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ABSTRACT: Although malignant diseases are known to be associated with immune suppression, detailed mechanisms of this phenomenon are still unknown. NKG2D is an activating cell surface receptor expressed by natural killer (NK) cells and CD8+ T cells, and it has been reported that NKG2D engagement is extremely important for T cell activation. In the current study, NKG2D expression on CD8+ T cells and the frequency of CD4+ CD25+ regulatory T (Treg) cells were determined by multicolor flow cytometry to investigate one of the mechanisms responsible for immune evasion in esophageal cancer patients. NKG2D expression on CD8+ T lymphocytes in esophageal cancer patients was significantly lower than in those of normal controls. NKG2D expression in T3/T4 esophageal cancer was significantly lower than that in T1/T2 esophageal cancer. CD8+ T cells from patients with lymph node metastasis expressed significantly lower NKG2D than those without lymph node metastasis. Moreover, significantly lower NKG2D expression was observed in stage III/IV cancer in comparison with stage I/II. The frequency of CD4+CD25+ Treg cells in esophageal cancer patients was significantly higher than those in normal controls. NKG2D expression on CD8+ T cells was significantly inversely correlated with the frequency of CD4+CD25+ Treg cells in esophageal cancer patients. Our data indicates that decreased NKG2D expression on CD8+ T cells is correlated with disease severity. Decreased NKG2D expression and an increase in Treg cells may be one of the key mechanisms responsible for immune evasion in esophageal cancer.
Diseases of the Esophagus 07/2008; 22(1):49-54. · 1.81 Impact Factor
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ABSTRACT: To understand the efficacy of gastrectomy combined with the resection of other organs and to refine the indications for this type of surgery, the records of 156 patients with carcinoma of the stomach directly invading adjacent organs or structures (T4 gastric carcinoma) were analyzed retrospectively.
The patients were divided into three groups, as follows: in group A, curative resection was performed by the combined resection of invaded organs or structures; in group B, although combined resection was performed, curative resection could not be performed because of the extent of lymph node metastasis, liver metastasis, and/or peritoneal metastasis; in group C, combined resection was not performed.
In patients with peritoneal or liver metastasis, there was no significant difference in prognosis among the three groups. In patients without peritoneal and liver metastasis, the prognosis of group A was significantly better than that of group B or group C, irrespective of the extent of lymph node metastasis or the number of invaded organs. In these group A patients, the 5-year survival rates of those with localized tumors and no lymph node metastasis, those with localized tumors and lymph node metastasis, those with infiltrating tumors and no lymph node metastasis, and those with infiltrating tumors and lymph node metastasis were 100%, 56.2%, 57.1%, and 13.6%, respectively.
Combined resection of involved organs should be carried out with curative intent in patients with localized gastric cancer or infiltrating gastric cancer without lymph node metastasis.
Gastric Cancer 02/2001; 4(4):206-11. · 2.42 Impact Factor
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ABSTRACT: The accumulation of mutated p53 in tumor cells results in the presence in the circulation of mutant p53 (p53m) and the production of p53-specific antibodies (p53Ab). We examined the relationships among these phenomena and analyzed their clinical implications in 62 patients with gastric cancer at various stages. Expression of p53 in tumors was studied by an immunohistochemical method and circulating p53m and p53Ab were quantitated with commercially available enzyme-linked immunosorbent assay kits. The detectable expression of p53 in tumors and circulating p53Ab was recognized in 28 (45.2%) and 7 (11.3%) of the 62 patients, respectively. The number of patients with higher levels of circulating p53m increased with the progression of the depth of cancer invasion. Patients with any positive findings for the three p53-related parameters had a poorer prognosis, and the difference was statistically significant in patients with p53Ab. When survival was analyzed in terms of the combination of the three p53-related parameters (detectable expression of p53 in tumor cells, high levels of p53m and p53Ab in the circulation), a significantly poorer prognosis was associated with an increase in the number of positive parameters. Analysis of p53 in tumor cells, together with analysis of circulating p53m and p53Ab, could improve the accuracy of prognosis in patients with gastric cancer.
