p53 protein in benign and malignant sweat gland tumors.

Mutation of the p53 gene and increased levels of p53 protein are among the most frequent alterations in human cancers. To date, very little is known about the mechanisms underlying the development of sweat gland carcinomas. In this study, we analyzed 43 benign and 39 malignant sweat gland tumors for p53 protein level using the antibody PAB1801. Nine (23%) of 39 sweat gland carcinomas were positive for p53 protein. Among these carcinomas, six of 12 cases of extramammary Paget's disease were positive using immunohistochemistry. No other correlation between tumor subtype and p53 reactivity was detected. Among 43 benign sweat gland tumors, only one case displayed staining for p53. We conclude that p53 protein plays a role in a subset of sweat gland tumors, especially in extramammary Paget's disease.

[Hypervariable regions (HVR) as genetic markers in tumor diagnosis. Methodological principles and their use in pathologic diagnosis]. / Hypervariable Regionen (HVR) als genetische Marker in der Tumordiagnostik. Methodische Grundlagen und ihre Anwendung in der pathologischen Diagnostik.

Variable number tandem repeats (VNTR) are highly polymorphic DNA sequences which can be used as genetic markers in different fields of medicine. In this report, we describe the methodology of VNTR in diagnostic molecular pathology, using a rapid, DNA-based approach involving polymerase chain reaction (PCR) amplification and electrophoresis of highly polymorphic DNA satellite sequences. As concrete examples of the application of this approach, we present two case reports: 1. A B-cell lymphoma of the porta hepatis developed in a 54-year-old man 4.5 months after orthotopic liver transplantation for liver failure due to chronic hepatitis C infection. Using DNA polymorphisms as genetic markers, we showed that the tumor was of donor origin. This finding may be important for the patient's subsequent management. 2. An immature teratoma of the left ovary was found during delivery by cesarean section in a 27-year-old woman. The female newborn survived for 9 weeks and then died from central dysregulation because of an intracranial immature teratoma. Because the synchronous tumors were of similar histology, clonal origin in maternal tissues and metastatic spread were initially suspected. Analysis of highly polymorphic DNA markers clearly indicated that the teratoma carried by the child was of independent genetic origin from the mother's tumor.

[DNA ploidy and prognosis of cardia and stomach carcinomas. A comparative flow and image cytometric analysis pf paraffin-embedded tumor sections]. / DNA-Ploidie und Prognose der Kardia- und Magenkarzinome. Eine vergleichende fluss- und bildzytometrische Untersuchung an paraffin-eingebetteten Tumorresektaten.

The prognostic relevance of DNA stem line ploidy was ascertained by comparative DNA analysis performed by flow cytometry (FCM) and by Feulgen image cytometry (ICM) of histologic slides on paraffin-embedded resection material from 221 carcinomas of the cardia and stomach. While flow cytometric detection of DNA stem line aneuploidy was rather insecure in smaller or diffuse carcinomas, the methodological restrictions of ICM were seen in a reduced measuring accuracy varying from one case to the other. This resulted in a lower security in distinguishing mere peridiploidy from real hyperdiploid DNA aneuploidy. Despite the difference of methodology, the results were principally concurring. The assessment of DNA stem line ploidy offered no appreciable information about the prognosis of Lauren's diffuse carcinomas. For intestinal carcinomas, however, there was a significant positive correlation between DNA stem line aneuploidy and the evidence of regional nodal metastases, which might explain to a considerable extent the significantly unfavorable clinical course of tumor cases with recorded DNA aneuploidy. The correlation between DNA stem line ploidy, nodal status, and clinical outcome was distinctly less strong in intestinal carcinomas of the cardia than in those of the stomach, because nodal metastatic spread of cardia carcinomas is strongly influenced by local conditions of lymph drainage and the special mechanical strain.

Immature teratomas of different origin carried by a pregnant mother and her fetus.

We describe the case of a pregnant mother and her fetus who both carried teratomas during the pregnancy. The fetus was diagnosed at 38 weeks' gestation to have an intracranial mass, which was later determined to be an immature teratoma. During a cesarean section delivery, an ovarian tumor was found in the 27-year-old mother that was also diagnosed to be an immature teratoma. Because of the similar histology of the tumors carried by both mother and child, a single clonal origin was suspected. Using polymerase chain reaction (PCR) and electrophoresis of highly polymorphic DNA satellite sequences, we determined that the origin of the intracranial teratoma carried by the child was independent of the mother's tumor. We also examined the p53 tumor suppressor gene in constitutional cells from both mother and child for the possible presence of a cancer-predisposing inherited mutation, but none was found. To our knowledge, this is the first report of the simultaneous occurrence of independent malignant immature teratomas in a mother and child during pregnancy.

