Expression of FAK and PTEN in Bronchioloalveolar Carcinoma and Lung Adenocarcinoma

Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung adenocarcinoma but has a distinct clinical presentation, tumor biology, response to therapy, and prognosis compared with other subtypes of lung adenocarcinoma. This study was designed to investigate the clinicopathological differences between BAC and adenocarcinoma and the expression of focal adhesion kinase (FAK) and phosphatase and tensin homologue (PTEN) and their clinical significance in BAC and adenocarcinoma. A retrospective analysis was performed on 77 patients with BAC and 172 patients with pure adenocarcinoma seen during the period from January 1998 to December 2000. All patients underwent lobectomy or pneumonectomy and systematic lymph node dissection. Paraffin-embedded tissue blocks from these patients were obtained and expressions of PTEN and FAK were evaluated by using immunohistochemical staining. Clinicopathological characteristics and survival outcome were reviewed and compared between patients with BAC and adenocarcinoma. Lymph node status, clinical symptoms, CT appearance and expression of FAK were different between BAC and adenocarcinoma. The overall survival of BAC was better than that of adenocarcinoma. In patients with FAK(−), the overall survival was not different between BAC and adenocarcinoma. In patients with adenocarcinoma, the overall survival was better for FAK(−) compared with FAK(+). Expression of PTEN had a prognostic significance in patients with BAC and adenocarcinoma. BAC and adenocarcinoma have different clinicopathological presentations. Expression of FAK has some effect on such differences and affects survival of lung adenocarcinoma. Expression of PTEN can predict outcome of resected lung adenocarcinoma and BAC.     

Adenocarcinoma arising from heterotopic gastric mucosa in the cervical esophagus and upper thoracic esophagus: two case reports and literature review

Primary adenocarcinoma arising from heterotopic gastric mucosa (HGM) is rare and the clinicopathological characteristics are not well known. We present two cases of esophageal adenocarcinoma arising from HGM with a review of a case series. Case 1 was a 78-year-old woman who underwent a periodic medical examination without complaining of any symptoms. Preoperative evaluation suggested esophageal adenocarcinoma arising from the HGM. The patient was treated with endoscopic submucosal dissection. Definitive pathological diagnosis confirmed adenocarcinoma arising from the HGM. Case 2 was a 70-year-old man who underwent a medical examination after complaining of dysphagia. Preoperative diagnosis suggested esophageal adenocarcinoma; however, its origin was unclear. The patient was treated with surgical resection. Definitive pathological diagnosis revealed adenocarcinoma arising from the HGM. In this article, the authors report the clinicopathological features of esophageal adenocarcinoma arising from HGM that were collected from a literature review and our cases.     

Relation of Histopathological Features to Prognosis of Gallbladder Cancer

Sixty-four cases of gallbladder cancer surgically removed were histologically divided into three groups, that is, papillary adenocarcinoma, tubular adenocarcinoma, and undifferentiated carcinoma, and were compared clinicopathologically. The results are as follows. Papillary adenocarcinoma showed little gender preponderance and had a low association with gallstones. Underlying chronic cholecystitis or epithelial metaplasia was infrequent. Most cases were in the early stage, with favorable prognosis. Tubular adenocarcinoma, seen predominantly in females with gallstones, showed a downward invasive growth with unfavorable prognosis. Chronic cholecystitis and epithelial metaplasia were frequent. Undifferentiated carcinomas were common in females with gallstones, and their prognosis was the worst of the three. It was concluded that papillary adenocarcinoma differed from both tubular adenocarcinoma and undifferentiated carcinoma in biological behavior. The former appears to arise mainly from the native gallbladder epithelium, whereas the latter two types frequently arise from metaplastic epithelium.     

Reduced expression of p53 and cyclin A in intraductal mucin-hypersecreting neoplasm of the pancreas compared with usual pancreatic ductal adenocarcinoma

OBJECTIVE: Intraductal mucin-hypersecreting neoplasm (IMHN) of the pancreas, a slow-growing malignancy with a favorable prognosis, is distinctly categorized from the high-grade malignancy of the more common ductal adenocarcinoma. The aim of the present study was to clarify the molecular differences underlying the biological differences between IMHN and ductal adenocarcinoma of the pancreas. METHODS: The expression of p53 and cyclin A in IMHN was compared with that in ductal adenocarcinoma of the pancreas immunohistochemically. RESULTS: In IMHN, the incidence of p53 and cyclin A ascertained by positive nuclear staining was significantly lower than that in ductal adenocarcinoma. Furthermore, in ductal adenocarcinoma, p53 and cyclin A are topographically coexpressed. CONCLUSIONS: These results suggest that the overexpression of p53 and cyclin A plays a role in the tumorigenesis of pancreatic ductal adenocarcinoma, and sparse expression of both antigens in IMHN may partly contribute to its low-grade malignant characteristics.     

