epidermal-growth-factor and Adenocarcinoma--Mucinous

This study aimed to investigate serum levels of epidermal growth factor (EGF), transforming growth factor α (TGF-α), and c-erbB2 in patients with ovarian cancer.. In this retrospective cohort study, the study and control groups were composed of 43 women with a prediagnosis of ovarian cancer and 43 healthy women, respectively. Blood samples from all women were obtained and studied by enzyme-linked immunosorbent assay kits for EGF, TGF-α, and c-erbB2. After surgery of the study group, ovarian cancer was confirmed and compared with control group. Stage, grade, and histological types were defined after histopathologic examination, and subgroups were constructed and compared.. Serum EGF, TGF-α, and c-erbB2 levels were significantly increased in study group compared with those in the control group (P < 0.001). There were no differences in serum levels of EGF, TGF-α, and c-erbB2 among all stages, grades, and histological types of ovarian cancer. If 47.90 pg/mL was selected as the cutoff value, EGF has an 80% sensitivity and a 65% specificity for detecting ovarian cancer. The cutoff value of 41,095.00 pg/mL for TGF-α has a 90% sensitivity and a 72% specificity for detecting ovarian cancer. The c-erbB2 level of 4.63 pg/mL as the cutoff value has an 83% sensitivity and a 76% specificity for predicting ovarian cancer.. Serum levels of EGF, TGF-α, and c-erbB2 may be used for diagnosing ovarian cancer.

Topics: Adenocarcinoma, Clear Cell; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Case-Control Studies; Cystadenocarcinoma, Serous; Endometrial Neoplasms; Enzyme-Linked Immunosorbent Assay; Epidermal Growth Factor; Female; Humans; Middle Aged; Neoplasm Grading; Neoplasm Staging; Ovarian Neoplasms; Prognosis; Receptor, ErbB-2; Retrospective Studies; ROC Curve; Transforming Growth Factor alpha

Epiregulin (Ep) was found to be produced in non-cancer ovarian cells in response to gonadotropin stimulation as well in ovarian cancer cells in an autonomous manner. However, there were no systematic follow-up studies of Ep expression in the development of different stages of ovarian cancer. Using specific antibodies to Ep and the indirect immunocytochemistry methods, we found that in normal ovary the staining for Ep was mainly confined to the epithelial cells, while the stromal cells were only occasionally and moderately stained. In contrast in benign serous and mucinous tumors most of the tumor cells showed a clear staining in the cytoplasm. In borderline serous and mucinous tumors the staining was much more intensive, and appear occasionally in aggregated form. In serous, mucinous and endometrioid carcinomas labeling remain high, with more frequent aggregated form. It is suggested that follow-up of the expression of Ep can serve as a reliable early indication of the development of ovarian cancer. Moreover, the cytoplasmic aggregation of Ep may suggest a specific mechanism of the release of this growth factor to the extracellular space in order to exert its autocrine and paracrine effect on the family of the EGF receptors.

Topics: Adenocarcinoma, Mucinous; Biomarkers, Tumor; Epidermal Growth Factor; Epiregulin; Female; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Staging; Ovarian Neoplasms; Ovary

Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.

Topics: Adenocarcinoma, Mucinous; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Medullary; Chi-Square Distribution; Epidermal Growth Factor; Estrogen Receptor alpha; Female; Humans; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Keratins; Multidrug Resistance-Associated Proteins; Neoplasm Staging; Patient Selection; Phosphorylation; Up-Regulation; Vault Ribonucleoprotein Particles

Human Cripto-1, a membrane-bound protein, plays an important role during early embryogenesis and has oncogenic properties, including cell transformation and enhancement of invasion. Cripto-1 is up-regulated in various malignant tissues and premalignant lesions. However, Cripto-1 expression in intraductal papillary mucinous neoplasms (IPMNs) has yet to be reported. This study aimed to investigate Cripto-1 expression in IPMNs and evaluate the expression patterns according to the histological grade or phenotypic subclassification. Cripto-1 expression was evaluated by immunohistochemistry using 37 IPMN tissue samples and real-time RT-PCR analysis of seven frozen samples. Cripto-1 was up-regulated in 59.5% of IPMNs. Cripto-1 was positively stained in 3 of 4 (75%) adenomas, 12 of 19 (63.2%) borderline neoplasms, 5 of 11 (45.5%) non-invasive carcinomas and 2 of 3 (66.7%) invasive carcinomas. There was no correlation between Cripto-1 overexpression and the histological grade (P>0.05). Cripto-1 expression was significantly increased in pancreatobiliary- (4/5, 80%) and gastric-type (13/19, 68.4.2%) IPMNs compared with those of the intestinal type (2/10, 20%; P<0.01). Cripto-1 mRNA expression was higher in gastric- and pancreatobiliary-type IPMNs than in intestinal ones, supporting the immunohistochemical results. It is concluded that Cripto-1 overexpression is involved in the tumorigenesis of gastric- and pancreatobiliary-type IPMNs.