Journal of experimental & clinical cancer research: CR 01/2001; 19(4):489-95. · 1.50 Impact Factor
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ABSTRACT: Transforming growth factors beta (TGFs beta) are involved in a variety of important cellular functions, including cell growth and differentiation, adhesion, migration, extracellular matrix formation, and immune function. Moreover, it has been reported that TGFs beta are correlated with angiogenesis. However, the role of TGF-beta as an angiogenic factor in gastric carcinoma is still unclear.
TGF-beta1 expression was determined in 101 patients with gastric carcinoma by immunohistochemical procedures, and this expression was compared in the current study with both the expression of vascular endothelial growth factor (VEGF), which is thought to be the most potent angiogenic factor, and microvessel density, to evaluate the effect of TGF-beta1 on the angiogenesis of gastric carcinoma tissues.
TGF-beta1 expression was detected in 23 tumors (22.8%). TGF-beta1 expression was more frequent in differentiated than in undifferentiated gastric carcinoma. Furthermore, TGF-beta1 expression was significantly correlated with the depth of invasion and the stage of disease. There was a close correlation between TGF-beta1 expression and VEGF expression. There was no correlation between TGF-beta1 expression and microvessel density, whereas VEGF expression was significantly correlated with microvessel density. With regard to prognosis, the 5-year survival rate was 55.9% for patients with TGF-beta1 positive tumors and 67.0% in patients with TGF-beta1 negative tumors. Accordingly, the prognosis for patients with TGF-beta1 negative tumors was significantly better than that for patients with TGF-beta1 positive tumors. Multivariate analysis indicated that lymph node metastasis, tumor size, and TGF-beta1 expression were independent prognostic factors.
These results suggest that TGF-beta1 might be associated with tumor progression by indirectly stimulating angiogenesis through the up-regulation of VEGF expression in gastric carcinoma.
Cancer 11/1999; 86(8):1455-62. · 4.77 Impact Factor
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ABSTRACT: The expression of thymidine phosphorylase (TP) and the density of microvessel in advanced gastric carcinoma were examined by immunohistochemistry to evaluate the significance of TP. The expression of TP was negative in 72 cases, positive in 54. The microvessel density correlated with the expression of TP. In total cases, patients with TP-positive tumours survived longer than those with TP-negative tumours. In patients treated with fluorouracil derivatives (FUs), the expression of TP significantly correlated with favourable prognosis and with unfavourable prognosis in those not treated with FUs. The patients with TP-positive tumours, the prognosis of patients treated with FUs was significantly better than that of those not treated with FUs. In patients with TP-positive tumours, treatment with FUs and lymph node metastasis were independent prognostic factors according to the Cox proportional hazards model. Depth of invasion and lymph node metastasis were independent prognostic factors in patients with TP-negative tumours. The determination of the expression of TP might be useful for predicting the efficacy of post-operative chemotherapy using FUs to prevent recurrence in advanced gastric carcinoma patients who undergo curative gastrectomy.
British Journal of Cancer 11/1999; 81(3):484-9. · 5.04 Impact Factor
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ABSTRACT: An animal model of intraperitoneal (i.p.) cisplatin chemotherapy using hypotonic solutions of sodium chloride has been developed as a treatment for peritoneal carcinomatosis. The concentrations of platinum in the plasma and in the i.p. fluid of Donryu rats were measured after i.p. injection of hypotonic (103 or 154 mosm/l) and isotonic (308 mosm/l) solutions that contained an equal amount of cisplatin. The maximum concentration (Cmax) and the area under the curve of concentration versus time (AUC) of platinum in the plasma increased proportionately with increases in the dose of cisplatin and they were significantly higher in rats given cisplatin in hypotonic solutions than in those given the drug in isotonic solution. The Cmax and AUC of total platinum were similar for the solution of 103 mosm/l with 2.5 mg/kg cisplatin and the isotonic solution with 5.0 mg/kg cisplatin. The Cmax and AUC of free platinum in the plasma did not increase with increases in the dose of cisplatin in isotonic solution but did increase after hypotonic injection. However, the solutions of lower osmolarity gave a decreased AUC of platinum in the i.p. fluid. Hypotonic conditions continued for 30 min at most after i.p. injection of hypotonic solutions. When the same dose of cisplatin was given to rats with tumors derived from AH100B carcinoma cells, the amount of platinum taken by i.p. solid tumors from the solution of 103 mosm/l was about twice that from the isotonic solution and was much the same as that taken up from the isotonic solution with twice the amount of cisplatin. These results indicate that hypotonic i.p. cisplatin chemotherapy might be preferable to escalation of the dose of i.p. cisplatin in the treatment of peritoneal carcinomatosis.
