Pancreatic cancer is currently the major leading cause of cancer-related deaths in the Western countries with an overall 5-year survival rate of less than 3. The key aim of investigation is to identify the cellular population in which some of the earliest molecular events occur, presumably the ultimate target for carcinogenic insult. Advances in pathological classification and genetics have improved our descriptive understanding of this disease. However, important aspects of pancreatic cancer biology remain poorly understood. Factors associated with the increased risk of pancreatic cancer include smoking, chronic pancreatitis, diabetes, prior gastric surgery, and exposure to radiation or chemicals. A number of syndromes have been identified with the increased incidence of pancreatic cancer, including familial atypical multiple-mole melanoma syndrome, hereditary nonpolyposis colorectal cancer, and hereditary pancreatitis, etc. Recently, there have been growing evidences that stem cell biology could provide new insights into the understanding of cancer biology. Three postulates regarding the relationship between stem and tumor cells have been proposed. First, the similarities in the mechanims that regulate self-renewal of normal stem cells and cancer cells. Second, the possibility that tumor cells might arise from normal stem cells and third, the notion that tumors might contain 'cancer stem cells' - rare cells with indefinite proliferative potential which drive the formation and growth of tumors. New insights for the cancer stem cells and their possible markers in pancreatic cancer have been suggested recently. Further observations of molecular and cellular events in the early stage of pancreatic carcinogenesis may have important implications regarding the cellular lineage responsible for pancreatic ductal metaplasia and neoplasia, and provide further support for the presence of stem cell capabilities within mature pancreatic epithelium.
Carcinoma, Pancreatic Ductal/*etiology/genetics/pathology ; Disease Progression ; Humans ; Mutation ; Neoplasm Proteins/genetics ; Neoplastic Syndromes, Hereditary/genetics ; Oncogenes ; Pancreatic Neoplasms/diagnosis/*etiology/genetics ; Risk Factors ; Tumor Markers, Biological

OBJECTIVEThis study was designed to investigate the significance of hTERT mRNA in breast carcinogenesis and to explore the diagnostic efficacy, and to study the effect of tumor suppressor gene p53 on the expression of hTERT mRNA.

METHODSThe expression of hTERT mRNA was examined by in situ hybridization in 12 cases of normal breast tissue nearby cancer, 7 of simple ductal hyperplasia, 20 of atypical hyperplasia, 18 of ductal carcinoma in situ and 25 with invasive ductal carcinoma. The expression of p53 protein were examined by immunohistochemistry in 43 carcinomas.

RESULTShTERT was not detected in normal breast tissue nearby cancer and simple ductal hyperplasia. The positive rate of hTERT mRNA in atypical hyperplasia, ductal carcinoma in situ and invasive ductal carcinoma were 25.0%, 83.3% and 88.0%, respectively. The prevalence and intensity of hTERT mRNA expression were much greater in carcinoma than those in simple or atypical hyperplasia and normal breast tissue nearby cancer (P < 0.05). The expression of hTERT was not correlated with tumor size and lymph node metastasis (P > 0.05). The positive correlation between hTERT mRNA and p53 was found in breast carcinoma (r = 0.5540, P < 0.01).

CONCLUSIONhTERT mRNA expression is closely related to the malignant transformation of breast tissue. Semi-quantitative detection of hTERT mRNA expression in situ is helpful in differentiated diagnosis of carcinoma in situ and atypical hyperplasia. Inactivation of p53 may play a role in the transcriptive activation of hTERT gene in breast carcinoma.

Adult ; Breast ; metabolism ; pathology ; Breast Neoplasms ; genetics ; metabolism ; pathology ; Carcinoma, Ductal, Breast ; metabolism ; pathology ; Carcinoma, Intraductal, Noninfiltrating ; metabolism ; pathology ; Diagnosis, Differential ; Disease Progression ; Humans ; Hyperplasia ; Lymphatic Metastasis ; Middle Aged ; RNA, Messenger ; biosynthesis ; genetics ; Telomerase ; biosynthesis ; genetics ; Tumor Suppressor Protein p53

Breast Neoplasms ; diagnosis ; genetics ; pathology ; Carcinoma, Ductal, Breast ; diagnosis ; genetics ; pathology ; Centromere ; genetics ; Chromosomes, Human, Pair 17 ; genetics ; Early Detection of Cancer ; methods ; Female ; Gene Amplification ; Gene Dosage ; Genes, erbB-2 ; Humans ; Immunohistochemistry ; In Situ Hybridization ; standards ; Receptor, ErbB-2 ; genetics

OBJECTIVETo study the pathologic features, diagnosis, differential diagnosis and molecular characteristics of colloid carcinoma of the pancreas.

METHODSThe clinical findings, morphologic features, immunophenotype and K-ras gene alterations were investigated in 4 cases of pancreatic colloid carcinoma.

RESULTSIn the 4 cases of colloid carcinoma of the pancreas, three tumors were located in the head of the pancreas, one was located in the body and tail. The average age was 56.5 years old. The presenting symptom was abdominal pain in 2 cases, increased level of U-GLU in 1 patient, and an accidental finding presented in 1 patient. Grossly, 3 cases were cystic and solid, with mucin in the cyst; 1 case was solid. Microscopically, the colloid carcinoma was characterized by large pools of extracellular mucin, containing neoplastic cells, which were in the pattern of cuboidal, cribriform or irregular clusters, or formed an incomplete lining separating mucin pools from the stroma. Three cases developed from pre-existing pancreatic ductal adenocarcinoma (IPMN), intestinal-type, and 1 from IPMN, pancreatobiliary-type. Immunohistochemical studies showed that MUC2 was positive in 3 cases, and MUC1 in 1 case. K-ras gene mutation was identified in 2 cases, showing a single-amino-acid substitution in codon 12, as Gly12Asp (GGT > GAT) and Gly12Arg (GGT > CGT).

