Daisuke Korenaga

Immunohistochemical expression of C-reactive protein in squamous cell carcinoma of the esophagus - significance as a tumor marker

C-reactive protein (CRP) is a prototype acute phase protein which has been known to be synthesized in hepatocytes. Although serum elevation of CRP has been reported to be an indicator of the unfavorable outcome of the patients in some malignant tumors, the expression of the protein in carcinoma cells has not been investigated. The aim of the current study was to assess the immunohistochemical expression of CRP in squamous cell carcinoma (SCC) of the esophagus and to find its biological significance. Immunohistochemical examination for CRP expression was performed for 37 advanced esophageal SCCs with the depth of T2, T3 or T4, which had been surgically resected without preoperative therapy for the patients. Eighteen carcinomas (48.6%) demonstrated immunohistochemical CRP expression. Univariate analysis showed that the prognosis of the patients with esophageal SCCs expressing CRP was significantly worse than that in patients with tumors without CRP expression (P=0.017). Moreover, CRP expression was found to be an independent prognosticator in patients with esophageal SCCs in the multivariate analysis (P=0.036). To the best of authors knowledge, this is the first report that demonstrated the possible carcinoma-related expression of CRP in SCCs of the esophagus and its biological significance as the prognosticator of the patients.

Overexpression of cyclin B1 in gastric cancer and its clinicopathological significance: an immunohistological study.

Abstractn Purpose. Cyclin B1 is a key regulator of progression through the G2/M transition during the cell cycle. Although cyclin B1 proteins are overexpressed in various types of human cancers, the relationship between cyclin B1 status in gastric cancer and its clinical significance remains unknown.n Methods. We examined cyclin B1 expression by immunohistological means in 61 patients with gastric cancer in terms of histological type, tumor invasion, and metastatic behavior. Specimens were considered positive when the cytoplasm of over 10% of the cancer cell population was stained.n Results. Cyclin B1 was overexpressed in 32 (53%) of 61 patients with gastric cancer. Tumors that expressed cyclin B1 were predominant in older patients, in well- and moderately differentiated adenocarcinomas and in expanding-growth type tumors. Conversely, expression of cyclin B1 was lower in poorly differentiated adenocarcinomas, and in those of the infiltrative growth type. Moreover, the disease was more advanced (stages III and IV) and widespread nodal involvement was more frequent when cyclin B1 expression was low. Logistic regression analyses showed that histological type is a significant factor related to cyclin B1 protein expression.n Conclusions. These findings suggested that cyclin B1 protein overexpression is closely associated with less aggressive tumor behavior. Therefore, G2/M cyclin alternatives and the possible role of cyclins in cancer development warrants further attention.

Fas ligand expression is correlated with metastasis in colorectal carcinoma

The Fas/Fas ligand (FasL) system is one apoptotic pathway through which malignant tumors can evade immune surveillance. While FasL is expressed in malignant tumors, Fas is conversely downregulated to escape host immune attack, resulting in tumor invasion. The aim of the current study was to find out further clinicopathological significance of FasL expression in carcinoma of the colon and rectum. FasL expression was investigated using immunohistochemical staining in 143 consecutive patients with primary colorectal carcinomas. Seventy-nine carcinomas (55.2%) expressed FasL. The incidence of lymph node and distant metastases in carcinomas expressing FasL was significantly higher than in carcinomas that did not express FasL (p = 0.031 and p = 0.0003, respectively). Although univariate analysis showed that survival in patients with carcinomas expressing FasL was significantly poorer than that in patients with carcinomas without FasL expression (p = 0.001), only Dukes’ stage was an independent prognosticator by multivariate analysis. FasL expression was found to be correlated with lymph node involvement and distant metastases in colorectal carcinoma.

The Effectiveness of Chemotherapy with Cisplatin and 5-Fluorouracil for Recurrent Small Cell Neuroendocrine Carcinoma of the Rectum: Report of a Case

We report herein the case of a 46-year-old-man with small cell neuroendocrine carcinoma (NEC) concomitant with large villous adenoma of the rectum, who underwent abdominaoperineal resection with regional lymphnode dissection. The resected specimen was histologically found to contain a small lesion of NEC confined to the submucosa in the large adenoma. A computed tomography scan done 4 months postoperatively revealed recurrences in the liver, lymph nodes, and bone. Therefore, two cycles of sequential intravenous combined chemotherapy with standard doses of cisplatin and 5-fluorouracil (5-FU) were administered, after which the size of each tumor decreased remarkably. Nevertheless, the patient died 8 months after the operation. As there was a fair response of this tumor to the combined chemotherapy of cisplatin and 5-FU, this regimen against NEC of the colon and rectum should be given consideration.