Oncology 08/1999; 57(1):77-82. · 2.27 Impact Factor
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ABSTRACT: Vascular endothelial growth factor (VEGF) is one of the most important factors for angiogenesis in various malignant tumors. However, the clinicopathological and biological significance of the expression of VEGF in gastric cancer remains unclear. In this study, we investigated the relationship between the expression of VEGF and the clinicopathological and biological status of advanced gastric cancer, all of the same stage.
The expression of VEGF was immunohistochemically examined using the polyclonal antibody A-20 in tumors from 97 patients with invasion of the serosa but no lymph-node metastasis (t3, n0, stage II). The results were compared with clinicopathological and biological status (microvessel density and proliferative activity) of tumors.
Expression of VEGF was detected in 27 of 97 tumors (28%). The mean microvessel density (MVD) of 27 VEGF-positive tumors (458/mm2) was higher than that of 70 VEGF-negative tumors (331/mm2, P=0.0001). However, the proliferative activity expressed as the Ki-67 labeling index (LI; percentage of immunostained cancer cells) of 27 VEGF-positive tumors (13.8%) was significantly lower than that of 70 VEGF-negative tumors (26.7%, P=0.0002). In 48 tumors with low proliferative activity of cancer cells (Ki-67 LI < or =18%), 20 (42%) tumors expressed VEGF, and these tumors had a high MVD (4461/mm2). In the 93 surviving patients, the 5-year survival rate of the 25 patients with VEGF-positive tumors (64%) was not different from that of the 68 patients with VEGF-negative tumors (73%, P=0.4296).
Advanced gastric carcinoma with low proliferative activity may produce VEGF and may have high angiogenic potential in order for the tumor itself to grow. However, the prognosis of patients with such tumors was not unfavorable.
Langenbeck s Archives of Surgery 07/1999; 384(3):264-70. · 1.81 Impact Factor
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ABSTRACT: Increased levels of a soluble receptor for interleukin-2 (sIL-2R) have been found in the serum from patients with a variety of malignancies. Levels of sIL-2R have not previously been examined in a large group of patients with gastric cancer as a possible indicator of prognosis. Serum levels of sIL-2R were measured preoperatively by an enzyme-linked immunosorbent assay in 121 patients with gastric cancer. The preoperative levels of sIL-2R in patients with gastric cancer were significantly higher than those in normal controls. An elevated level of sIL-2R was significantly correlated with certain clinicopathologic features, which included depth of invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion and clinical stage. The postoperative survival time of patients with elevated levels of sIL-2R was significantly shorter than that of patients with normal levels. Furthermore, a multivariate analysis using Cox's proportional hazards model showed that the combination of levels of carcinoembryonic antigen and sIL-2R was an independent indicator of prognosis. Thus, the serum level of sIL-2R might be a useful prognostic indicator in patients with gastric cancer.
