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Met proto-oncogene and insulin-like growth factor binding protein 3 overexpression correlates with metastatic ability in well-differentiated pancreatic endocrine neoplasms.

Pancreatic endocrine neoplasms are neoplastic proliferations of islet cells or islet cell precursors and are capable of secreting a variety of synthetic products, including insulin, glucagon, gastrin, and vasoactive intestinal peptide. The biological behavior of pancreatic endocrine neoplasms is often unpredictable, and there are few reliable histopathologic criteria reliably correlating with metastatic ability. We have used the Affymetrix U133 GeneChip set (HG_U133 A and B; Affymetrix; Santa Clara, CA) representing approximately 33,000 characterized transcripts to examine global gene expression profiles from well-differentiated nonmetastatic (n=5) and metastatic (n=7) pancreatic endocrine neoplasms to determine molecular markers that predict disease progression. Microarray hybridization data were normalized using the GeneLogic GeneExpress Software System to identify differentially up- and down-regulated genes in metastatic versus nonmetastatic pancreatic endocrine neoplasms. Using a 3-fold change in gene expression as a threshold, we have identified 65 overexpressed and 57 underexpressed genes in metastatic pancreatic endocrine neoplasms as compared with nonmetastatic pancreatic endocrine neoplasms. Several classes of genes, including growth factors and growth factor-related molecules (IGFBP1, IGFBP3, and MET), developmental factors (TBX3 and MEIS2), cytoskeletal factors (beta 1 tubulin and ACTN2), cholesterol homeostasis mediators (LRP5, SLC27A2, and RXRG), intracellular signaling pathway mediators (DYRK1A, PKIB, and AK2), methyltransferases (MGMT and GAMT), and DNA repair and regulatory molecules (CHEK1 and ZNF198), were identified as differentially over- or underexpressed via this method. Immunohistochemical validation of microarray data were performed for two overexpressed genes, namely, the met proto-oncogene (MET) and insulin-like growth factor binding protein 3 (IGFBP3) with tissue microarrays of nonmetastatic (n=24) and metastatic (n=15) pancreatic endocrine neoplasms. Increased expression of IGFBP3 was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (12 of 15, 80% versus 10 of 24, 42%), as well as in lymph node (6 of 7, 86%) and liver (9 of 9, 100%) metastases. Similarly, overexpression of MET was confirmed in metastatic versus nonmetastatic pancreatic endocrine neoplasms (5 of 15, 33% versus 4 of 24, 17%), as well as in lymph node metastases (4 of 7, 57%) and liver metastases (5 of 9, 56%). The majority of genes that demonstrated altered expression has not been previously identified as differentially expressed in metastatic pancreatic endocrine neoplasm lesions and may therefore represent newly identified molecules in the progression of these lesions.

Aged↗

Spontaneous skin neoplasms in aged Sprague-Dawley rats.

A total of 93 tumors of the epidermis, its appendages, and dermis were observed in 1,433 (717 males, 716 females) rats employed in oncogenicity studies over a 2-yr period. Mammary gland neoplasms will be reported separately. Fifty-seven (61.3%) were epithelial with 49 in males and 8 in females. Keratoacanthoma was the most frequent epithelial neoplasm in males (22) followed by squamous cell carcinoma (11) and papilloma (5). Sebaceous gland neoplasms seen in males (5) included both adenomas (3) and carcinomas (2). In males, there were also 3 trichoepitheliomas, 1 pilomatricoma, 1 basal cell tumor, and 1 malignant melanoma. Of the 8 epithelial neoplasms in females, there were 3 squamous cell carcinomas, 2 keratoacanthomas, and 1 each basal cell tumor, malignant melanoma, and trichoepithelioma. There were 21 mesenchymal neoplasms in males and 15 in females. The most frequent neoplasm was fibroma (7 males, 8 females) followed by lipoma (7 males, 4 females) and fibrosarcoma (4 males, 3 females). One male had a liposarcoma and 2 males each had hemangioma. The total neoplasm incidence of 70/717 (9.8%) in males and 23/716 (3.2%) in females showed that skin neoplasms were 3 time more common in males than in females. Epithelial neoplasms of the skin were 6 times more common in males than in females. Males were more than twice as likely to have epithelial rather than mesenchymal skin neoplasms whereas the reverse was seen in females.

