A renewed insight into Barrett's esophagus: comparative histopathological analysis of esophageal columnar metaplasia.

Specialized intestinal metaplasia (SIM) is considered as a premalignant condition of the esophagus, but other types of esophageal metaplasia are commonly neglected. A standardized histopathological analysis was focused not only on SIM but also on the presence of metaplastic processes typical of additional glands. A morphological study using standardized histopathological tests was carried out between 2004 and 2007, with biopsies taken from esophageal mucosa of 826 consecutive patients. Mean age and male : female ratio of patients were 55.6 ± 14.7 and 1.1 : 1, respectively. Only 4.1% (n = 34) of all cases proved to have SIM. The remainder of the cases (n = 615; 74.4%) contained cardiac-fundic mucosa without SIM. Some samples exhibited superficial mucous glands, pancreatic acinar metaplasia (PAM), and ciliated metaplasia accounting for 24% (n = 198), 14.9% (n = 123), and 0.2% (n = 2), respectively. SIM was colocalized with superficial mucous glands (103/198 superficial mucous gland cases; P < 0.001). Low-grade dysplasia (n = 51; 6.2%) and high-grade dysplasia (n = 9; 1.1%) were found mainly in SIM (37/51; 9/9; P = 0.071) with male preponderance (3 : 1 at low-grade and 2 : 1 at high-grade dysplasia). PAM was found mainly in cases without dysplasia (103 of 123 pancreatic metaplasias; P < 0.001). SIM alone in the esophagus is rare, and its frequent association with cardiac mucosa-type metaplasia testifies to transition of mucinous-goblet cell through pseudogoblet cells. PAM rather indicates absence of dysplasia, but superficial mucous glands predicts that SIM follows dysplasia.

Mapping a tumor suppressor gene to chromosome 2p13 in metanephric adenoma by microsatellite allelotyping.

Twelve metanephric adenomas (MA) were studied for allelic imbalance at chromosomal regions known to be involved in the genetics of papillary renal cell tumors (RCT) and Wilms' tumors as well as for loci on chromosome 2p13-21. DNA was isolated from paraffin slides, and allelic status was established by fluorescently-labeled microsatellite markers. No allelic changes were seen in the Wilms' tumor gene region at chromosome 11p13 and in the papillary RCT gene region at chromosome 17q21.32. We delineated a tumor suppressor gene region of approximately 8-centimorgan genetic distance between loci D2S2153 and D2S380 on chromosome 2p13. Allelic changes at this region occurred in 56% of informative cases. Our results provide molecular evidence that MA is a genetic entity, and it can be differentiated from both Wilms' tumor and papillary renal cell adenoma.

Allelic loss at 10q23.3 but lack of mutation of PTEN/MMAC1 in chromophobe renal cell carcinoma.

Chromophobe renal cell carcinoma (RCC) is characterized by loss of multiple chromosomes including chromosome 10. This study was undertaken to determine the LOH at the PTEN/MMAC1 locus (chromosome band 10q23.3) and to search for gene mutations in 15 chromophobe, 50 conventional, and 10 papillary RCCs as well as in 10 renal oncocytomas. Loss of heterozygosity (LOH) wa seen at all informative loci in all chromophobe RCCs and in two conventional RCCs. We did not find mutations by analyzing exon 1 to 9 of the PTEN/MMAC1 gene using the PCR-SSCP technique in tumors with LOH at 10q23.3.

Prognostic histological and immune markers of renal cell carcinoma.

Recent development on the fields of molecular genetics and immunology of human renal cell carcinoma (RCC) have resulted in more successful treatment of advanced and metastatic RCCs. Re-evaluation of the prognostic/predictive data aim the initial tumor staging of RCC patients to achieve better patient selection for immune and gene therapy. 125 RCC patients diagnosed according to the Heidelberg histological classification, graded, Robson staged, immune treated (Interferon-a a+ Vinblastine or Broncho-Waxom/Decaris) were followed-up clinically for 36 months. Tumor immunity markers by immunohistochemistry of tumor infiltrating lymphocytes (TIL) were detected by immunoperoxidase methods using monoclonal antibodies. Tumoral immune complexes (TIC) were visualized by fluorescent polyclonal antibodies. Histologically oncocytomas defined a better (p<0.02) and sarcomatous RCCs a worse (p<0.01) follow-up prognosis. Basically, the metastatic status (related with the stage and grade) determined the clinical outcome (p<0.00002) of the RCC patients. Tumoral immune complexes (TIC) were weak positive, while tumor infiltrating lymphocytes (TIL) weak negative predictors of the succes of Broncho-Waxom/Decaris immune therapy. Molecular genetic based histological classification, grade, stage and metastatic status parameters together with some tumor immunity parameters (TIL, TIC) can predict the success of immunotherapy of RCC patients.

Tibia metastasis without prostate specific antigen (PSA) increase following radical vesiculo-prostatectomy.

OBJECTIVES: PSA is regarded as the best method in the follow-up of prostate carcinoma. After radical vesiculo-prostatectomy the prostate carcinoma seldom recurs at zero or nearly zero PSA levels. METHODS: The authors have used PSA since 1989 and they have found only one case where metastasis in the tibia came without an increase in PSA levels. RESULTS: Tibia metastasis showed lower tissue activity of PSA than did the primary tumor in the prostate. The authors think this explains the zero PSA level when the metastasis developed. CONCLUSIONS: The authors think based on their case that PSA free progression prostate cacncers may cases where the metastases do not produce PSA.

