Role of microsatellites instability in carcinogenesis of postcricoid carcinoma on top of plummer-vinson syndrome.

To develop a molecular pattern that might help in understanding carcinogenesis of postcricoid carcinoma (PCC) on top of Plummer-Vinson syndrome (PVS) in a prospective controlled study. Twenty-four patients with PVS were diagnosed and followed up over a 4 year period, during which eight of them showed malignant change to PCC. Twenty volunteers free of neoplastic diseases were included as a control group. In the two groups, DNA extraction from mononuclear peripheral blood cells, and analysis of loss of heterozygosity (LOH) and microsatellite instability (MSI) using six paired simple tandem repeats (STRs) primers were done. The molecular weight of each STRs locus was scored and statistical correlations were performed. LOH occurred in 55.6 and 72.9% of PVS and PCC cases compared to 25% of control group. At loci D17S695, D9S753 and D9S171, LOH occurred in 54.2, 66.7, and 70.8% of PVS cases; and in 62.5% of PCC cases for each locus compared to 15, 25 and 45% of control cases. D3S1286 and CFS1-R displayed the highest frequency of LOH in PCC (100% for each) while recorded in 58.3 and 33.3% in PVS compared to 30 and 0% in control cases. Certain genetic events tend to occur as early and late events in malignant change of PVS to PCC. Detection of these events may help in understanding carcinogenesis and in early detection of malignancy. CFS1-R is the most informative marker of tumor progression.

The role of genetic susceptibility in head and neck squamous cell carcinoma.

Our research is an additional genetic study to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying loss of heterozygosity (LOH) and microsatellite instability (MSI) in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. Patients with HNSCC from various parts of the world may have unique genotypes and this is the first genetic study of HNSCC in Sohag 500 KM to the south of Cairo. We performed a prospective study of 41 patients with precancerous and 79 patients with cancerous laryngeal, esophageal, nasopharyngeal, nasal and oral lesions, and 50 controls (The control patients were cases admitted for ear surgery or simple nasal surgery, from whom we took biopsy from mucosal lining of nasopharynx). The present study included 170 individuals who were admitted to the Ear, Nose and Throat department, Sohag University Hospital, Sohag, in Egypt in the period between April 2001 and March 2003. Samples which were taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. We investigated LOH and MSI by using six microsatellite markers located at chromosomes 3, 5, 9, and 17. The markers used were D3S1286, D9S171, D9S753, D17S654, D17S695, and CFS1-R. LOH was in all premalignant and malignant lesions at 5q33.3-q34 and 13% of Controls. LOH at 17p21 was absent in all premalignant lesions and was found in 53% of malignant lesions and 12.4% of Controls. In premalignant lesions, LOH was at 3pter-3p24.2 (73% of cases), at 9p21 (46%), at 9q21.1-22.3 (37%), and at 17p13 (37%). These percents increased in malignant lesions to 87, 80, 67, and 63%, respectively. They were 14, 19.4, 17, and 19% in controls. Examination of LOH could improve diagnosis, adds additional confidence, in HNSCC by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and LOH at 3p/9p seems to be of particular value for early detection and definition of progression risk. If there are high percent of LOH at these chromosomes, active intervention should be done (chemoprevention and regular follow up head and neck examination for very early detection and management).

The role of chromosomal aberrations in premalignant and malignant lesions in head and neck squamous cell carcinoma.

The objectives of this study are to uncover the molecular mechanisms involved in head and neck squamous cell carcinoma (HNSCC) pathogenesis by studying the chromosomal aberrations in both premalignant and malignant patients and to highlight the genotype of HNSCC in Upper Egypt. From March 2001 to December 2003, prospective study was conducted in 41 patients with precancerous, 79 patients with cancerous laryngeal, oesophageal, nasopharyngeal, nasal, and oral lesions and 50 controls in ENT department, Sohag Faculty of Medicine, Sohag, Egypt. Samples taken by punch biopsy were frozen and stored at -80 degrees C and were subjected to histopathological examination. Metaphase cells were digitally imaged and karyotyped. Karyotypes have been analysed via anatomical image capture and compared with standard human chromosome ideograms. In precancerous lesions, there were 41% 3p loss, 51% 3q gain, 29% 8q gain, and 22% 11q13 gain. In malignant lesions, there were 63% 3p13-p24 loss, 59.5% 5q12-23 loss, 49.5% 8p22-p23 loss, 45.5% 9p21-p24 loss, 40.5% 18q22-q23 loss, 66% 3q gain, 39% 8q gain, and 16% 11q13 gain. In conclusion, early diagnosis of HNSCC can be achieved by DNA extraction from suspicious lesions in high-risk groups (smokers and alcoholics) and examination of chromosomal aberrations of 3p, 3q, 8q, and 11q13. If there are high percent of chromosomal aberrations in these chromosomes, active intervention should be done (chemoprevention and regular follow-up of head and neck examination for very early detection and management).

The flow cytometric analysis of premalignant and malignant lesions in head and neck squamous cell carcinoma.

We attempted to identify the molecular mechanisms involved in Head and Neck Squamous Cell Carcinoma (HNSCC) pathogenesis by measuring the nuclear DNA content (ploidy) in premalignant (potentially malignant) and malignant patients as compared to normal controls, and to determine whether DNA ploidy could be used to predict the clinical outcome. From March 2001 to December 2003, the analysis was carried out in a set of 41 patients with premalignant lesions and 79 suffering from squamous cell carcinoma of laryngeal, oesophageal, nasopharyngeal, nasal and oral lesions and 50 controls. Representative samples were taken by punch biopsy and processed using standard formol-paraffin technique for histopathological examination. Fifty micrometer thick sections of paraffin-embedded tissues were analyzed to detect the DNA content by image cytometry. Of the potentially malignant patients, 46% had diploid lesions, 37% had tetraploid lesions and 17% had aneuploid lesions. While of the patients with cancer, 90% had aneuploid lesions, 10% had diploid lesions and none had tetraploid lesions. DNA diploidy tended to occur earlier in the progression from premalignant to malignant lesions and this helps us early detection of HNSCC by DNA from lesions in high risk groups and examination of its ploidy. Knowledge of tumor cell ploidy by DNA image cytometry may facilitate the evaluation of malignant and premalignant lesions in HNSCC. The present findings are promising to supplement clinical and histopathological parameters in evaluating prognosis and to demonstrate methods that are readily applicable for routine diagnostic work.