Aging↗

Intraoperative ultrasound in the management of liver neoplasms.

The purpose of this study was to determine the impact of intraoperative ultrasound (IOUS) on the management of patients with neoplasms of the liver. Fifty-nine patients with liver neoplasms (primary, 6; metastatic, 53) and without pre- or intraoperative evidence of extrahepatic disease underwent laparotomy for possible liver resection. Preoperative imaging studies included external ultrasound (n = 12), magnetic resonance imaging (n = 11), and/or computed tomography (n = 57). Intraoperative evaluation on all patients included inspection, bimanual palpation, and ultrasonography. External ultrasound, magnetic resonance imaging, and computed tomography identified all intraoperatively confirmed liver neoplasms in 33, 45, and 67 per cent of cases, respectively. Unsuspected neoplasms were identified in 12 patients (20%) by inspection/palpation and in 19 patients (32%) by IOUS. In eight patients (14%), the occult neoplasms were identified only IOUS, and in one patient the neoplasms were identified only by inspection/palpation. Occult neoplasms identified by IOUS were characterized by small size (less than 2 cm). Findings from the intraoperative evaluation, such as unsuspected neoplasms and vascular proximity or invasion, altered the preoperative plan in 20 (34%) patients. Inspection, and particularly palpation, identifies a number of preoperatively unsuspected liver neoplasms. Intraoperative ultrasound, however, is the most sensitive method for detection of liver neoplasms and influences the operative management in a substantial number of patients.

Colorectal Neoplasms↗

Association between ATL and non-hematopoietic neoplasms.

A high incidence of multiple primary neoplasms has been observed in our patients with ATL in comparison to persons with other forms of hematologic malignancy who we have observed during the past 23 years (1963-1985). Five of 15 patients with ATL (33.3 per cent) have had at least one other associated neoplasm in comparison to only 44 of 1156 patients with other forms of hematological malignancy (3.8 per cent). The incidence figures for secondary neoplasms associated with the other hematologic malignancies were 4.3 per cent (16/370) for acute non-lymphocytic leukemia (ANLL), 2.2 per cent (2/90) for acute lymphocytic leukemia (ALL), 4.8 per cent (1/21) for acute unclassifiable leukemia, 2.2 per cent (5/225) for chronic myelogenous leukemia, 4.7 per cent (2/43) for chronic lymphocytic leukemia, 5.9 per cent (8/136) for malignant monoclonal gammopathy and 3.7 per cent (10/271) for malignant lymphoma. The incidence of multiple neoplasms in patients with ATL in comparison to those with other hematological malignancies was statistically significant (p < 0.01 or p < 0.001). The neoplasms associated with ATL have been adenocarcinoma of the thyroid or stomach, and squamous cell carcinoma of the larynx, lip or lung. We identified ATL-derived factor (ADF) in the cytoplasm of the secondary neoplasms of the ATL patients by means of indirect immunofluoroscopy and immunohistochemical techniques utilizing anti-ADF antibody. We also identified ras p21 products in these neoplasms by means of p21 ras monoclonal antibody studies. The possibility that HTLV-I was the cause of the secondary neoplasms thus was investigated. HTLV-I provirus genome was not found in all the six cases of non-ATL leukemic cells of the patients with anti-HTLV-I antibodies as determined by means of Southern blot analysis utilizing pX DNA probe. These findings suggest that there is some association between ATL cells and pre-malignant cells through ADF or other unknown factors in the activation of ras oncogenes. Subsequent suppression of host immune defence mechanisms in ATL patients permits evolution of the secondary neoplasms.

Adenocarcinoma↗

N-methyl-N'-nitro-N-nitrosoguanidine-induced neoplasms in medaka (Oryzias latipes).