Comparative studies of cardia carcinoma and infracardial gastric carcinoma.

In a part retrospective, part prospective study, 354 carcinomas of the cardia were compared with 1259 infracardial gastric carcinomas with regard to the age and sex of the patients, macroscopic classification, microscopic classifications, depth of invasion, and survival rates. Mortality rates are generally higher in cardia carcinoma than in stomach carcinoma. The difference is due to the significantly poorer survival of cardia carcinoma patients in stage I, while mortality rates in stages II, III, and IV of both types are approximately similar. Highly significant differences were also found with regard to sex ratio, incidence of macro- and microscopic subtypes, and invasive growth. The typical cardia carcinoma occurs preferentially in men, is mostly well-delineated, and is manifested as an ulcerated or polypoid, well-differentiated tumor of expansive growth, corresponding to Laurén's intestinal type. These results confirm the concepts of McPeak and Warren, MacDonald, and Siewert et al., that the carcinoma located in the cardia must be seen as a separate entity of gastric carcinoma.

Adenocarcinomas of esophagus and cardia in comparison with gastric carcinoma.

Since the carcinomas of the cardia and the adenocarcinomas of the esophagus show many similarities in their histological and morphological descriptions, a detailed comparative study was attempted on the basis of 66 esophageal carcinomas in adenoid differentiation, 359 carcinomas of the cardia, 1288 gastric carcinomas in infracardial localisation, and 492 squamous carcinomas of the esophagus. The evaluation yielded no significant differences between the adenocarcinomas of the esophagus and the cardia neither in age and sex distribution nor with regard to the classifications of Borrmann, WHO, Ming, and Laurén, but a significant discrimination was possible between esophageal and cardial adenocarcinoma together, on the one hand, and infracardial gastric carcinoma on the other. Furthermore, esophageal adenocarcinomas were localized preferentially in the lower third, unlike squamous carcinomas of the same organ. These results suggest that esophageal adenocarcinoma and carcinoma of the cardia must be considered as one separate entity, probably originating from a common stem cell. They further suggest that the cardia belongs to the esophagus rather than to the stomach.

[Risk of cancer following cholecystectomy, hysterectomy or appendectomy]. / Untersuchungen zum Krebsrisiko nach früherer Cholezystektomie, Hysterektomie oder Appendektomie.

Patients with previous cholecystectomy, hysterectomy or appendectomy have an increased risk of developing cancer of other organs such as the bowel, breast kidney or ovary, particularly if they have undergone more than one operation. Previous nephrectomy, strumectomy, prostatectomy or gastric resection for gastroduodenal ulcer do not increase the risk of bowel cancer.

Sequence analysis of polymerase chain reaction amplified t(14;18) chromosomal breakpoints in formalin fixed, paraffin wax embedded follicular lymphoma.

AIMS: To determine whether junctional sequences of rearranged chromosomes can be amplified by use of the polymerase chain reaction (PCR) and whether direct sequence analysis of the PCR products is possible, using DNA from formalin fixed, paraffin wax embedded biopsy specimens. METHODS: DNA was extracted from paraffin wax embedded, formalin fixed lymphoma specimens, and junctional sequences of rearranged chromosomes were amplified by the PCR. The products were used as templates for asymmetrical PCR. Subsequently, direct sequence analysis was performed using the chain termination method. RESULTS: Formalin fixed, paraffin wax embedded biopsy specimens and PCR amplification could be used to determine the nucleotide sequences of junctional regions of rearranged chromosomes t(14;18) from patients with follicular lymphoma. CONCLUSION: The identification of junctional sequences of the translocation in follicular lymphoma provides a molecular "fingerprint" of t(14;18) of the lymphoma of an individual patient and can be used for the detection of clone specific DNA in any biopsy tissue obtained from the patient. The strategy used for rapid sequence analysis of PCR amplified DNA sequences will be useful in many areas of molecular pathology.

[Central nervous findings in neurofibromatosis]. / Zentralnervöse Befunde bei Neurofibromatose.

Neurofibromatosis (NF) is subdivided into at least two different forms: NF-1, which is characterized by café-au-lait spots, cutaneous neurofibromas, Lisch nodules and osseous dysplasias, and NF-2, the hallmarks of which are bilateral acoustic neuromas. Neuropathological findings in 5 cases of NF-1 and 3 cases of NF-2 are presented.

Congenital cystic adenomatoid malformation of the lung associated with bile duct hypoplasia.