Oncology 05/1999; 56(3):253-8. · 2.27 Impact Factor
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ABSTRACT: Japanese surgeons have been actively performing extended lymphadenectomy (D2, removal of perigastric nodes and nodes along the left gastric, common hepatic, celiac and splenic arteries; or D3, D2 plus removal of nodes in the hepatoduodenal ligament, in the retropancreatic space and along the vessels of the transverse mesocolon). In recent years interest has expanded to superextended lymphadenectomy (D4) of nodes around abdominal aorta (para-aortic lymph nodes from aortic hiatus to aortic bifurcation). Because the therapeutic value of this D4 procedure remains controversial, we initiated a prospective study to compare D3 and D4 lymphadenectomy.
Seventy patients with T3 or T4 gastric cancer and without macroscopic metastasis to the para-aortic nodes treated by potentially curative total gastrectomy were randomized to D4 (group A, n = 35) and D3 (group B, n = 35) lymphadenectomies.
Metastases to para-aortic nodes were found in 4 patients. Postoperative survival after D4 resection was not statistically significant between the groups. Postoperative morbidity for group A was greater. In group A 4 patients had postoperative retention of intra-abdominal fluid (lymphorrhea) and 4 others had prolonged diarrhea. One patient in each group died of postoperative complications.
Surgical treatment of microscopic disease in grossly normal para-aortic lymph nodes may generate occasional long-term survivors. Selecting appropriate candidates who might benefit from D4 resections needs to be refined. On the basis of this study, a nationwide study should be considered.
Surgery 04/1999; 125(3):325-31. · 3.10 Impact Factor
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ABSTRACT: Less invasive treatment is the current trend in many surgical fields. Most patients with early gastric cancer do not have lymph node metastasis. Thus extensive resection of the stomach and extended lymph node dissection do not appear to be necessary.
In a retrospective study, 890 consecutive patients with early gastric cancer who had undergone standard gastrectomy were assessed for depth of invasion, gross appearance, and maximum diameter of the tumor to examine the possibility of limiting the extent of lymph node dissection. A variety of limited gastrectomies have been developed and now include endoscopic mucosal resection, wedge resection, segmental gastrectomy, limited proximal gastrectomy, and distal hemigastrectomy.
A retrospective study revealed that extensive lymph node dissection did not improve the survival of patients with early gastric cancer. Endoscopic mucosal resection was suitable for cancers of the depressed type of less than 1 cm in diameter and the elevated type of less than 2 cm in diameter. Wedge, segmental, or limited proximal gastrectomy was suitable for the elevated type of 2 to 3 cm in diameter. The elevated type of more than 3 cm in diameter and the depressed type of 1 to 3 cm in diameter sometimes involved metastasis to group 1 nodes. The depressed type of more than 3 cm in diameter sometimes involved metastasis to group 2 nodes. Thus such cases should be treated by gastrectomy with dissection of potentially metastatic lymph nodes.
Limitation of the extent of gastrectomy and lymph node dissection may be possible, depending on the gross appearance and size of the tumor.
Surgery 03/1999; 125(2):148-54. · 3.10 Impact Factor
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ABSTRACT: It has recently been reported that the microvessel density in a tumor correlates with hematogenous metastasis in gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of vascular endothelial growth factor (VEGF), which was thought to be a potent angiogenesis-promoting factor, and hematogenous recurrence in advanced gastric carcinoma.
The expression of VEGF and the density of the microvessels were examined by immunohistochemistry in patients with advanced gastric carcinoma with serosal invasion who had undergone curative resection.
The prognosis of patients with a VEGF-negative tumor was significantly better than that of patients with a VEGF-positive tumor. Multivariate analysis by Cox proportional hazards model showed that the expression of VEGF was an independent prognostic indicator. The expression of VEGF provided a significant estimate of relative risk for the development of hematogenous recurrence by multivariate logistic regression analysis. The microvessel count in VEGF-positive tumors was significantly higher than that in VEGF-negative tumors.
VEGF is associated with hematogenous recurrence. Assessment of the expression of VEGF may therefore prove valuable in identifying patients with gastric carcinoma at high risk for recurrence who would benefit from adjuvant therapy.