To test the sensitivity of the small fish species Oryzias latipes to the direct-acting carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), medaka were exposed at 15 days of age to 30 mg/L for 1 hr and followed for up to 16 mo. One hundred neoplasms were diagnosed in 84 of 213 exposed fish, with approximately equal percentages in males and females. Many neoplasms (62%) were of mesenchymal origin and were categorized as blood vascular neoplasms (hemangioma and hemangiosarcoma), invasive sarcomas, and scale-associated neoplasms. Invasive sarcomas included rhabdomyosarcoma, fascial sarcoma, hemangiopericytoma, and undifferentiated sarcoma. A scale-associated neoplasm, termed lepidocytoma, was an unusual neoplasm of scale anlage. Thyroid follicular neoplasms, with a 100% incidence in males, and pancreatic acinar carcinoma were the most common epithelial tumors. Neoplasms of the gills, swim bladder, and olfactory epithelium were also seen as well as teratoma with mixed epithelial and mesenchymal components. The study showed a broad range of neoplasms induced by MNNG in medaka, with a tissue distribution that might support direct action on exposed tissues.

Animals↗

[Prognostic analysis of 151 patients with maxillary sinus malignant neoplasms].

BACKGROUND & OBJECTIVE: Five-year survival rate of patients with maxillary malignant neoplasms is low, the prognostic factors of these neoplasms were unclear. This study was to investigate prognostic factors of maxillary sinus malignant neoplasms. METHODS: Records of 151 inpatients with malignant neoplasms of maxillary sinus initially treated at Cancer Center of Sun Yat-sen University from Sep. 1983 to Mar. 1999 were reviewed. Of 151 cases, 72 were squamous cell carcinoma (SCC), 44 were adenocarcinoma, 16 were sarcoma, and 19 were other histological types; according to 1997 UICC classification, 7 were stage II, 55 were stage III, and 89 were stage IV; 66 patients received combined therapy of surgery and radiotherapy, 14 received surgery alone, 25 received radiotherapy alone, 39 received other treatments, and 7 gave up treatment. All patients were followed up for more than 5 years. Influences of clinicopathologic factors on prognosis of patients with maxillary sinus malignant neoplasms were analyzed by Kaplan-Meier method, and Cox regression model with SPSS10.0 software. RESULTS: Five-year overall survival rate of patients of </=40 years old was 55.7%, that of patients of >40 years old was 33.3%(P=0.030); that of patients with SCC was 30.2%, of patients with adenocarcinoma was 57.5%, of patients with sarcoma was 24.3%, of patients with tumor of other histological types was 50.7% (P=0.011); that of patients with tumor of stage II, III, and IV were 85.7%, 45.8%, and 32.7%, respectively (P=0.029); that of patients with cervical metastases was 14.4%, of patients without cervical metastases was 44.1% (P=0.005); that of patients with distant metastases was 14.3%, of patients without distant metastases was 41.1% (P=0.011); that of patients without treatment was 14.3%, of patients treated with surgery alone was 42.9%, of patients treated with radiotherapy alone was 32.3%, of patients treated with combined therapy of surgery and radiotherapy was 50.8%, of patients treated with other treatments was 29.1% (P=0.004). Univariate survival analysis showed that the above 6 factors were prognostic factors of patients with maxillary sinus malignant neoplasms. Multivariate analysis showed that combination of surgery and radiotherapy (P=0.004, OR< 1), clinical stage (P=0.025, OR >1), SCC (P=0.016, OR >1), and sarcoma (P=0.003, OR >1) were independent prognostic factors of patients with maxillary sinus malignant neoplasms. CONCLUSION: For maxillary sinus malignant neoplasms, patients with SCC or sarcoma had poorer survival than patients with adenocarcinoma or other histological types of tumor; patients with sarcoma had poorer survival than patients with SCC. The higher the patient's clinical stage was, the worse his prognosis was. Combination of surgery and radiotherapy may be the best treatment for patients with maxillary sinus malignant neoplasms.

Adolescent↗

Small bowel tumors: an analysis of tumor-like lesions, benign and malignant neoplasms.