Incidence and Survival of Mucinous Adenocarcinoma of the Colorectum: A Population-Based Study From an Asian Country

PURPOSE: Previous studies have shown conflicting results on the prognosis of mucinous adenocarcinoma of the colorectum. This could be because of heavy bias on patient selection. Furthermore, little data are available from Asian populations. This study was designed to examine incident and prognostic characteristics of mucinous adenocarcinoma of the colorectum based on data obtained from a population-based, Asian, cancer registry. METHODS: A total of 627 of 15,762 were mucinous adenocarcinoma cases from invasive colorectal cancer patients registered in the Singapore Registry from 1968 to 1997. Age-standardized incidence rate was used to describe the incident pattern of mucinous adenocarcinoma of colon and rectum during a period of time. Survival of patients with mucinous adenocarcinoma or ordinary adenocarcinoma was compared using relative survival and proportional hazards model. RESULTS: Age-standardized incidence rate of mucinous adenocarcinoma of the colon and rectum were almost unchanged in males, rising slightly in females during the study periods from 1968 to 1972 to 1993 to 1997. The proportion of mucinous adenocarcinoma cases was similar among genders and calendar-year periods but was higher in younger age groups, Malays and Indians, in advanced stages of the disease, and proximal colon. Five-year relative survival rate of patients with mucinous adenocarcinoma were similar in the colon but were lower in the rectum. CONCLUSIONS: Colorectal mucinous adenocarcinoma as a different etiologic entity from other histologic types of colorectal cancer was suggested. Possibly greater aggressiveness of mucinous adenocarcinoma occurring in the rectum requires confirmation but suggests that mucin is important in the pathogenesis of mucinous adenocarcinoma.     

Familial aggregation of Barrett's oesophagus,oesophageal adenocarcinoma,and oesophagogastric junctional adenocarcinoma in Caucasian adults

BACKGROUND: Although familial clusters of Barrett's oesophagus and oesophageal adenocarcinoma have been reported, a familial predisposition to these diseases has not been systematically investigated. AIMS: To determine whether Barrett's oesophagus and oesophageal (or oesophagogastric junctional) adenocarcinoma aggregate in families. PATIENTS AND METHODS: A structured questionnaire eliciting details on reflux symptoms, exposure history, and family history was given to Caucasian case (n=58) subjects with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma, and to Caucasian control (n=106) subjects with symptomatic gastro-oesophageal reflux disease without Barrett's oesophagus. Reported diagnoses of family members were confirmed by review of medical records. RESULTS: The presence of a positive family history (that is, first or second degree relative with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma) was significantly higher among case subjects compared with controls (24% v 5%; p<0.005). Case subjects were more likely to be older (p<0.001) and male (74% v 43% male; p<0.0005) compared with control subjects. In a multivariate logistic regression analysis, family history was independently associated with the presence of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma (odds ratio 12.23, 95% confidence interval 3.34-44.76) after adjusting for age, sex, and the presence of obesity 10 or more years prior to study enrollment. CONCLUSIONS: Individuals with Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma are more likely to have a positive family history of Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma than individuals without Barrett's oesophagus, oesophageal adenocarcinoma, or oesophagogastric junctional adenocarcinoma. A positive family history should be considered when making decisions about screening endoscopy in patients with symptoms of gastro-oesophageal reflux.     

胰腺癌组织表皮生长因子mRNA表达的意义

目的探讨ＥＧＦｍＲＮＡ的表达与胰腺癌发生、发展及预后的关系．方法应用Ｎｏｒｔｈｅｒｎｂｌｏｔ杂交方法，检测胰腺癌２７例和正常胰组织７例中ＥＧＦｍＲＮＡ表达．结果正常胰腺组织７例未检测到ＥＧＦｍＲＮＡ表达，胰腺癌２７例ＥＧＦｍＲＮＡ阳性表达率６６７％（１８例），经卡方检验发现，ＥＧＦｍＲＮＡ表达与胰腺癌病理分级、临床分期及伴随局部淋巴结转移呈显著相关（Ｐ＜００５）．结论ＥＧＦｍＲＮＡ表达与胰腺癌发生有关，胰腺癌ＥＧＦｍＲＮＡ表达可作为胰腺癌预后的参考指标     

Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan

Introduction: A dramatic increase in incidence of adenocarcinoma of the esophagogastric junction (EGJ) over the past two decades has been reported in the West. However, epidemiological data from Asian countries have not shown a similar trend. The aim of this study was to determine the incidence of adenocarcinoma of the EGJ in a cohort of consecutive patients operated on for gastric adenocarcinoma at a major cancer referral center in Japan. Method: We reviewed pathological reports of all patients who underwent surgery for advanced gastric adenocarcinoma between 1962 and 2005 at the National Cancer Centre Hospital in Tokyo. Adenocarcinoma of the EGJ was defined from images recorded for each patient, in accordance with the classification of Siewert and Stein. The proportion of adenocarcinoma at the EGJ among operated gastric adenocarcinoma patients was compiled at five‐year intervals and serial comparison made. Results: A total of 6953 patients with advanced gastric adenocarcinoma were operated on; adenocarcinoma of EGJ was found in 520 patients. The overall proportion of adenocarcinoma of the EGJ increased from 2.3% (1962–1965) to 10.0% (2001–2005). The proportion of Siewert Type II rose from 28.5% (1962–1965) to 57.3% (2001–2005), while that of Type I remained at around 1%. Conclusion: An increasing trend of adenocarcinoma of EGJ is observed in this study of patients operated on for gastric adenocarcinoma from 1962 to 2005 in a large tertiary referral center in Japan.     

Notch1蛋白在人肺腺癌组织中的表达及意义

目的 研究Notch1蛋白在人肺腺癌组织中的表达及意义,探讨Notch1受体在人肺腺癌发生中的作用.方法 前期研究初步筛选出Notch1蛋白在肺腺癌组织中有强表达,本研究收集我院及新华医院2009年1月至2010年5月胸外科肺癌手术并经术后病理切片明确为肺腺癌的标本以及正常肺组织标本,以实时荧光定量PCR及Wester...     

Clinical significance of cathepsin E in pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma

BACKGROUND: It has been reported that cathepsin E (CTSE) is a non-secretory and intracellular aspartic proteinase found in the superficial epithelial cells of the stomach and that it is also expressed in pancreatic ductal adenocarcinoma. We evaluated the diagnostic value of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma compared with that of CA19-9, carcinoembryonic antigen (CEA) and K-ras mutations. METHODS: One hundred and one patients (25 with pancreatic ductal adenocarcinoma and 76 with chronic pancreatitis) were examined for the diagnostic significance of CTSE in the pancreatic juice in the diagnosis of pancreatic ductal adenocarcinoma. Forty of 101 patients (15 with pancreatic ductal adenocarcinoma and 25 with chronic pancreatitis) were examined to compare the diagnostic value of various tumor markers in the pancreatic juice, namely CA19-9, CEA, K-ras mutations and CTSE. RESULTS: The detection frequency of CTSE was significantly higher in patients with pancreatic ductal adenocarcinoma (64.0%) than in patients with chronic pancreatitis (7.9%; chi2 = 34.76; P < 0.0001). The sensitivity, specificity and diagnostic accuracy of CTSE in the pancreatic juice for pancreatic ductal adenocarcinoma was 66.7, 92.0 and 82.5%, respectively. These values were more efficient in comparison with those of CA19-9, CEA and K-ras mutations. The main cause of the detection failure of CTSE in pancreatic ductal adenocarcinoma was obstruction of the main pancreatic duct. Sensitivity was 85.7% in patients without obstruction of the main pancreatic duct. CONCLUSIONS: Cathepsin E in the pancreatic juice is a novel marker for a definitive diagnosis of pancreatic ductal adenocarcinoma.     