[Paraneoplastic nephropathy associated with adult renal carcinoma (immunologic and clinicopathologic study)]. / A felnöttkori vesecarcinomát kísérö paraneoplasiás nephropathia (immunológiai és klinikopatológiai tanulmány).

Rare "paraneoplastic nephropathies" are associated with a wide variety of human tumors. Little is known about the pathogenetical background. To our knowledge no systematic study about the association of potentially "immunogenic" renal cell cancer (RCC) and "paraneoplastic nephropathy" has been published so far. An immunohistochemical analysis of native kidneys and a nephrological follow up of 60 patients with renal cell cancer (RCC) treated at the Department of Urology, medical University, Pécs (Hungary) between 1993-1998 has been performed. Cellular and humoral immunity was analysed by immunohistochemistry. Clinical/laboratory parameters of the patients with tumor associated nephropathy were pre- and postoperatively registered. Eleven IgA-nephropathy (IgA-NP) and 5 focal segmental glomerulosclerosis (FSGS), manifested in preoperative clinical signs in 11 out of 16 cases were found. Clinical symptoms disappeared in 6 out of 8 IgA-NP patients by tumor nephrectomy in a follow up of 38.7 (18-51) months. Eleven out of 16 tumors were stained with the identical anti human immunoglobulin (IgA or IgM) present in the glomerular immune complexes. The RCC-associated VHL (von Hippel-Lindau) protein was detectable in 3 out of 8 IgA-NP patients as an antigen component of their nephritogenic immune complexes. Tumor infiltrating lymphocytes (TIL) considered as a local sign of cellular tumor immunity were more frequently present in tumors associated with nephropathy than without it (69% vs 25%). Pathogenetic correlation between the tumor immunity in renal cell carcinoma and "paraneoplastic IgA-nephropathy" has been demonstrated in some of the cases. Tumor nephrectomy excluding the need of post-operative single kidney biopsies should be a safe tool in the differential diagnosis of tumor-associated nephrological conditions.

[Parvovirus B19 infection in hydrops fetalis]. / Parvovírus B19-infekció foetalis hydropsban.

In a retrospective study from 210 foetal autopsies carried out in a period between 1992 and 1999 fifteen hydropic foetuses were found. The cause of the hydrops was shown to be Rh incompatibility in one case only. The cause of hydrops was not discernible in one case. In the others pathological examination clarified the cause and pathomechanism of non-immune hydrops. One isolated cystic hygroma, one monochorionic twin pregnancy with twin to twin transfusion, one case of sacrococcygeal teratoma and 4 cases of congenital heart diseases were reported. Postmortem interphase cytogenetic examination showed X0 monosomy in 2 cases. In further 4 foetuses pathognomic viral inclusions in the proerythroblasts raised the probability of parvovirus B19 infection what was confirmed by immunohistochemistry and electronmicroscopic examination. The occurrence of the parvovirus B19 associated cases of foetal hydrops was shown to be higher (4/15) in this series than in the literature. The accumulation of cases in 1998 is suggestive of an outbreak. The prenatal diagnostic implications and the attempts on further management are also discussed.

High density deletion mapping of bladder cancer localizes the putative tumor suppressor gene between loci D8S504 and D8S264 at chromosome 8p23.3.

Deletion of chromosome 8p is associated with the progression of bladder cancer. To identify the putative tumor suppressor gene locus we have analyzed 145 bladder cancers with 12 microsatellite markers for allelic changes at the chromosome 8p23.3 region. We mapped the smallest overlapping deletion to approximately 0.7 cM genetic distance between loci D8S504 and D8S264. Allelic changes at this region occurred in 75 (52%) of the 145 tumors. We found a significant correlation between alterations at chromosome 8p23.3 and the tumor grade. The correlation between genetic changes and tumor stage reflected the distribution of tumors of different grades in each pathologic stage.

Renal cell carcinoma and paraneoplastic IgA nephropathy.

Paraneoplastic nephropathy is rarely associated with human tumors. Little is known about the pathogenetic background of this relationship. To our knowledge, no conclusive study of the association of potentially 'immunogenic' renal cell carcinoma (RCC) and paraneoplastic nephropathy has been published. For this reason, we performed an immunohistochemical analysis of native resected kidneys of 60 patients with RCC, paying special attention to their pre- and postoperative records. Sixteen (27%) of the 60 tumor patients had immune complex nephropathy (11 IgA nephropathy [IgA NP] and 5 focal segmental glomerulosclerosis [FSGS]). Preoperative proteinuria and/or hematuria observed in 11 of 16 cases disappeared in 6 IgA NP patients within a 2- to 3-month follow-up after nephrectomy. Eleven of 16 tumors stained with the anti human immunoglobulin (IgA or IgM) of the same isotype as that present in glomerular immune complexes. In 3 IgA NP patients RCC-associated von Hippel-Lindau (VHL) protein and IgA staining were found simultaneously in the tumor and glomeruli, with the clinical and laboratory findings disappearing after nephrectomy. Immune injury of the glomeruli due to a tumor-induced antigen-antibody response was demonstrated in these 3 IgA NP patients.