Biomedical subjects

Albert Roessner

Publications and source records attributed to Albert Roessner.

96 records · Page 6Linked to original sources

PubMed2002

Homozygous proline at codon 72 of p53 as a potential risk factor favoring the development of undifferentiated thyroid carcinoma.

The p53 tumor suppressor gene is altered in human cancer. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). No data exist about the association of a distinct codon 72 variant with the histological subtypes of thyroid carcinoma. We developed a new one-step real-time PCR assay on the LightCycler to detect codon 72 polymorphism in the p53 gene. We studied 21 papillary, 18 follicular and 22 anaplastic thyroid carcinomas and compared them with 15 adenomas and 36 normal thyroid tissues (controls); moreover, we compared the cases for histological, clinical and demographic variables and genotype prevalence. In controls, the frequency of the three genotypes Arg/Arg, Arg/Pro, and Pro/Pro was 41.7, 50.0 and 8.3%, respectively. The homozygous proline was not found in benign thyroid adenomas and differentiated thyroid carcinomas. In contrast, all undifferentiated thyroid carcinomas (100%) had the homozygous proline phenotype. The frequency of the two other genotypes Arg/Arg and Arg/Pro was 66.7% and 33.3% in adenomas, 81.0% and 19.0% in papillary thyroid carcinomas, and 83.3% and 16.7% in follicular thyroid carcinomas, respectively. Comparing the genotypes with tumor stage, no correlation was found. However, lymph node and distant metastases status showed a statistically significant prevalence for the homozygous phenotypes Arg/Arg and Pro/Pro. There was no association between a special genotype and age and sex. We conclude that homozygous proline is a potential risk factor favoring the development of an undifferentiated thyroid carcinoma, and that the homozygous phenotypes at codon 72 of p53 are associated with a poorer prognosis of thyroid carcinoma.

Adult↗

PubMed2001

Immunohistochemical and molecular analysis of p53, RB, and PTEN in malignant peripheral nerve sheath tumors.

The molecular basis of both sporadic and neurofibromatosis type 1 (NF1)-associated malignant peripheral nerve sheath tumors (MPNSTs) is yet largely undetermined. Therefore, we analyzed a series of 12 MPNSTs - including two cases which arose in the setting of NF1 - for molecular alterations in the p53, retinoblastoma ( Rb), and PTEN tumor suppressor genes. Furthermore, the immunohistochemical expression of p53, RB, and PTEN protein was examined in these tumors. One mutation (8%), an A to T transversion leading to an amino acid exchange, was found in exon 5 of the p53 gene in a sporadic MPNST. In two other sporadic tumors (20%), loss of heterozygosity (LOH) of the p53 gene occurred. Nuclear overexpression of p53 protein was observed in ten tumors (83%). Loss of RB protein expression was seen in two MPNSTs (17%), and LOH of the Rb gene was detected in four tumors (44%), including the two NF1-associated MPNSTs, one of them showing concomitant loss of RB protein expression. No mutation in the PTEN gene was detected, and cytoplasmic immunoreactivity for the PTEN protein was maintained in eight MPNSTs (67%). We suggest that alterations in the p53 and RB pathway, both are essential in controlling the cell-cycle progression, are critical points in the tumorigenesis of sporadic and NF1-associated MPNSTs, whereas the PTEN gene seems to play no significant role in this process.

Adult↗

PubMed2001

Amyloidosis of the breast.

We report on three cases of amyloidosis of the breast, two of which coincided with breast cancer. Patient no. 1, a 60-year-old woman, presented with two mass lesions measuring 2 cm in diameter, one in each breast. Histologically, a tubulo-lobular carcinoma was found in the left breast accompanied by vascular, interstitial, and periductal amyloid deposits; the lesion in the right breast consisted of amyloid deposits only. Patient no. 2, an 86-year-old woman, presented with an ulcerated breast tumor measuring 5 cm in diameter on the left side. A poorly differentiated invasive ductal carcinoma was found in the mastectomy specimen, and it coincided with interstitial and vascular amyloid deposits. In both patients, tumor cells had invaded the amyloid deposits. Patient no. 3, a 73-year-old woman, presented with a mass measuring 5 x 3 x 3 cm in her left breast. Fibrocystic changes, as well as interstitial and periductal amyloid deposits, were found histologically. In each case electron microscopy showed rigid, non-branching fibrils of indefinite length and measuring 10-12 nm in diameter; these were consistent with amyloid fibrils. Clinical data, immunohistochemistry, and/or amino acid sequencing of the fibril proteins extracted from formalin-fixed and paraffin-embedded tissue specimens provided evidence that the amyloid deposits were of immunoglobulin light chain origin in all three cases. A review of the literature revealed that kappa-light chain has been described more frequently than lambda-light chain in the breast and that there are no specific clinical or radiological symptoms of amyloidosis affecting the breast; a diagnosis can be achieved only by histology.

