Down-regulation of the metastasis suppressor protein KAI1/CD82 correlates with occurrence of metastasis, prognosis and presence of HPV DNA in human penile squamous cell carcinoma.

In penile squamous cell carcinoma (PSCC), the outcome largely depends on early detection and resection of inguinal lymph node metastases. We investigated the role of metastasis suppressor protein kang ai 1 (KAI1)/cluster of differentiation 82 (CD82), which is known to be of prognostic significance for a wide variety of cancers. Moreover, we analysed the tumours for human papillomavirus (HPV) DNA and loss of heterozygosity at the 11p11.2 locus. Tissue samples of 30 primary PSCCs were investigated immunohistochemically using an anti-KAI1/CD82 polyclonal antibody. The expression was assessed according to the degree of KAI1/CD82-positive tumour cells as positive, decreased or negative. The presence of HPV6/11, HPV16 and HPV18 DNA was analysed by polymerase chain reaction. All patients with decreased or negative expression of KAI1/CD82 in primary lesions had lymph node metastases (p = 0.0002). Patients with positive KAI1/CD82 expression showed a significant better prognosis for survival compared to the other groups (p = 0.0042). Presence of HPV DNA was associated with decreased or negative KAI1/CD82 expression. Lacking or decreased expression of metastasis suppressor gene KAI1/CD82 appears to be a prognostic parameter for the occurrence of lymph node metastases in PSCC. Our study suggests an association of decreased KAI1/CD82 expression with tumour progression, development of metastases and disease-specific death.

Clear cell chondrosarcoma of the larynx: a case report of a rare histologic variant in an uncommon localization.

The authors describe a clear cell chondrosarcoma of the larynx. The clear cell type is a rare variant of chondrosarcoma that only twice has been reported in this localization. The light-microscopic diagnosis of the actual case was confirmed by immunohistochemical results, in particular by positive staining for S-100 protein and collagen type II, and ultrastructural findings. Loss of heterozygosity analysis demonstrated allelic loss at 9p22 and 18q21, but neither in the region of the Rb gene on chromosome 13q nor at the p53 locus on chromosome 17p where allelic loss has already been reported in chondrosarcomas. Furthermore, our molecular genetic investigations revealed a methylation of the cell cycle control gene p16, which is localized on chromosome 9p. This characteristic has been recorded previously only in high-grade chondrosarcomas. Mutations in the exons of p16, alterations of the putative tumor suppressor gene MMAC1/PTEN on chromosome 10q, or an amplification of the cyclin D1 gene (CCND1) on 11q13, which were found to be changed in other studies of chondrosarcomas, could not be demonstrated here.

Multiple chromosomal underrepresentations detected by interphase cytogenetics - possible prognostic markers in head and neck tumors?

Relevant prognostic factors for head and neck squamous cell carcinoma are tumor extension (pT), occurrence of lymph node metastases (pN) and grade of differentiation (G). We tried to correlate these histological characteristics with numerical aberrations of whole chromosomes as demonstrated by fluorescence in situ hybridization techniques (FISH). Therefore, we investigated isolated interphase cells from paraffin sections of squamous cell carcinomas of the head and neck region from 46 patients with centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumor samples showed aneuploidy for most chromosomes analyzed. The main chromosomal abnormality was loss of chromosomal material, predominantly of chromosomes 3 (28%), 6 (20%), 9 (26%), 10 (24%) and 18 (33%). Multiple deletions could be demonstrated more frequently in poorly differentiated carcinomas (88% G3-tumors with more than one deletion in contrast to 66% G2-tumors). The occurrence of multiple deletions may also correlate with progression in lymph node metastasis (66% in pN0-tumors vs. 85% in pN2-tumors), whereas the differences between the stages of primary tumor extension were not so obvious. Despite of a some-what disproportionate distribution of tumors in the different pT- and pN-stages and the rather low number of cases, our results suggest a relationship between the quantity of chromosomal underrepresentation, grade of differentiation and higher lymph node stage. Therefore, they underline the importance of chromosomal deletions as a possible additional prognostic marker in head and neck squamous cell carcinoma.

Differential expression of the subunits of the glucose-6-phosphatase system in the clear cell type of human renal cell carcinoma - no evidence for an overexpression of protein kinase B.

The expression of two components of the glucose-6-phosphatase system, the catalytic subunit (G6PaseC) and the glucose-6-phosphate transporter, was analyzed in the clear cell type of human renal cell carcinoma. The expression of G6PaseC was decreased in tumours compared with non-tumourous tissue of the same patient. The expression of G6PaseT varied with no general trend between tumours and control tissue. The expression of protein kinase B (PKB) was unchanged in the tumours, suggesting that the down-regulation of G6PaseC in clear cells and the maintenance of the transformed phenotype are not predominantly caused by an overexpression of PKB.