The clinical records of 72 patients with 73 small bowel tumors diagnosed over a period of 25 years were reviewed. The tumors consisted of 23 tumor-like lesions, 17 benign neoplasms and 33 malignant neoplasms, the mean size of which were 2.1 cm, 5.2 cm and 7.7 cm in diameter, respectively. The tumor-like lesions and benign neoplasms were found even in children, while the malignant neoplasms were observed in patients 43 years old or over. The most common tumor-like lesion was aberrant pancreatic tissue. The common benign neoplasms were leiomyoma, lipoma and adenoma. The malignant neoplasms consisted of adenocarcinoma, malignant lymphoma and leiomyosarcoma. Regardless of tumor type or tumor location, the lesions 4 cm or larger often caused abdominal symptoms. Most of the lesions less than 4 cm caused no symptoms, but the malignant lesions of this size in the ileum elicited abdominal symptoms in all patients. The presence of lesions was diagnosed preoperatively in 26.1% of patients with tumor-like lesions, 47.1% with benign neoplasms and 48.5% with malignant neoplasms. Resection was performed in all but one patient with tumor-like lesions and benign neoplasms. Among malignant lesions, the resectability rate was 80.0% for adenocarcinoma and 100% for both malignant lymphoma and leiomyosarcoma. However, the patients with malignant lesions showed a poor prognosis. In conclusion, it is important to recognize small bowel tumors--especially malignant lesions--as a rare but possible cause of abdominal symptoms and thereby to contribute to the early detection and successful management of small bowel tumors.

Adenocarcinoma↗

Trends in survival of childhood malignancy for the past three decades. II: Neoplasms of the respiratory, skeletal, genital, skin and endocrine organs and malignant teratomas. The Committee for the Studies of the Treatments and the Biological Characteristics of Childhood Cancers.

Survival of childhood neoplasms has improved considerably during the past three decades. Improvement in survival rate for relatively infrequent neoplasms was assessed based on data obtained from the largest children's hospital in Japan. Using the data of the cancer registry of the hospital which recorded all the patients from 1965 to 1993 totalling 1026 cases, survival rate was analyzed for each type of neoplasm categorized by the S-classification for Childhood Neoplasms, a modification of the International Classification of Diseases. Survival was assessed for three 10 year periods from 1965 for infrequent neoplasms and for two 15 year periods for rare neoplasms. Improvement of survival was considerable in the neoplasms of the respiratory organs, genital organs and germ cell tumors, moderate in bone tumors and poor in the muscle and connective tissues. In conclusion, in some types of relatively infrequent neoplasms, survival improved considerably. But in soft parts and connective tissues (mostly rhabdomyosarcoma) improvement of survival was poor.

Bone Neoplasms↗

Ulceration as a possible link between duodenogastric reflux and neoplasms in the stomach of rats.

BACKGROUND: Duodenogastric reflux predisposes to gastric cancer. This study investigates whether ulceration induced by duodenogastric reflux is associated with the development of neoplasms in the stomach. MATERIALS AND METHODS: In a rat experiment, duodenal fluid was directed into the corpus (jejunal reflux) or through the pylorus into the antrum (pyloric reflux). Sham-operated animals served as controls. The animals were sacrificed after 24, 36, or 52 weeks. RESULTS: Ulcerations and neoplasms occurred more frequently in the corpus than in the antrum. In the corpus, ulceration was observed significantly more often in animals with jejunal reflux (62, 55, and 53% at 24, 36, and 52 weeks, respectively) than in animals with pyloric reflux (15, 21, and 30%). The incidence of neoplasm in the corpus increased significantly with time from 38% at 24 weeks to 89% at 52 weeks in animals with jejunal reflux and from 12 to 33% in animals with pyloric reflux. Ulceration and neoplasms shared location in the corpus adjacent to the gastrojejunostomy and by 24 weeks, all but one neoplasm in the jejunal reflux and one in pyloric reflux groups occurred adjacent to ulceration. In the antrum, 37% of the animals had a prepyloric ulceration after 24 weeks of pyloric reflux and only one of these animals had a neoplasm. By 52 weeks 20% of animals with pyloric reflux had a neoplasm that appeared in the prepyloric area. CONCLUSIONS: Ulceration and neoplasm occurred at the same sites in the stomach, and ulcerations preceded the development of neoplasms in the antrum and very likely in the corpus. The results suggest that ulceration plays an important role in the genesis of neoplasms in the stomach and that the vulnerability to duodenogastric reflux is more pronounced in the corpus than in the antrum mucosa.