Aged↗

PubMed2001

Evaluation of arthroscopic articular cartilage biopsy for osteoarthritis of the knee.

PURPOSE: Arthroscopic evaluation of the articular surface by visualization and palpation has proved to be unreliable; therefore, we investigated arthroscopically procured biopsy specimens and conventional sections by using the same histopathomorphologic techniques and compared the results for possible differences. METHODS: Cartilage biopsy specimens of 1.7 mm in diameter and conventional cartilage sections (pieces of 8 x 2 mm) were removed from the lateral femoral condyle of 53 osteoarthritis patients undergoing total knee arthroplasty. Biopsies and conventional sections were evaluated histologically by using Mankin's grading system and immunohistochemically by assessing the immunoreactivity of the chondrocytes to MMP-1 and MMP-3. RESULTS: The comparison between the biopsies and conventional sections revealed that there were no differences between these forms of obtaining specimens. Moreover, the expression of MMP-1 and MMP-3 in biopsy specimens showed a strong correlation with that in conventional sections. CONCLUSIONS: We conclude that in small biopsy specimens taken (e.g., during arthoscopy), the histological grading of osteoarthritis severity and the evaluation of MMP expression yield results similar to those obtained in conventional sections.

Journal Article↗

PubMedDate not supplied

Selective loss of codon 72 proline p53 and frequent mutational inactivation of the retained arginine allele in colorectal cancer.

According to recent reports, some cancer types exhibit nonrandom allele loss at codon 72 in exon 4 of the p53 gene [coding for proline (72Pro) or arginine (72Arg)]. To clarify this phenomenon for colorectal cancer and to find out if this preferential loss might have any functional significance, p53 loss of heterozygosity (LOH) and p53 mutations were investigated in a group of 61 colorectal cancers and 28 liver metastases, and were correlated with clinicopathologic factors. A comparison of a patient's blood codon 72 status with a healthy control group did not reveal an enhanced risk of developing colorectal tumors for one of the two isoforms. p53-LOH and p53 mutations were found in 62.2% and 39.4% of primary tumors, respectively, and in 57.9% and 25% of hepatic metastases, respectively. In 14 heterozygous cases showing exon 4-LOH, only the 72Pro allele was lost and the retained 72Arg was preferentially mutated. In general, p53 mutations were significantly associated with the 72Arg tumor status (P < .001). Distal tumors showed allelic losses of the p53 gene more commonly than proximal tumors (P = .054). The prevalence of 72Arg increased in frequency with higher Dukes stage (P = .056). We suggest that either the preferential loss of 72Pro or the mutation of the 72Arg in colorectal cancer and hepatic metastases is associated with malignant potential and might reflect carcinogenic exposure, particularly in the distal part of the large intestines.

Adult↗

PubMedDate not supplied

Maspin in thyroid cancer: its relationship with p53 and clinical outcome.

The serine protease inhibitor maspin has been reported to inhibit invasiveness and motility of tumor cells. Additionally, a p53-dependent regulatory pathway of maspin in human cancer has been indicated. In a pre-study we were able to detect maspin protein in papillary thyroid carcinomas (PTC), whereas normal (tumor-free) thyroid tissue, follicular adenomas, follicular carcinomas, poorly differentiated carcinomas and undifferentiated carcinomas of the thyroid were maspin-negative. The first aim of our study was to determine the prognostic value of maspin protein expression for the recurrence-free and overall survival of PTC patients undergoing radical thyroidectomy and postoperative irradiation. Secondly, maspin expression was correlated to p53 protein expression in order to gain additional information on a possible regulatory influence of the wild-type p53 protein on maspin. An immunohistochemical approach study was performed on 68 tumor specimens. Maspin protein expression was detectable in 48 of 68 patients (71%; M+). After a median follow-up of 81 (26-117) months the median recurrence-free survival was 60 (28-117) months for M+ and 42 (11-108) months for M- (p=0.03). After 110 months 83% of patients had recurrence-free disease in M+, whereas in M- only 40% of patients were recurrence-free. The median long-term survival was 81 (42-108) months for M+ and 55 (21-99) months for M- (p=0.03). After 5 years, M+ and M- patients had a total survival of 98 and 80%, and after 9 years 90 and 60%, respectively. Mutant-type p53 expression was detectable in 17 of 68 PTC (25%). Mt p53 was positive in 1 of 47 M+ (2%) compared with 16 of 20 M- (80%, p<0.01). This study indicates that maspin protein possibly functions as a clinically relevant inhibitor of tumor progression, preventing local invasiveness and further systemic progression of papillary thyroid carcinomas. Our data hint of a p53-dependent regulatory pathway of the maspin protein in human cancer.

Adult↗