Association of the HLA-DRB1 gene locus with gastric adenocarcinoma in Japan

BACKGROUND AND AIM: Helicobacter pylori infection is associated with gastric adenocarcinoma, however, the odds ratio is relatively low. The aim of the present study was to investigate host genetic factors that increase the risk of gastric adenocarcinoma among H. pylori-infected individuals. METHODS: A total of 70 patients with early gastric adenocarcinoma and 121 unrelated healthy controls were examined for H. pylori infection and HLA-DRB1 genotyping. The frequencies of HLA-DRB1 alleles were compared among groups. RESULTS: The allele frequency of DRB1*04051 was significantly higher in patients with gastric adenocarcinoma (17.9%) than in controls (7.9%) (P(correct) = 0.045). The odds ratio of gastric adenocarcinoma associated with the presence of the HLA-DRB1*04051 allele compared with its absence was 2.55 (95% confidence limits, 1.35-4.83). This genetic risk was not associated with H. pylori infection. There was no significant difference in the HLA-DRB1 allele frequency between H. pylori-positive and H. pylori-negative controls. The frequency of genotypes that possessed the DRB1*04051 allele in gastric adenocarcinoma patients (34.3%) was significantly higher than that in H. pylori-negative controls (11.9%) (p = 0.0089) and H. pylori-positive controls (15.2%) (p = 0.0066). CONCLUSION: These findings suggest that immunogenetic factors for susceptibility to gastric adenocarcinoma are present in the host, the HLA-DRB1*04051 allele is a host genetic risk factor for gastric adenocarcinoma, and that this genetic risk is independent of H. pylori infection.     

CEACAM5在肺腺癌中的表达及临床意义

目的 通过检测癌胚抗原相关细胞黏附分子5(CEACAM5)在肺腺癌中的表达,探究其临床意义及预后.方法 回顾性分析2016年8月-2017年8月在本院确诊为肺腺癌的患者51例,取肺腺癌患者病变肺部组织作为实验组;从中选取42例取癌旁组织作为对照组.采用免疫组化SP法检测肺部肺腺癌组织和癌旁组织CEACAM5的表达,并利...     

Trop-2在肺腺癌组织和细胞系中的表达及临床病理分析

目的研究滋养层细胞表面抗原-2（Trop-2）在肺腺癌组织和细胞系中的表达及其临床病理意义。方法RT—PCR检测9例肺腺癌组织和20例癌旁组织中Trop-2mRNA的表达,免疫荧光检测人肺腺癌细胞系中Trop-2蛋白表达。分析Trop-2的表达同临床病理特征之间的相关性。结果在不同人肺腺癌细胞系中Trop-2表达的阳性率不同,于正常人支气管上皮细胞系中无表达。Trop-2mRNA在肺腺癌细胞系中有表达,Trop-2蛋白表达主要在肺腺癌细胞膜上;Trop-2在人肺腺癌组织中的阳性率显著高于癌旁组织;阳性表达程度随癌组织分化程度的降低而增高（P〈0．05）;Trop-2的表达同患者年龄、性别不相关（P〉0．05）。结论Trop-2在肺癌组织和肺癌细胞系中高表达,可作为检测人肺腺癌恶性程度的标记物。     

Tumorigenicity,invasion, and metastasis of human gastric cancer in nude mice

Summary Tumors derived from 105 patients with gastric cancer were subcutaneously heterotransplanted into nude mice in order to study their tumorigenicity and malignant behavior. Of the 105 gastric cancers, 45 were successfully transplanted (a 42.9% tumorigenesis rate). The tumorigenesis rate of Borrmann type 1 and 2 cancers (77.8%) was significantly higher than that of type 3 and 4 cancers (34.6%). Also, the tumorigenesis rate of differentiated carcinoma (57.1 %) was significantly higher than that of undifferentiated carcinoma (30.9%). Spontaneous metastases from the subcutaneous tumors were observed in 5 of the 37 established tumor lines (13.5%), and macroscopic pulmonary metastases were common with one tumor line (SCK-29). Although most of the subcutaneous gastric cancers showed local expansion without distant metastasis, the same tumor cells implanted into the peritoneal cavity exhibited invasive growth and/or metastasis. Thus, the expression of a metastatic pheno-type by human gastric cancer was influenced by the host microenvironment. The SCK-29 tumor line with its high metastatic potential may be useful for studies on the mechanism of blood-borne metastasis.Abbreviations pap papillary adenocarcinoma - tub₁ well-differentiated adenocarcinoma - tub₂ moderately differentiated adenocarcinoma - por poorly differentiated adenocarcinoma - sig signet-ring cell adenocarcinoma - muc mucinus adenocarcinoma - giant giant cell adenocarcinoma - ud undifferentiated adenocarcinoma - ade ascitic adenocarcinoma This study was supported in part by a grant-in aid for cancer research (B.no. 63480309) from the Ministry of Education, Science and Culture, Japan     

Anorectal Mucinous Adenocarcinoma Associated with Latent Perianal Paget''s Disease

We report a case (63-yr-old man) of anorectal mucinous adenocarcinoma associated with perianal Paget's disease, found incidentally by pathologic examinations of the resected specimen. Paget's disease resided just distal to the anorectal adenocarcinoma. The area of Paget's disease was rather small. The epidermis containing Paget's cells was continuous with the anorectal adenocarcinoma, as if adenocarcinoma cells invaded directly into the epidermis. The Paget's cells were positive for neutral and acid mucus. Ultrastructurally, Paget's cells contained secretory granules, microvilli, and a few tight junctions, but lacked tonofilaments. The mucinous adenocarcinoma cells also showed histochemical and ultrastructural features that were similar to those of Paget's cells. These findings strongly suggest that the Paget's cells were derived from direct spread from the anorectal adenocarcinoma, in this case. Clinicians and pathologists should carefully examine the perianal epidermis in anorectal carcinoma, even if there are no clinical findings of perianal Paget's disease. The English literature is also reviewed briefly.     

