Apmis

STEIGEN, SONJA E.; EIDE, TOR J.; WASAG, BARTOSZ; LASOTA, JERZY; MIETTINEN, MARKKU

doi: 10.1111/j.1600-0463.2007.apm_587.xpmid: 17504295

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. This tumor typically expresses KIT, and has KIT or PDGFRA activating mutation. In this study we evaluated 89 GISTs diagnosed in Northern Norway during a 30‐year period. KIT exons 8, 9, 11, 13, and 17 were analyzed by PCR amplification and direct sequencing. Subsequently PDGRA exons 12, 14, and 18 were evaluated in KIT wild‐type cases. KIT mutations were found in 66 cases (75%), and PDGFRA mutations in 9 cases (10%). Most common were KIT exon 11 mutations, with 58 cases. Tumors with Kit exon 11 point mutations had a significantly better prognosis than those with deletions. There were five KIT exon 9 duplications, three exon 13 point mutations, and one point mutation in exon 17. There were nine PDGFGRA mutations: seven in exon 18 and two in exon 12. All but one PDGFRA mutant GISTs were gastric tumors with epithelioid morphology, and these tumors were on average smaller than those with KIT mutations. KIT and PDGFRA wild type was found in 15% of cases. Analysis of KIT and PDGFRA mutations is of significance for treatment with tyrosine kinase inhibitors, and may also have value when assessing the biological potential of GIST.

ADVANI, ABDOLREZA; DONNELLY, DECLAN; GUSTAFSSON, LENNART; HALLANDER, HANS O.

doi: 10.1111/j.1600-0463.2007.apm_556.xpmid: 17504296

In a surveillance programme undertaken from 1997 through 2004, Bordetella pertussis isolates and clinical information were collected after introduction of acellular pertussis vaccines (Pa) in 1996. Changes in the B. pertussis population were studied in three incidence peaks: 1999–2000, 2002 and 2004. Available isolates from 158 fully vaccinated children representing all of Sweden, plus 37 from the Gothenburg area 2003–2004, were analysed by pulsed‐field gel electrophoresis (PFGE), serotyping and sequencing of the virulence factor genes pertussis toxin subunits 1 and 3 (ptxA, ptxC), pertactin (prn), tracheal colonisation factor (tcfA) and fimbria3 (fim3). Allele ptxA1 was found in all isolates. There was a statistically significant increasing trend in three out of five studied genes, ptxC, prn and tcfA, and for a fourth, Fim3, if Gothenburg strains were included. The PFGE profile BpSR11 appearing in the 1999–2000 peak dominated by ≥23% during the entire period, bringing with it the allele combination 1/2/2/2/B (ptxA1/ptxC2/prn2/tcfA2/fim3B). Other BpSR11‐related profiles with the same allele combination and more than 82% similarity—BpSR5 in the 2002 peak and BpSR12 in the 2004 peak—appeared with an increasing trend. Although vaccination with Pa has reduced disease, new variants have emerged representing clones surviving in the immunized population.

CARVALHO, ANA PAULA D'ALLICOURT; VENTURA, GRASIELLA MARIA CARVALHO; PEREIRA, CAROLINA BORGES; LEÃO, ROBSON SOUZA; FOLESCU, TÂNIA WROBEL; HIGA, LAURINDA; TEIXEIRA, LUCIA MARTINS; PLOTKOWSKI, MARIA CRISTINA MACIEL; MERQUIOR, VÂNIA LUCIA CARREIRA; ALBANO, RODOLPHO MATTOS; MARQUES, ELIZABETH ANDRADE