Adenocarcinoma↗

Point mutations of K-ras and H-ras genes in forestomach neoplasms from control B6C3F1 mice and following exposure to 1,3-butadiene, isoprene or chloroprene for up to 2-years.

1,3 Butadiene (BD), isoprene (IP) and chloroprene (CP) are structural analogs. There were significantly increased incidences of forestomach neoplasms in B6C3F1 mice exposed to BD, IP or CP by inhalation for up to 2-years. The present study was designed to characterize genetic alterations in K- and H-ras proto-oncogenes in a total of 52 spontaneous and chemically induced forestomach neoplasms. ras mutations were identified by restriction fragment length polymorphism, single strand conformational polymorphism analysis, and cycle sequencing of PCR-amplified DNA isolated from paraffin-embedded forestomach neoplasms. A higher frequency of K- and H-ras mutations was identified in BD-, IP- and CP-induced forestomach neoplasms (83, 70 and 57%, respectively, or combined 31/41, 76%) when compared to spontaneous forestomach neoplasms (4/11, 36%). Also a high frequency of H-ras codon 61 CAA-->CTA transversions (10/41, 24%) was detected in chemically induced forestomach neoplasms, but none were present in the spontaneous forestomach neoplasms examined. Furthermore, an increased frequency (treated 13/41, 32% versus untreated 1/11, 9%) of GGC-->CGC transversion at K-ras codon 13 was seen in BD-, and IP-induced forestomach neoplasms, similar to the predominant K-ras mutation pattern observed in BD-induced mouse lung neoplasms. These data suggest that the epoxide intermediates of the structurally related chemicals (BD, IP, and CP) may cause DNA damage in K-ras and H-ras proto-oncogenes of B6C3F1 mice following inhalation exposure and that mutational activation of these genes may be critical events in the pathogenesis of forestomach neoplasms induced in the B6C3F1 mouse.

Animals↗

Predominant K-ras codon 12 G --> A transition in chemically induced lung neoplasms in B6C3F1 mice.

Based on long-term toxicity and carcinogenicity studies in B6C3F1 mice conducted by the National Toxicology Program, 2,2-Bis(bromomethyl)-1,3-propanediol (BMP) and tetranitromethane (TNM) have been identified as carcinogens. Following 2 yr of exposure to 312, 625, or 1,250 ppm BMP in feed, or exposure to 0.5 or 2 ppm TNM by inhalation, increased incidences of lung neoplasms were observed in B6C3F1 mice at all exposure concentrations compared to unexposed mice. The present study characterizes genetic alterations in the K-ras protooncogene in BMP- and TNM-induced lung neoplasms, respectively, and compares the findings to spontaneous lung neoplasms from corresponding control mice. The frequencies of the K-ras mutations were 57% (29/51) in BMP-induced lung neoplasms compared to 15% (3/20) in lung neoplasms from dosed feed control mice, and 54% (14/26) in TNM-induced lung neoplasms compared to 60% (3/5) in lung neoplasms from inhalation control mice. G --> A transitions at the second base of the K-ras codon 12 (GGT --> GAT) were the most frequent pattern of K-ras mutations identified in BMP-induced (20/29) and TNM-induced lung neoplasms (13/14), which differed from the mutational patterns identified in the lung neoplasms from unexposed control mice. These results indicate that mutations in the K-ras gene are involved in B6C3F1 lung carcinogenesis following BMP- and TNM-exposure, and the high frequency and specificity of the ras mutation profile in lung neoplasms (G --> A transition) may be due to in vivo genotoxicity by the parent compounds or their metabolites.

Animals↗

Classification of feline intraocular neoplasms based on morphology, histochemical staining, and immunohistochemical labeling.