Topics: Adenocarcinoma, Mucinous; Adenocarcinoma, Papillary; Adult; Aged; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Epidermal Growth Factor; Female; Gene Expression; GPI-Linked Proteins; Humans; Immunohistochemistry; Intercellular Signaling Peptides and Proteins; Male; Membrane Glycoproteins; Middle Aged; Neoplasm Proteins; Pancreatic Neoplasms; Reverse Transcriptase Polymerase Chain Reaction

Growth factors are important mediators of proliferation. Deregulation in growth factor mechanisms as well as in its receptors will contribute to cancer development. One of the most important is the epidermal growth factor (EGF), which is encoded by EGF gene. A functional polymorphism at position 61 (A/G) is associated with increased expression of EGF. Thus, we proposed to assess genotype frequencies in a case-control study and appraise their association to breast cancer risk. Using the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) we analyzed DNA from 883 women (500 controls and 383 breast cancer patients). Our results suggested that carriers of G homozygous genotype had a lower risk for developing breast cancer (odds ratio = 0.68; 95% confidence intervals, 0.46-1.01). Further, we showed that the waiting time for onset of breast cancer in G homozygous patients for EGF genotypes (55 years) was significantly lower in comparison to A-allele carriers (59 years) (log-rank test: p = 0.038). EGF is produced in mammary tissue and acts in the mammalian development. A lower risk for breast cancer in GG carriers might be explained through EGF receptor internalization promoted by EGF.

Topics: Adenocarcinoma, Mucinous; Adult; Age of Onset; Breast Neoplasms; Carcinoma, Ductal, Breast; Carcinoma, Lobular; Carcinoma, Papillary; Case-Control Studies; Epidermal Growth Factor; ErbB Receptors; Female; Genotype; Humans; Middle Aged; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Prognosis

Pancreatic cystic neoplasms and ductal adenocarcinoma manifest diverse clinical features and prognoses, which might be related to cellular distribution of ezrin modulated through various trophic molecules.. Laboratory investigation and retrospective analysis.. Medical school-affiliated university hospital.. Patients with solid pseudopapillary tumor (SPT) (n = 12), mucinous cystic neoplasm (MCN) (n = 18), intraductal papillary mucinous tumor (IPMT) (n = 18), and ductal adenocarcinoma (PA) (n = 73) of the pancreas were studied. Expression of epidermal growth factor (EGF) and its receptor (EGFR) and ezrin were determined using immunohistochemistry. Epidermal growth factor receptor and ezrin expression in sodium butyrate (SB)-treated PA cell line PANC-1 was determined using immunocytochemistry. Messenger RNA expression of ezrin in the PANC-1 cell line treated with SB was determined using reverse transcriptase-polymerase chain reaction. Multivariate analysis of survival of patients with PA was performed.. None of 12 SPTs displayed synchronous expression of EGF and EGFR, while all 3 malignant SPTs displayed membranous ezrin expression. One of 18 MCNs displayed synchronous expression of EGF and EGFR, while 4 of 6 borderline malignant and 8 of 8 malignant MCNs displayed membranous ezrin expression. Two of 4 borderline malignant and 11 of 11 malignant IPMTs displayed synchronous expression of EGF and EGFR, and all borderline malignant and malignant IPMTs displayed membranous ezrin expression. Less differentiated PA displayed EGF, EGFR, and membranous ezrin expression more frequently compared with more differentiated PA. Epidermal growth factor receptor expression of PANC-1 cells decreased in an SB dose dependent manner, in which PANC-1 cells became more differentiated and membranous ezrin expression of PANC-1 cells decreased correspondingly. Messenger RNA expression of ezrin in PANC-1 cells also decreased in an SB dose dependent manner. Patients with PA with membranous ezrin expression had a poorer prognosis compared with those without (P = .02).. Membranous translocation of ezrin might play a role during malignant transformation of SPT, MCN, IPMT, and PA, which are either dependent on (IPMT and PA) or independent of (SPT and MCN) the EGF-EGFR pathway. Membranous ezrin expression represents a prognostic factor for PA.

Topics: Adenocarcinoma, Mucinous; Adolescent; Adult; Aged; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Cytoskeletal Proteins; Disease Progression; Epidermal Growth Factor; ErbB Receptors; Female; Humans; Immunoenzyme Techniques; Male; Middle Aged; Multivariate Analysis; Pancreatic Neoplasms; Phosphoproteins; Prognosis; Proportional Hazards Models; Retrospective Studies; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Survival Rate

Immunohistochemical staining for EGF, EGFR, c-erbB-2, p53, K-ras and PCNA was performed on the formalin-fixed, paraffin embedded sections of resected gastric carcinomas. A relatively high positive rate was observed for EGFR and c-erbB-2 in the well-differentiated adenocarcinomas and p53 in the poorly-differentiated adenocarcinomas. The positive rate of these factor was higher in the advanced cases than in the early cases, and also in the deep invasive area than the superficial area. According to the PCNA staining, a relatively high positive rate was observed in the well-differentiated adenocarcinomas compared with the early cases of poorly-differentiated adenocarcinomas, but the positive rate was markedly higher in the advanced cases of the latter. Typical signet-ring cell carcinomas showed the lowest positivity rate compared with the other histological types of gastric carcinomas.

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Epidermal Growth Factor; ErbB Receptors; Genes, p53; Genes, ras; Humans; Immunohistochemistry; Nuclear Proteins; Proliferating Cell Nuclear Antigen; Stomach Neoplasms

Topics: Adenocarcinoma; Adenocarcinoma, Mucinous; Cell Division; Cell Line; Cell Survival; Drug Screening Assays, Antitumor; Drug Synergism; Epidermal Growth Factor; ErbB Receptors; Fluorouracil; Humans; Stomach Neoplasms; Tumor Cells, Cultured