PIPP, IRIS; WAGNER, LUDWIG; RÖSSLER, KARL; BUDKA, HERBERT; PREUSSER, MATTHIAS

doi: 10.1111/j.1600-0463.2007.apm_590.xpmid: 17504298

Secretagogin is a recently described calcium‐binding protein, which is expressed in some neurons of the human brain. In this study we systematically investigated secretagogin expression in 245 tumours of the human brain and its coverings using immunohistochemistry. We found focal or widespread secretagogin expression in tumour cells in 1/18 oligoastrocytomas, 1/19 oligodendrogliomas, 2/20 anaplastic oligodendrogliomas, 2/9 ependymomas, 2/11 anaplastic ependymomas, 2/10 glioblastomas, 3/11 gangliogliomas and 1/2 anaplastic gangliogliomas, 10/10 central neurocytomas, 5/10 classic medulloblastomas, 4/5 desmoplastic medulloblastomas, 3/5 large cell/anaplastic medulloblastomas, 3/5 neuroblastomas, 3/10 meningiomas, 2/10 haemangioblastomas, and 13/19 pituitary adenomas. Further, we observed secretagogin expression in endothelial cells in 5/10 meningiomas, 2/5 haemangiopericytomas, and 2/10 haemangioblastomas. We detected no secretagogin expression in fibrillary astrocytoma, pilocytic astrocytoma, DNT, pineocytoma, pineoblastoma, subependymal giant cell astrocytoma (SEGA), atypical teratoid/rhabdoid tumour (AT/RT), or primary central nervous system lymphoma (PCNSL). We conclude that secretagogin is differentially expressed in human neuronal, glial, and embryonal brain tumours, meningial neoplasms and pituitary adenomas. Our findings indicate that secretagogin is involved in the calcium metabolism of tumour cells and endothelial cells in a subset of neoplasms of the brain and its coverings. Anti‐secretagogin immunohistochemistry does not seem to be helpful in most differential diagnostic situations in surgical neuropathology.

DE MATOS, AUGUSTO JOSÉ FERREIRA; LOPES, CÉLIA CRISTINA CARREIRAS; FAUSTINO, AUGUSTO MANUEL RODRIGUES; CARVALHEIRA, JÚLIO GIL VALE; RUTTEMAN, GERARD ROEL; GÄRTNER, MARIA DE FÁTIMA RODRIGUES MOUTINHO

doi: 10.1111/j.1600-0463.2007.apm_544.xpmid: 17504299

Recent studies of canine malignant mammary tumours suggest that reduction of E‐cadherin and/or β‐catenin correlates with invasive behaviour and lymph node metastasis. The aims of this study were to examine the interrelationships between the expression of E‐cadherin and β‐catenin, and the relationship between the expression of E‐cadherin and/or β‐catenin and the mode of growth and metastatic capacity of canine malignant mammary tumours. 90 spontaneous malignant tumours and local and regional lymph nodes were studied. A significant relationship was evidenced between membranous expression of E‐cadherin and β‐catenin (p=0.0027), but not between E‐cadherin and cytoplasmic β‐catenin. Only E‐cadherin as a separate factor was significantly related to tumour invasion (p=0.0072) and lymph node metastasis (p=0.0001). Neither membranous nor cytoplasmic β‐catenin expression was significantly related to either of these phenomena.

RAUTIO, M.; SIPPONEN, A.; PELTOLA, R.; LOHI, J.; JOKINEN, J. J.; PAPP, A.; CARLSON, P.; SIPPONEN, P.

doi: 10.1111/j.1600-0463.2007.apm_548.xpmid: 17504300

Resin salve made from Norway spruce (Picea abies) is traditionally used in folk medicine to heal skin ulcers and infected wounds. Its antimicrobial properties were studied against certain human bacteria important in infected skin wounds. The sensitivity of the resin against Gram‐positive and Gram‐negative bacteria was studied in vitro by methods that are routinely used in microbiology laboratories. The resin salve exhibited a bacteriostatic effect against all tested Gram‐positive bacteria but only against Proteus vulgaris of the Gram‐negative bacteria. Interestingly, the resin inhibited the growth of bacteria, including methicillin‐resistant Staphylococcus aureus (MRSA) and vancomycin‐resistant enterococcus (VRE), both on agar plates and in culture media. The study demonstrated antimicrobial activity of the resin salve and provided objective evidence of its antimicrobial properties. It gives some explanations why the traditional use of home‐made resin salve from Norway spruce is experienced as being effective in the treatment of infected skin ulcers.

JEONG, EUN GOO; LEE, SUNG HAK; YOO, NAM JIN; LEE, SUG HYUNG

doi: 10.1111/j.1600-0463.2007.apm_592.xpmid: 17504301

Nucleophosmin is a nucleolar phosphoprotein that shuttles between nucleus and cytoplasm. Recent reports demonstrated that exon 12 of the nucleophosmin 1 (NPM1) gene was frequently mutated in acute myelogenous leukemias (AMLs). To see whether the NPM1 mutation occurs in other malignancies, we analyzed exon 12 of NPM1 for the detection of somatic mutations in 467 carcinomas, including 142 lung, 47 hepatocellular, 93 breast, 103 colorectal and 82 gastric carcinomas, by single‐strand conformation polymorphism assay. We also analyzed the NPM1 mutation in 142 acute leukemias, including 105 AMLs. We detected 15 NPM1 mutations in the AMLs (14.3%), but there was no NPM1 mutation in the other malignancies analyzed. Our data indicate that NPM1 exon 12 is mutated in AMLs, but not in other common human cancers, and suggest that the NPM1 mutation may not play a role in the tumorigenesis of common solid cancers.