The objectives of this study were to evaluate morphologic, histochemical, and immunohistochemical characteristics of well-differentiated and anaplastic intraocular neoplasms of cats, and to develop a diagnostic algorithm for, and investigate the association of ruptured lenses with these neoplasms. Seventy-five feline globes with intraocular neoplasms were stained with hematoxylin and eosin and examined by light microscopy. Morphologic diagnoses included 33 intraocular sarcomas, 17 diffuse iris melanomas, 15 lymphosarcomas, three ciliary adenomas, one metastatic carcinoma, and six undifferentiated intraocular neoplasms. Sections of these globes were then stained with periodic acid Schiff (PAS), and immunohistochemical (IHC) labels for various cellular markers. Histochemical staining and IHC labeling confirmed cellular differentiation in 73/75 neoplasms but was discordant with morphologic diagnoses in 8/75. These included four neoplasms morphologically diagnosed as lymphosarcomas but which expressed differentiation antigens consistent with melanoma (n = 3) or ciliary adenocarcinoma (n = 1), and four tumors morphologically diagnosed as intraocular sarcomas that expressed differentiation antigens for melanoma (n = 2), metastatic carcinoma (n = 1), or remained undifferentiated (n = 1). Immunohistochemical labeling suggested a diagnosis in 5/6 morphologically undifferentiated neoplasms including one intraocular sarcoma, two diffuse iridal melanomas, and two ciliary adenocarcinomas. Based upon morphologic, histochemical, and IHC characterization, ruptured lens capsules were detected in 28/30 intraocular sarcomas, 3/24 diffuse iris melanomas and 1/11 lymphosarcomas, but not in ciliary epithelial neoplasms, metastatic carcinomas, or undifferentiated intraocular neoplasms. An algorithm is provided that facilitates stain and IHC label selection for differentiating anaplastic intraocular feline neoplasms.

Adenoma↗

Clinical and cytologic features of papillary neoplasms of the breast.

OBJECTIVE: To compare the cytologic features benign and malignant papillary breast lesions. STUDY DESIGN: We reviewed the clinical and cytologic features in 29 cases of intraductal papilloma and 26 cases of atypical papilloma or papillary carcinoma that had been diagnosed by histologic examination. The diameter of the mass was examined as a clinical feature. The cytologic features evaluated were as follows: bloody background, row of tall columnar cells, naked bipolar nuclei, hemosiderin-laden macrophages, myoepithelial cells, single scattered atypical cells, cellularity, nuclear atypia, nuclear grade, apocrine metaplasia, eosinophilic cytoplasmic granules, papillary clusters, small papillae, cell balls and large sheets. RESULTS: Of the features evaluated, the diameter of the mass, naked bipolar nuclei and cell balls differed significantly between benign and atypical or malignant papillary neoplasms. The average diameter of a benign papillary neoplasm was 1.8 cm, and that of an atypical or malignant papillary neoplasm was 2.2 cm (p = 0.042). Naked bipolar nuclei were found in 27 cases of benign papillary neoplasm (93.1%) versus 19 cases of atypical or malignant papillary neoplasm (73.1%) (p = 0.050). Cell balls were found in 14 (48.3%) and 21 (80.8%) cases, respectively (p = 0.012). All 6 cases in which cell balls were present and naked bipolar nuclei were absent proved to be atypical or malignant papillary neoplasms. Of 17 cases in which cell balls were absent and naked bipolar nuclei present, 13 (76.5%) were benign papillary neoplasms. CONCLUSION: Most cytologic features overlapped in benign and atypical or malignant papillary neoplasms. Although they were not pathognomonic, naked bipolar nuclei and cell balls were cytologic features that differed significantly between benign and atypical or malignant papillary neoplasms. When papillary neoplasms of the breast are suspected in a cytologic smear, the combination of clinical examination, mammography and cytologic features should be considered to make the correct diagnosis.

Biopsy↗

Proteotypic classification of spontaneous and transgenic mammary neoplasms.

INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. METHODS: Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm.

Animals↗

[Difficulties of differential diagnosis of pancreatic pseudocysts and cystic neoplasms].