Congenital cystic adenomatoid malformation (CCAM) is a rare lesion that affects one or two lobes of the lung. Infants are either stillborn or die shortly after birth if therapy is not started immediately. The lesion itself may be solid or cystic, manifesting in an adenomatoid increase in terminal respiratory structures. Clinical, pathological and radiological findings of a child prematurely born are presented. A special feature in this case was hypoplasia of intrahepatic bile ducts, an unusual association with CCAM that has not been previously reported. Pathogenesis and embryological connotations of the two lesions are discussed. The importance of prenatal diagnosis and immediate surgical therapy after birth is stressed.

Association of macrophages detected with monoclonal antibody 25 F 9 with progression and pathobiological classification of gastric carcinoma.

Using monoclonal antibody 25 F 9, which reacts with a determinant of mature macrophages, the inflammatory infiltrate of 66 gastric carcinomas was evaluated using a counting grid. The ratio tumor cells/macrophages was determined for every tumor. For a threshold value of 5, carcinomas with a better prognosis, such as the intestinal type according to Lauré, the expanding type according to Ming and the differentiated carcinomas according to the WHO had a significantly smaller relative content of 25 F 9-positive macrophages (a minimum of P less than 0.05) than the diffuse type, infiltrative type, and undifferentiated carcinomas. Furthermore, the relative macrophage content tended to increase with the stage of carcinomas spread (P less than 0.1). The results suggested that 25 F 9-positive macrophages in gastric carcinoma are of greater significance in tumor spread than in any defensive reaction against the tumor.

Isolation and characterization of the fatty acid binding protein from human heart.

We have isolated in pure form a fatty acid binding protein (FABP) from human cardiac muscle. After preparation of a 100,000 g supernatant fraction, the procedure required only one gel chromatographic (Sephacryl S 200) and two cation exchange (CM-Sephadex C 50) steps. The recovery of FABP was 55%. Pure FABP (12.5 mg) was obtained from a 1-g of dry powder equivalent of the high-speed supernatant. The protein had an Mr of 15,500 +/- 1,000 Da and an isoelectric point of 5.3. The properties of human cardiac FABP, i.e., molecular mass, isoelectric point, amino acid composition, ultraviolet spectrum, and affinities for hydrophobic ligands, were close to those found for FABPs from bovine heart (Jagschies et al. 1985. Eur. J. Biochem. 152: 537-545). In addition, immunological cross-reactivities showed a relationship between FABPs from several mammalian heart tissues. The data elaborated by us and others support the existence of a cardiac-type FABP that is distinct from the well-defined hepatic-type and gut-type FABPs.

[The significance of pelvic lymph-node status in prostatic cancer]. / Die Bedeutung des Beckenlymphknotenstatus beim Prostatakarzinom.

The formation of metastases of carcinoma of the prostate has become more significant since the introduction of en-bloc pelvic lymphadenectomy using the serial-cut method. Lymphogenous evacuation of the pelvis occurs increasingly with advanced and dedifferentiated primary tumours. However, it can be found with low categories of tumours and differentiated carcinomas. pLA is superior to all other procedures for N-determination. If suitably indicated it allows a localized tumour process to be confirmed. Lymphatic oedemas are the most frequent complications. These can be largely avoided by retention of lacunary lymph nodes or primary fitting of lympho-nodo-venous anastomoses.

Human lymphocyte response to CEA: titration of different CEA samples and neutralization experiments with monoclonal anti-CEA antibodies.

By means of the macrophage electrophoretic mobility technique a striking digestive system cancer-associated human lymphocyte response to CEA has been found during a large-scale study including tests in 499 individuals. The question to be answered by this study was whether this response is really CEA-specific. Titration experiments with 3 different CEA preparations in lymphocytes from 5 colorectal cancer patients showed that the threshold dose of CEA necessary to induce lymphocyte responses amounts to 50-100 ng CEA per ml and 10(6) lymphocytes, regardless of the CEA origin and its state of purity. The CEA specificity of the responses was proved by neutralization experiments with 3 CEA-specific monoclonal antibodies. When allowed to react with CEA before lymphocyte incubation, the MABs prevented CEA from inducing lymphocyte responses. Appropriate murine control myeloma protein did not influence these responses. The reactivity of these lymphocyte samples to a teratocarcinoma extract could not be prevented by treating this material with CEA-specific MABs before incubation. Preliminary attempts to enrich the lymphokine(s) released after CEA stimulation resulted in recovery of the activity within 2 arbitrarily cut Sephadex G-100 fractions comprising the mol. wt range of 3000-47,000.