JENSEN, TIM K.; MONTGOMERY, DONALD L.; JAEGER, PAULA T.; LINDHARDT, TINA; AGERHOLM, JØRGEN S.; BILLE‐HANSEN, VIVI; BOYE, METTE

doi: 10.1111/j.1600-0463.2007.apm_591.xpmid: 17504302

A fluorescent in situ hybridisation (FISH) assay targeting 16S ribosomal RNA was developed for detection of the zoonotic bacterium Coxiella burnetii in formalin‐fixed, paraffin‐embedded tissue, and applied on placentas from ruminant abortions. The applicability of the FISH assay was compared to immunohistochemistry (IHC) using human positive control serum in 12 cases of C. burnetii‐associated placentitis as well as 7 negative control tissue samples. In all 12 cases the bacterium was detected within trophoblasts as well as free in the placental debris by both FISH and IHC. Extensive and significant infection by C. burnetii was revealed in 10 of the cases, whereas a slighter and focal distribution of the bacterium was observed in two cases. 90 aborted placentas from Danish ruminants were investigated by FISH. C. burnetii was detected in one bovine case only, representing the first confirmation of C. burnetii in Danish animals. The study shows that FISH targeting 16S ribosomal RNA is a feasible diagnostic tool for detection of C. burnetii in tissue samples and fully comparable to IHC.

YOO, NAM JIN; LEE, SUNG HAK; JEONG, EUN GOO; LEE, SUG HYUNG

doi: 10.1111/j.1600-0463.2007.apm_632.xpmid: 17504303

Alterations of caspases, the main executioners of apoptosis, have been described in human cancers. Caspase‐9 plays a crucial role in the initiation phase of the intrinsic apoptosis pathway. Caspase‐9 is phosphorylated at Thr125 through the mitogen‐activated protein kinase (MAPK) pathway, and this phosphorylation is associated with inhibition of caspase‐9 activation. The aim of this study was to explore whether phosphorylated caspase‐9 (p‐caspase‐9) expression could be a characteristic of gastric carcinomas. We analyzed expression of p‐caspase‐9 protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. p‐caspase‐9 was detected in 33 of the 60 carcinomas (55%). Both early and advanced gastric carcinomas expressed p‐caspase‐9. There was no significant association of p‐caspase‐9 expression with clinocopathological characteristics, including invasion, metastasis and stage. In contrast to gastric cancer cells, epithelial cells in normal gastric mucosa showed no or only weak expression of p‐caspase‐9. Taken together, these results indicate that caspase‐9 is frequently phosphorylated in gastric carcinomas, and that the phosphorylation of caspase‐9 might be an inhibitory mechanism of caspase‐9‐mediated apoptosis in gastric carcinomas. Increased expression of p‐caspase‐9 in malignant gastric epithelial cells compared to normal mucosal epithelial cells suggests that p‐caspase‐9 expression might play a role in gastric carcinoma development.

CHOWDHURY, NILOTPAL; PAI, MUKTHA R.; LOBO, FLORA D.; KINI, HEMA; VARGHESE, REBECCA

doi: 10.1111/j.1600-0463.2007.apm_560.xpmid: 17504304

The present study illustrates the effect of using the consolidated total score (obtained on a 7‐point scale by adding the tubular, nuclear and mitotic scores) as well as double reporting on the interobserver reliability of breast cancer grading by the Nottingham method. 50 consecutive breast cancer slides were graded independently by 5 pathologists. The interobserver reliability between the individual pathologists for final grade, total score and grade components was estimated by quadratic weighted kappa (kw). Similarly, the inter‐observer reliability of double reported scores (obtained by averaging the reported scores of two independent pathologists) for independent observer pairs was estimated. The total scores gave higher reliability figures than the final grade both for individual pathologists and double reported scores. The double reported total scores and grade also gave significantly higher reliability figures than the individual scores and grade (average kw=0.65 and 0.78 for the individual and double reported total scores, respectively; 0.61 and 0.66 for the individual and double reported grades).Therefore, use of total scores in addition to grade as well as double reporting of the same significantly increases the interobserver reliability of breast cancer grading.