Surgery 03/1999; 125(2):195-201. · 3.10 Impact Factor
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ABSTRACT: Recent studies have shown that tumor suppressor genes, particularly p53, may play a crucial regulatory role in the control of angiogenesis. Accordingly, we analyzed the correlation between p53 accumulation and the expression of vascular endothelial growth factor (VEGF) and microvessel counts in a series of human gastric adenocarcinomas by immunohistochemical staining. p53 expression was absent in 35 cases (29.7%), weak in 34 cases (28.8%), moderate in 35 cases (29.7%), and strong in 14 cases (11.8%). The prognosis of patients with both absent and weak expression of p53 was significantly better than that of patients with both moderate and strong expression of p53. VEGF expression was significantly associated with increased p53 expression. Moreover, increasing expression of p53 significantly correlated with an increase in microvessel counts. Nuclear p53 accumulation may correlate with tumor angiogenesis through VEGF upregulation in gastric carcinomas.
Oncology 02/1999; 57(2):164-72. · 2.27 Impact Factor
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ABSTRACT: To evaluate the correlation between the morphologic nuclear features and clinicopathologic parameters in patients with advanced gastric cancer.
Nuclear profiles have been reported as useful prognostic predictors in various cancers. Data from computerized morphometries are objective and quickly derived using conventional microscopic analysis. However, this image analysis of nuclear features has rarely been applied to investigations of gastric adenocarcinoma. Moreover, it remains to be shown what types of biologic factors influence the nuclear features.
Morphometric nuclear features (nuclear area, perimeter, and shape) were analyzed in 202 patients with serosal-invaded gastric cancer (stage II and III) who underwent curative gastrectomy. In each case, 300 cancer nuclei were analyzed on routine hematoxylin and eosin-stained slides through the use of a computer-assisted image analysis system by tracing the nuclear profiles (magnification x400) on a computer monitor. The morphometric data were compared with patient survival, clinicopathologic status, DNA ploidy pattern of tumors, expression of p53 protein, and proliferative activity of cancer cells.
Lymph node metastasis, lymphatic invasion, and venous invasion were more frequently detected in patients with large nuclear areas. Significant correlations were detected between the size of the nuclear area of cancer cells and the biologic factors of tumors, such as expression of p53, Ki-67 labeling index, and DNA ploidy pattern. The 5-year survival rate of the 100 patients in the large-nuclear group (nuclear area >45.3 microm2) was 47.6% and was significantly lower than the 74.4% rate of the 98 patients in the small-nuclear group (nuclear area < or =45.3 microm2). Moreover, the nuclear area was found to be an independent prognostic factor in the multivariate analysis.
Gastric cancer cells with a large nuclear area express mutated p53 protein and have high proliferative activity. Moreover, such cancer cells have high potential for invasion to the microvessels in the gastric wall. Thus, nuclear morphometry is a new and useful morphologic predictor for metastatic potential in advanced gastric cancer.
Annals of Surgery 02/1999; 229(1):55-61. · 7.49 Impact Factor
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ABSTRACT: In this study, we obtained fresh samples of tissue (tumors, adjacent normal mucosas, and metastatic lymph nodes) from 64 patients (metastatic lymph nodes were obtained from 16 patients) with esophageal cancer who underwent esophagectomy between 1993 and 1998. The thymidine phosphorylase (dThdPase) levels of tumors as determined by the ELISA method were compared with clinicopathological findings of tumors and were evaluated for their usefulness as a prognostic parameter for these patients. The dThdPase levels of tumors (221 +/- 21 U/mg protein) and metastatic lymph nodes (253 +/- 51 U/mg protein) were significantly higher than the dThdPase level of normal mucosas (53 +/- 7 U/mg protein, p < 0. 001). The dThdPase levels of tumors did not correlate with the histopathological grading of tumors, the depth of tumor invasion, and lymph node metastasis. The 3-year survival rate of 32 patients with a high level of dThdPase (42%) was not different from that of 32 patients with a low level of dThdPase (52%, p = 0.267). Moreover, the dThdPase level of tumors was not an independent prognostic factor for patients with esophageal cancer. These findings suggest that the level of dThdPase activity in esophageal cancers may not correlate with tumor progression and may not be a useful prognostic marker for patients with esophageal squamous cell carcinoma.
