limited lymph node dissection for gastric cancer, which is prevalent in Western countries, leaves cancer cells in the second tier of nodes in patients who have metastasis in those nodes. It is, however, difficult to correctly diagnose nodal status during surgery. The present study was, therefore, designed to examine how to detect N2 metastasis intra-operatively. METHODOLOGY: Five hundred and eight patients undergoing extended lymph node dissections for gastric cancer were retrospectively analyzed. Accuracy of the intraoperative diagnosis of node involvement based on macroscopic findings was investigated, according to the N stage and histological type of the tumor. Furthermore, the distributions of N2 metastasis were clarified, according to tumor site. RESULTS: Intra-operative macroscopic findings were frequently assessed as being less severe than histological findings in cases with N2 metastasis (61.9%, 39/63). Intra-operative recognition of N2 metastasis was significantly lower in the cases with undifferentiated adenocarcinoma (28.2%, 11/39) than in those with differentiated adenocarcinoma (56.5%, 13/23). The distributions of N2 metastasis revealed nodes along the left gastric and common hepatic arteries to be the key junctions for lymphatic flow from the middle and lower thirds of the stomach, respectively. CONCLUSIONS: Intra-operative diagnosis of N2 metastasis is difficult to make based on macroscopic findings, especially in undifferentiated tumors. To detect N2 metastasis intra-operatively, the nodes along the left gastric or common hepatic artery should be submitted to frozen section examination for primary tumors located in the middle or lower third of the stomach, respectively.