Smoking-related increase of O6-methylguanine-DNA methyltransferase expression in squamous cell carcinoma of the esophagus

DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) has a defensive role against alkylating agents associated with increased incidence of malignant tumors. The aim of the current study was to elucidate the significance of immunohistochemical expression of MGMT in squamous cell carcinoma (SCC) of the esophagus, with a special reference to the correlation of smoking. Immunohistostaining of MGMT was performed in the specimens collected from 100 patients with SCC of the esophagus. The relationship between the personal history of smoking and MGMT expression was examined and the value of Brinkman index was compared between patients with and without MGMT expression. Fifty-five SCCs (55.0%) had a positive response to MGMT inununostaining. The proportion of patients who had tumors with MGMT expression among patients with smoking habits was 62.0% (49 out of 79), which was significantly higher than that among patients without smoking habits (28.6%, 6 out of 21; P=0.005). The mean value of Brinkman index in patients who had tumors with MGMT expression (1189+/-604) was significantly higher than that in patients who had tumors without MGMT expression (871+/-656; P=0.020). Our results suggested that MGMT expression in esophageal SCC might be correlated with smoking habits of the patients.

Prognostic significance of serum superoxide dismutase activity in patients with gastric cancer.

Abstract.Background: Although superoxide dismutase (SOD) may play an important role in helping to protect against carcinogenesis or tumor progression, little information is available regarding the clinical evaluation of antioxidant defense in patients with gastric cancer.n Methods: Serum SOD activity in 34 patients with gastric cancer was estimated and the data compared with clinicopathological parameters.n Results: The mean serum SOD activity in the patients was 15.9% ± 2.6%, which was higher than the value obtained in healthy donors. The serum SOD activity in patients over 70 years of age was 14.5% ± 3.0%, which was significantly lower than the value of 16.6% ± 7.3% in those under 70 years of age (P < 0.01). According to the stage of disease, the reduction in SOD activity in the patients aged over 70 years was significant in those with far advanced tumor, classified as stage IV (P < 0.01), but not in those with stage I–III disease. When the cutoff value for high- and low-SOD groups was determined as 18.0%, based on the median value for serum SOD activity in 15 patients with stage IV gastric cancer, the survival rate of patients with stage IV tumor was significantly higher in the high-SOD group than in the low-SOD group (P < 0.05).n Conclusion: These findings suggested that the reduction in serum SOD activity in elderly patients may be due to weakness of the antioxidant defense of the host, thus resulting in a poor prognosis in those with far-advanced (stage IV) gastric cancer.

Cyclin A expression in superficial squamous cell carcinoma of the esophagus and coexisting infiltrated lymphocyte follicle

Cyclin A is a protein kinase to act a pivotal role in the mitotic phase of the cell cycle. The purpose of the current study was to elucidate the biological significance of immunohistochemical expression of cyclin A in superficial squamous cell carcinoma (SCC) of the esophagus. Immunohistochemical staining of cyclin A was performed for 45 samples of esophageal superficial SCCs. Clinicopathological features were compared between SCCs with and without cyclin A expression. Twenty-five superficial SCCs (55.6%) had positive expression of cyclin A and the other 20 (44.4%) did not. No significant difference regarding clinicopathological characteristics between esophageal SCCs with and without cyclin A expression. Infiltration of lymphocytes with germinal center cells was observed beneath 17 (68.0%) out of 25 superficial SCCs with cyclin A expression and 15 (75.0%) out of 20 superficial SCCs without cyclin A expression. Although 16 (94.1%) out of 17 superficial SCCs with cyclin A expression were associated with cyclin A expression in germinal center cells in infiltrated lymphoid follicles beneath the tumors, only 2 (13.3%) out of 15 superficial SCCs without cyclin A expression coexisted with cyclin A expression in lymphoid follicles beneath the tumors (P<0.0001). Cyclin A expression in the germinal center cells of the lymphoid follicles beneath the superficial SCCs of the esophagus might be an immunological signal toward the proliferation and progression of the tumors.