European Surgical Research 02/1999; 31(4):357-63. · 0.93 Impact Factor
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ABSTRACT: It has been reported that decreased numbers of dendritic cells (DCs) are correlated with poor prognosis in some types of malignancy, such as gastric cancer. However, factors that determine the density of DCs have not been characterized. It was recently reported that vascular endothelial growth factor (VEGF) inhibits the functional maturation of DCs from CD34+ precursors. In this study, we analysed the relationship between the expression of VEGF and the density of DCs in gastric carcinoma tissues by immunohistochemical staining. The extent of infiltration by DCs was graded from marked to slight on the basis of the mean densities of DCs. The prognosis of patients with marked infiltration was significantly better than that of patients with slight infiltration among patients who had undergone curative resection. Multivariate analysis showed that infiltration by DCs was an independent prognostic indicator. Furthermore, there was an inverse correlation between the density of DCs and the expression of VEGF Our results suggest that expression of VEGF might be associated with tumour progression and poor prognosis not only because VEGF stimulates angiogenesis, but also because it allows tumours to escape from attack by the immune system in patients with gastric carcinoma.
British Journal of Cancer 01/1999; 78(12):1573-7. · 5.04 Impact Factor
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ABSTRACT: The expression of variant isoforms of CD44 is correlated with the ability of tumor cells to metastasize in some clinical carcinomas. In this study, the serum concentration of soluble splice isoforms of CD44 that shared exon variant 6 (sCD44v6) were measured and the histologic expression of CD44v6 in tumors from patients with gastric carcinoma examined.
Serum samples were obtained from 102 patients with primary gastric carcinoma before surgery and serum levels of sCD44v6 were determined with an enzyme-linked immunoadsorbent assay. The expression of CD44v6 in tumors was examined by immunohistochemical staining.
Both the serum concentration of sCD44v6 and its expression in tumors were associated significantly with the depth of invasion of the tumor, lymph node metastasis, and clinical stage in patients with diffuse type gastric carcinoma. Among patients with gastric carcinoma, the serum level of sCD44v6 was higher in those with CD44v6 positive tumor cells than in those with CD44v6 negative tumor cells. The serum level of sCD44v6 was a prognostic indicator in patients with diffuse type gastric carcinoma, as was the histologic expression of CD44v6. However, neither CD44v6 nor sCD44v6 was a predictor of survival time in patients with intestinal type gastric carcinoma.
It appears that CD44v6 and sCD44v6 are related to the progression of diffuse type gastric carcinoma. An elevated serum level of sCD44v6 may be useful as a prognostic indicator in patients with diffuse type gastric carcinoma.
Cancer 10/1998; 83(6):1094-101. · 4.77 Impact Factor
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ABSTRACT: To evaluate whether the expression of p53 and that of p21 are independent prognostic factors in patients with advanced gastric cancer, we investigated clinicopathological factors and the expression of p53 and p21 in 158 patients with gastric cancer that had invaded the serosa and who had undergone curative gastrectomy. In multivariate survival analysis of 156 surviving patients, we evaluated the size of the tumor, lymph node metastasis, venous invasion, lymph node dissection, expression of p53, and expression of p21 as independent prognostic factors. Moreover, we divided patients into four groups according to the expression of p53 and p21 in their tumors [group A, p53-/p21-, N = 40 (one died within 30 days of surgery); group B, p53-/p21+, N = 23; group C, p53+/p21-, N = 58; and group D, p53+/p21+, N = 37 (one died within 30 days of surgery)]. The 5- and 10-year survival rates of 39 patients in group A were 71.7% and 64.3%, those of 23 patients in group B were 81.4% and 81.4%, those of 58 patients in group C were 35.6% and 30.2%, and those of 36 patients in group D were 67.9% and 60.7%. The prognosis of patients in group C was poorer than that of patients in the other three groups. This result indicates that the evaluation of the expression of both p53 and p21 expression might provide prognostic information that is more accurate than that provided by evaluation of the expression of p53 alone.