OBJECTIVE: Surgical resection is indicated in potentially malignant pancreatic cystic neoplasms. Drainage operations are performed in large (5-6 cm) and/or symptomatic pseudocysts. Misdiagnosis results in a considerable delay in an appropriate treatment. Our aims were to compare clinical, morphological, biochemical features of cystic neoplasms and pseudocysts, in which diagnosis of cystic neoplasm was suspected preoperatively, and to determine characteristics, which could predict the misdiagnosis of cystic neoplasms as "pseudocysts". MATERIAL AND METHODS: One hundred and thirty four patients were operated because of pancreatis cystic lesions (22 cystic neoplasms and 112 pseudocysts) between January 1999 and May 2004. Two groups of patients were evaluated retrospectively. Group I included 22 (10 serous and 8 mucinous cystoadenomas, 3 mucinous cystadenocarcinomas, 1 solid papillary tumor) resected neoplasms. Group II included 11 patients in whom neoplasm was suspected during investigation, but definitive diagnosis of pseudocyst was established. Clinical manifestation, morphologic characteristics and data of instrumental investigations were also compared. Preoperative and postoperative diagnoses were compared with histopathological findings. RESULTS: Women predominated in group I (67.2%) and men in group II (81.2%). Group I patients were older (mean age 57.9+/-14.55 versus 49.27+/-10.07 years). All pseudocysts were symptomatic. Two (9.1%) incidental cystic neoplasms and 2 drainage operations were performed previously because of misdiagnosed "pseudocysts" in other hospitals. Abdominal pain, 81.8% and 100%, and abdominal mass, 31.8% and 54.4%, were recorded most frequently, group I and group II respectively. Neoplasms (median diameter 59.6 mm) were mainly located in pancreatic head (31.8%) and body (36.4%). Most of pseudocysts (median diameter 71.1 mm) were located in pancreatic head (45.5%). Diagnostic sensitivity of ultrasonography (86.4%) and computed tomography scan (84.2%) was higher in group I than in group II (63.6% and 77.8%). Two serous oligocystic and 1 mucinous cystoadenomas were misdiagnosed as "pseudocyst" preoperatively. In one case malignancy of mucinous tumor diagnosed only postoperatively. CONCLUSIONS: Differentiating serous and mucinous cystoadenomas from pseudocysts may be difficult. Malignant neoplasms may be undetermined preoperatively. Resection should always be performed in instances where findings cannot be clearly identified.

Abdominal Pain↗

[Occupational neoplasms in Poland in the years 1971-1994].

The analysis of the incidence of malignant neoplasms, recognised as occupational disease, in Poland during the years 1971-94 was based on occupational disease certificates sent obligatory to the Nofer institute of Occupational Medicine (Lódz) by all sanitary and epidemiological stations under the Ministry of Health and Social Welfare and the Polish State Railways. During the period study 1118 occupational neoplasms were diagnosed, including 1042 cases (93.2%) of neoplasms in males. Among males malignant Ineoplasms of lung (36.1%), larynx (25.5%), bladder (14.7), skin (6%), lymphatic and haematopoietic tissue (3.4%) and pleura (2.9%) were most common. The rate occupational neoplasms in the total number of neoplasms registered accounted for 0.11% in males and 0.01% in females. PAH (29.1%), asbestos dust (18.8%), ionizing radiation (13.8%), chromium and its compounds (13.5%) and benzidine (9.8%) belong to the most frequent causes of malignant neoplasms in males, and ionizing radiation (31.5%) and asbestos dust (30.3%) in females. The number of neoplasms recognised as occupational disease is very low. Underestimation of occupational neoplasms is very common throughout the world, but it is particularly high in Poland if we take the incidence of pleura mesothelioma as an example. This is mainly due to: (1) the lack of clinical and morphological specificity of occupationally induced neoplasms; (2) a long latency; (3) the influence of other factors confounding the effect of occupational exposure; (4) a relatively small number of occupational carcinogens identified thus far; (5) limited knowledge of occupational carcinogens and criteria for occupational disease certification, and unsatisfactory interviewing skills among doctors who diagnose cancer disease. The identification of a harmful factor and the size of exposure to it, belongs to the weakest point in certifying the occupational background of the disease. The essential conclusions presented stress the urgent need for establishing the system facilitating the diagnosis and certification of occupational neoplasms.