Clinicopathological significance of pRb2/p130 expression in squamous cell carcinoma of the esophagus

Purpose. The aim of the current study was to find out the significance of the immunohistochemical expression of pRb2/p130, which is a member of the retinoblastoma gene family, in squamous cell carcinoma of the esophagus.Methods. We analyzed immunohistochemically the expression of pRb2/p130 of 107 squamous cell carcinomas (SCCs) of the esophagus and the correlation of pRb2/p130 expression with clinicopathological features was investigated.Results. Expression of pRb2/p130 was observed in 42 SCCs (39.3%). There was a significant correlation of pRb2/p130 expression with the histological type of well-differentiated SCC ( P < 0.0001). The survival rate of patients with esophageal SCCs expressing pRb2/p130 was significantly better than that of patients with tumors without pRb2/p130 expression ( P = 0.016). A multivariate analysis demonstrated that pRb2/p130 expression ( P = 0.026), venous invasion ( P = 0.028), and TNM stage ( P = 0.044) were independent prognostic indicators in patients with esophageal SCCs.Conclusions. Differentiation of esophageal SCC might be partially mediated by the pRb2/p130 gene, and pRb2/p130 expression can additionally be an indicator of the better prognosis of patients with esophageal SCCs.

Increased intestinal permeability correlates with gastrointestinal toxicity among formulations of the fluorouracil analogue tegafur in rats.

Background: S-1 is a new antitumor agent which was developed based on biochemical modulation of fluorouracil. S-1 consists of tegafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), and potassium oxonate (Oxo) in a molar ratio of 1:0.4:1. S-1 has been reported to enhance therapeutic effects and to reduce the gastrointestinal toxicity as compared with 5-fluorouracil. In this study performed in rats, S-1 was used to assess the relationship between gastrointestinal mucosal toxicity and changes in intestinal barrier function. Methods: Fifteen rats were equally divided into three groups: group A (untreated controls), group B (FT and CDHP mixture), and group C (FT and CDHP in combination with Oxo). The animals in groups B and C received equitoxic doses of the drugs in their food for 14 consecutive days. The intestinal permeability was determined on the basis of the urinary recovery of orally administered lactulose and mannitol (L/M). Injury to the small intestines was evaluated by light microscopy. The cell surface expression of CD44 was evaluated immunohistochemically. Results: Recovery of L/M in urine (expressed as a fraction of the dose administered) was 0.15 ± (SE) 0.08, 0.23 ± 0.13, and 0.09 ± 0.04 in groups A, B, and C, respectively. The intestinal permeability in group B was significantly higher than that in group C (p < 0.05). Treatment with FT and CDHP (groups B and C) induced injury to the small intestine and decreased expression of CD44 within the intestinal mucosa, but the extent of damage was reduced by coadministration of Oxo (group C). Conclusion: This experimental study suggested that the gastrointestinal toxicity resulting from administration of anticancer drugs is accompanied by an impaired gut barrier function measurable as an increase in intestinal permeability to L/M.

p34cdc2 expression is an independent indicator for lymph node metastasis in colorectal carcinoma.

PurposeThe significance of p34cdc2 expression in human tumors has not been fully explained. The aim of the current study was to elucidate the clinicopathologic significance of immunohistochemical p34cdc2 expression in carcinoma of the colon and rectum.MethodsThe immunohistochemical expression of p34cdc2 was examined in 90 consecutive colorectal tumor cases, and p34cdc2 expression and the clinicopathologic features of the patients and their tumors were compared.ResultsLymph node metastasis was significantly more frequent in tumors expressing p34cdc2 (47.8%, 11 of 23 tumors) than in tumors not expressing p34cdc2 (22.4%, 15 of 67 tumors; P=0.020). Multivariate analysis demonstrated that tumor depth (P=0.008) and p34cdc2 expression (P=0.022) were independently associated with lymph node metastases of colorectal carcinomas.ConclusionsThe immunohistochemical expression of p34cdc2 is independently associated with lymph node metastasis in colorectal carcinoma.