Digestive Diseases and Sciences 06/1998; 43(5):964-70. · 2.12 Impact Factor
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ABSTRACT: Activated T lymphocytes release a soluble form of IL-2R (SoIL-2R) into the bloodstream, which can be detected by CD25 monoclonal antibody. Perioperative changes of serum levels of SoIL-2R and the number of CD25-positive cells were monitored simultaneously to clarify the clinical implications of SoIL-2R in patients with gastric cancer (n=91). Preoperative levels of SoIL-2R were significantly higher than in normal controls and levels were a useful indicator of possible lymph node involvement. Postoperative levels of SoIL-2R increased independently of the number of CD25-positive cells. Patients with progressive postoperative increases in levels of SoIL-2R had both a significantly high frequency of postoperative relapse and a poor prognosis. Increased SoIL-2R may reduce the availability of IL-2 by binding to it. Postoperative progressive increases in SoIL-2R appear to be a good indicator for a poor prognosis in patients with gastric cancer.
International Journal of Molecular Medicine 02/1998; 1(1):113-6. · 1.98 Impact Factor
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ABSTRACT: The preoperative levels of serum-soluble receptor for interleukin-2 (IL-2R) were determined by an enzyme-linked immunosorbent assay in 38 patients undergoing surgery for colorectal cancer and 98 healthy controls. The levels of serum-soluble IL-2R in the patients with colorectal cancer were significantly higher than those in the normal controls (P < 0.05). Markedly elevated levels of serum-soluble IL-2R were recognized in patients with stage IV cancer, those with Dukes' stage D cancer, and those with liver metastasis. Moreover, the prognosis of patients with low levels of IL-2R (<531 U/ml) was significantly better than that of those with high levels (P < 0.05). These findings demonstrate that an elevated concentration of soluble IL-2R might be a useful indicator of liver metastasis and poor prognosis in patients with colorectal carcinoma.
Surgery Today 01/1998; 28(10):1115-7. · 1.22 Impact Factor
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ABSTRACT: The aim of this study was to investigate the relation between the expression of mutated p53 protein and the proliferative activity of cancer cells in esophageal squamous cell carcinoma. In addition, the clinical and biologic significance of p53 status and the proliferative activity of cancer cells were evaluated in these patients.
Samples of esophageal tumors from 94 patients were subjected to immunohistochemical staining with a monoclonal antibody against p53 and with the monoclonal antibody Ki-67. The immunoreactivity against p53 and the proliferative activity of cancer cells were compared with the clinicopathologic findings in each sample. Prognostic factors including p53 status and Ki-67 labeling index (LI; percentage of Ki-67-immunostained cells) were evaluated for 81 surviving patients by univariate and multivariate analysis.
The mean Ki-67 LI of 50 p53-positive patients was higher than that of 44 p53-negative patients (p = 0.009). The Ki-67 LI increased according to the progression of tumors. Overexpression of mutated p53 protein was observed in 40.9% of tumors that invaded to the submucosa, and this percentage was not significantly changed in tumors with invasion to the adventitia. Metastases to the regional lymph nodes were observed in 3 of 22 patients with tumors that invaded to the submucosa, and these 3 tumors had both over-expression of mutated p53 protein and high Ki-67 LI. In 81 surviving patients, only lymph node metastasis (p = 0.045) and the curability of tumors (p < 0.001) were identified as independent prognostic factors by multivariate analysis.
Overexpression of mutated p53 protein is detected in the early stage of esophageal cancer. This mutated p53 protein may not play an important role for tumor invasion. When tumor invasion is limited to the submucosa, cancer cells that overexpress mutated p53 protein may acquire high proliferative activity. Such cells might have considerable potential for metastasis to the lymph nodes.
Journal of the American College of Surgeons 10/1997; 185(4):398-403. · 4.55 Impact Factor