Association of esophageal adenocarcinoma with other subsequent primary cancers

PURPOSE: Esophageal adenocarcinoma shares risk factors such as obesity and smoking with other common cancers. The association of esophageal adenocarcinoma with other primary cancers has not been systematically evaluated. The authors used the Surveillance, Epidemiology and End-Results database of the National Cancer Institute to explore the association of esophageal adenocarcinoma with other primary cancers. PATIENTS AND METHODS: All adult patients with esophageal cancers, both adenocarcinoma and squamous cell carcinoma diagnosed between 1973 and 2001, were identified from the Surveillance, Epidemiology, and End-Results database, and standardized incidence rates were calculated for all subsequent primary cancers in these patients. The analysis was reversed to estimate the standardized incidence rate for subsequent primary esophageal cancer after a first primary cancer. RESULTS: In comparison with a standard population, patients with esophageal adenocarcinoma were at higher risk for the development of another subsequent cancer, specifically, cancers of the oral cavity and pharynx, lung and bronchus, and kidney and renal pelvis, and adenocarcinoma of the colon/rectum and pancreas. With squamous cell esophageal cancer, there was an association with tobacco-related cancers such as those of the oral cavity and pharynx, the lung and bronchus, and the breast. There was either no association or even a negative association of esophageal adenocarcinoma with other obesity-related cancers such as breast, uterine, and prostate cancers. CONCLUSIONS: Patients with esophageal adenocarcinoma and squamous cell carcinoma are at increased risk for the development of specific second primary cancers that share smoking as a common risk factor. Esophageal adenocarcinoma does not have a strong association with obesity-related cancers with respect to the relative risk for the development of subsequent primary cancers.     

Helicobacter pylori-associated antibodies in patients with duodenal ulcer, gastric and oesophageal adenocarcinoma

OBJECTIVE: To associate Helicobacter pylori-associated antibodies with clinical disease in groups of patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. DESIGN: Prospective observational sero-epidemiology study. Identification of consecutive in-patients with duodenal ulcer, gastric adenocarcinoma, oesophageal adenocarcinoma and normal mucosa. Analyses of sera for antibodies to whole H. pylori, Cag A and Vac A antigens using ELISA and Western blot. Statistical analyses. SETTING: Walsgrave Hospital, Coventry, a district general hospital that serves a population of 350,000. PARTICIPANTS: Consecutive in-patients with an endoscopic diagnosis of duodenal ulcer (n = 31), gastric adenocarcinoma (n = 31), oesophageal adenocarcinoma (n = 40) and normal mucosa (n = 46). MAIN OUTCOME MEASURES: A profile of antibodies was constructed for each patient group and between-group comparisons were made. A logistic regression model determined the H. pylori-associated antibody that could best predict a patient's diagnosis. A discriminatory power for each antibody was calculated. RESULTS: Whole H. pylori, Cag A and Vac A antibodies are found more commonly in duodenal ulcer patients when compared to oesophageal adenocarcinoma (P < 0.003) and normal mucosa patients (P < 0.015). Similarly, gastric adenocarcinoma patients have antibodies to whole H. pylori, Cag A and Vac A more frequently than oesophageal adenocarcinoma (P< 0.002) and normal mucosa patients (P < 0.006). Vac A antibodies discriminate between duodenal ulcer/gastric adenocarcinoma and oesophageal adenocarcinoma/normal mucosa patients (odds ratio 5.56, log likelihood -90.06, P < 0.001) more effectively than Cag A antibodies (odds ratio 4.17, log likelihood -91.88, P < 0.001). CONCLUSIONS: Similar profiles of H. pylori-associated antibodies are seen in patients with duodenal ulcer and gastric adenocarcinoma, confirming that virulent H. pylori are involved in the pathogenesis of both diseases. Antibodies to Vac A could be used to identify patients at increased risk of developing H. pylori-associated disease.