First hints for a correlation between amplification of the Int-2 gene and infection with human papillomavirus in head and neck squamous cell carcinomas.

Infection with human papillomavirus (HPV) and alterations in certain genes have frequently been proposed as mechanisms in the pathogenesis of head and neck squamous cell carcinoma (HNSCC). Here, we investigated 47 HNSCC for the presence of HPV and, by fluorescence in situ hybridisation, for amplification of Int-2 and Hst-1 in the search for a possible correlation. The highest frequency of HPV infection was found in hypopharyngeal carcinomas, while amplification of Int-2 or Hst-1 was distributed more equally among the different localisations. Amplification of Int-2 was detectable (7 of 9 cases) in 78% of the HPV-positive carcinomas, whereas no virus infection could be found in the five cases with amplified Hst-1 only. In spite of the rather low number of infected tumour samples, our results suggest a correlation between HPV infection and amplification of Int-2.

Use of interphase cytogenetics in demonstrating specific chromosomal aberrations in solid tumors--new insights in the pathogenesis of malignant melanoma and head and neck squamous cell carcinoma.

The detection of structural and numerical chromosomal aberrations is an important part of the characterization of tumors and genetic diseases. The direct demonstration of DNA sequences in interphase nuclei and metaphases by fluorescence in situ hybridization (FISH) has been termed interphase cytogenetics. It has been proven as a powerful technique to detect specific aberrations in a wide variety of cell types, including paraffin-embedded tissue. Nowadays a standard method in leukemia and lymphoma, interphase cytogenetics contributes mainly to the diagnosis in these tumors and helps to classify soft tissue tumors. Therefore FISH is mandatory for the choice of therapy in these tumors. In contrast to the aforementioned, up to now, the value of FISH in solid tumors is mostly limited to pure research and contributes in this way to our understanding of tumor biology. But with the use of paraffin-embedded tissue and the first results obtained, it seems very likely that a direct correlation between histological classification and cytogenetic characteristics of solid tumors can be achieved in the near future. This information might not only provide insights into tumor biology, but could also contribute to a different tumor classification, a sort of risk estimation, where we might predict the possible biological behavior of solid tumors. This could greatly influence further therapeutic decisions thus establishing the FISH technique as an indisputable part in the diagnosis of solid tumors.

Different numerical chromosomal aberrations detected by FISH in oropharyngeal, hypopharyngeal and laryngeal squamous cell carcinoma.

AIMS: Little information is available about stage- or site-specific chromosomal aberrations in head and neck squamous cell carcinoma (HNSCC). We tried to identify whether different patterns of chromosomal gain or loss in squamous cell carcinomas were associated with different stages or head and neck sites. METHODS AND RESULTS: We investigated isolated interphase cells from paraffin sections of 5 3 squamous cell carcinomas of the head and neck region by fluorescence in situ hybridization techniques. We used centromeric DNA probes for chromosomes 1, 3, 4, 6, 7, 9, 10, 11, 12, 15, 17, 18, X and Y. The majority of tumour samples showed aneuploidy for most chromosomes analysed. We were able to find differences in the chromosomal aberrations between the tumour sites and stages of the HNSCC investigated. The main numerical chromosomal abnormalities were an under-representation of chromosomes 3 (26%), 6 (17%), 9 (26%), 10 (23%) and 18 (32%). The Y chromosome was lost in 53% of male tumours. A loss of chromosomes 3 and 10 was detected mostly in laryngeal SCC (39% and 30%, respectively); the under-representation of chromosome 9 was predominantly seen in oropharyngeal SCC (54%) and a copy number decrease of chromosomes 18 was found in 57% of hypopharyngeal tumours. CONCLUSION: Although the number of tumour samples investigated is rather low, our results suggest that the different tumour sites of HNSCC may also show different patterns of chromosomal changes.

[Mesoblastic nephroma in adulthood]. / Mesoblastisches Nephrom des Erwachsenenalters.

We report a 44-year-old female patient who underwent surgery because of a suspected primary tumor of the renal pelvis in imaging procedures. Histology revealed the diagnosis of mesoblastic nephroma. This tumor represents a special entity of nephroblastoma that rarely occurs in adults. There is no unanimous opinion on the biological behavior of mesoblastic nephroma because the tumor behaves differently. The question of whether nephrectomy is indicated if there are no malignant features is also open. The decision depends on the given case. Nephrectomy can only be avoided if the intraoperative situation allows the tumor to be removed with an adequate distance from healthy tissue. The safety margin is necessary because mesoblastic nephroma shows fingerlike spread into the surrounding tissue.