Adolescent↗

Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas.

BACKGROUND & AIMS: The aim of this study was to determine recurrence and long-term survival after resection of pancreatic intraductal papillary mucinous neoplasm and to correlate recurrence and survival with histology, extent of resection, and duration of follow-up. METHODS: A single pathologist, without knowledge of previous interpretations of histology or clinical data, retrospectively reviewed and classified 113 resected intraductal papillary mucinous neoplasms as invasive carcinoma (n = 40) or as noninvasive neoplasms (adenoma, borderline, or carcinoma in situ; n = 73). Data on recurrence (locoregional or metastatic), follow-up, and cause of death were obtained from patient records and/or by contacting patients and their physicians. RESULTS: In invasive intraductal papillary mucinous neoplasm, recurrence was similar after partial pancreatectomy (18/27; 67%) and total pancreatectomy (8/13; 62%) and occurred within 3 years of resection in 91%. Among noninvasive neoplasms, 5 of 60 (8%) recurred after partial pancreatectomy (median follow-up, 37 months); none recurred after total pancreatectomy (n = 13; median follow-up, 32 months). Recurrence after resection in noninvasive neoplasms was diagnosed after a median of 40 months (range, 23-75 months); recurrence was noninvasive in 3 and invasive cancer in 2. Five-year survival was better for noninvasive compared with invasive intraductal papillary mucinous neoplasm (84.5% vs. 36%; P < 0.001). CONCLUSIONS: Invasive intraductal papillary mucinous neoplasm recurs frequently even after a complete "curative" resection and portends poor survival. In contrast, noninvasive intraductal papillary mucinous neoplasm recurs infrequently after resection, and survival is excellent regardless of the degree of epithelial dysplasia in the tumor.

Adenocarcinoma, Mucinous↗

Spontaneous skin neoplasms in Long-Evans rats.

Two hundred sixty-one neoplasms involving the skin and its appendages were observed in a total of 980 (490 of each sex) Long-Evans (LE) control rats of 7 carcinogenicity studies. All studies were 2 yr in duration and were conducted in the years 1983 through 1994. Skin neoplasms were reevaluated and classified according to current criteria and nomenclature. The various neoplasm incidences were compared to those published for Sprague-Dawley (SD), Fischer-344 (F-344), and Wistar rats. The most common neoplasms involved the mammary glands, affecting 28% of LE females. This incidence is comparable to the 31% incidence reported for SD females. Mammary gland fibroadenomas were observed in 22% of LE females compared to 19-31% of SD, 7-29% of F-344, and 4-25% of Wistar females. Mammary gland adenocarcinomas occurred in 7% of LE females in our laboratory, while incidences of 9-17% of SD, 0-2% of F-344, and 1-13% of Wistar females are reported. In LE males, the incidences of mammary gland fibroadenomas (1%) and adenocarcinomas (0.6%) were comparable to the 0-3% reported recently in other strains. As is observed in other strains, the incidence of nonmammary gland skin neoplasms in LE males (11.4%) was greater than the incidence in females (2.7%). Fibromas were the most common nonmammary gland skin neoplasm and affected 3.3% of males and 0.6% of females. The incidences of fibromas in SD, F-344, and Wistar rats range from 0-7%, 0-3.2%, and 0-12%, respectively, in males and from 0-3.3%, 0-1.1%, and 0-4%, respectively, in females. Of the 4 strains, only SD males have more nonmammary gland epithelial than mesenchymal skin neoplasms. The difference between the LE and SD males can be attributed to the criteria used to classify keratoacanthomas. Only one keratoacanthoma was observed in LE rats in this review. Reevaluation of skin neoplasms found in 980 LE control rats and comparison of the resulting incidences with those of other strains demonstrated that most skin neoplasms in LE rats have comparable incidences to those reported for SD, F-344, and Wistar rats.

Animals↗