CONCLUSIONSPancreatic colloid carcinoma is a rare variant of pancreatic ductal adenocarcinoma, which is associated with IPMN and mucinous cystic neoplasms. Positive MUC2 staining and absent MUC1 expression are commonly found, and K-ras gene mutation is occasionally identified in these tumors.

Adenocarcinoma, Mucinous ; genetics ; metabolism ; pathology ; surgery ; Adult ; Aged ; Carcinoma, Pancreatic Ductal ; pathology ; Diagnosis, Differential ; Exons ; Female ; Genes, ras ; Humans ; Male ; Middle Aged ; Mucin-1 ; metabolism ; Mucin-2 ; metabolism ; Mutation ; Pancreatic Neoplasms ; genetics ; metabolism ; pathology ; surgery

Clinicopathological characteristics and prognostic factors of mucinous carcinoma (MC) were compared with invasive ductal carcinoma-not otherwise specified (IDC-NOS). Clinicopathological characteristics and survivals of 104 MC patients were retrospectively reviewed and compared with those of 3,936 IDC-NOS. The median age at diagnosis was 45 yr in MC and 47 yr in IDC-NOS, respectively. The sensitivity of mammography and sonography for pure MC were 76.5% and 94.7%, respectively. MC showed favorable characteristics including less involvement of lymph node, lower stage, more expression of estrogen receptors, less HER-2 overexpression and differentiated grade, and better 10-yr disease-free survival (DFS) and overall survival (OS) (86.1% and 86.3%, respectively) than IDC-NOS (74.7% and 74.9%, respectively). Ten-year DFS of pure and mixed type was 90.2% and 68.8%, respectively. Nodal status and stage were statistically significant factors for survival. MC in Koreans showed similar features to Western populations except for a younger age of onset than in IDC-NOS. Since only pure MC showed better prognosis than IDC-NOS, it is important to differentiate mixed MC from pure MC. Middle-aged Korean women presenting breast symptoms should be examined carefully and evaluated with an appropriate diagnostic work-up because some patients present radiologically benign-like lesions.
Adenocarcinoma, Mucinous/diagnosis/genetics/*pathology ; Adult ; Aged ; Aged, 80 and over ; Breast/pathology ; Breast Neoplasms/classification/diagnosis/genetics/*pathology ; Carcinoma, Ductal/diagnosis/genetics/*pathology ; Disease-Free Survival ; Female ; Genes, erbB-2 ; Humans ; Korea ; Lymphatic Metastasis ; Mammography ; Middle Aged ; Prognosis ; Retrospective Studies ; Sensitivity and Specificity ; Survival Rate ; Young Adult

Carcinoembryonic Antigen ; metabolism ; Carcinoma in Situ ; immunology ; pathology ; virology ; Carcinoma, Ductal, Breast ; immunology ; pathology ; virology ; Cervical Intraepithelial Neoplasia ; immunology ; pathology ; virology ; DNA, Viral ; analysis ; Diagnosis, Differential ; Female ; Human papillomavirus 16 ; genetics ; isolation & purification ; Humans ; Ki-67 Antigen ; metabolism ; Uterine Cervical Dysplasia ; immunology ; pathology ; virology ; Uterine Cervical Neoplasms ; immunology ; pathology ; virology

OBJECTIVETo study the diagnostic criteria, clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma (IMPC) of breast.

METHODSAll cases of breast carcinoma diagnosed during the period from 1989 to 2001 were retrospectively reviewed. One hundred examples with IMPC component, according to the 2003 World Health Organization classification of breast tumors, were identified. The clinicopathologic features and follow-up data of these cases were analyzed.

RESULTSAmongst the 100 cases of IMPC studied, 69% (69/100) had evidence of lymphovascular invasion. The incidence of regional lymph node metastasis was 84.8% (84/99). Follow-up information was available in 98 patients (mean of follow-up duration = 60.1 months). Eleven patients (11.2%) had local recurrence within a mean of 26.4 months after the operation, while 38 patients (38.8%) had distant metastases within a mean of 36.0 months. Thirty-six patients (36.7%) died of the disease. The overall 5-year survival rate was 59% and the 10-year survival rate was 48%. Univariate and multivariate analysis showed that the prognosis of patients was adversely affected by the presence of lymphovascular invasion and family history of breast cancer. On the other hand, tamoxifen therapy and adjuvant chemotherapy improved survival.

CONCLUSIONSBreast carcinoma with IMPC component is associated with poor prognosis, despites the relative proportion of this architectural pattern. The overall prognosis is related to the presence of lymphovascular invasion and family history of breast cancer. Hormonal therapy and individualized chemotherapy can improve the survival rate.

Adult ; Aged ; Antineoplastic Agents, Hormonal ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Neoplasms ; secondary ; Breast Neoplasms ; diagnosis ; genetics ; pathology ; therapy ; Carcinoma, Ductal, Breast ; diagnosis ; genetics ; pathology ; therapy ; Carcinoma, Papillary ; diagnosis ; genetics ; pathology ; therapy ; Chemotherapy, Adjuvant ; Cyclophosphamide ; therapeutic use ; Female ; Fluorouracil ; therapeutic use ; Follow-Up Studies ; Genetic Predisposition to Disease ; Humans ; Liver Neoplasms ; secondary ; Lymphatic Metastasis ; Mastectomy ; methods ; Methotrexate ; therapeutic use ; Middle Aged ; Neoplasm Recurrence, Local ; Proportional Hazards Models ; Radiotherapy, Adjuvant ; Retrospective Studies ; Survival Rate ; Tamoxifen ; therapeutic use