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Biomedical subjects

K Y Lam

Publications and source records attributed to K Y Lam.

At least 55 records · Page 3Linked to original sources

Characteristics of malignant tumors in young people, with particular emphasis on carcinomas and sarcomas.

The aims of the study are to investigate the characteristic patterns related to different aged subgroups of young Chinese patients with malignant tumors. The subjects were young Chinese patients (defined as age > 1 and < 40 years) who underwent autopsy for malignant tumors in a teaching hospital in Hong Kong from 1970 to 1999. They were divided into four age groups: 1 to 9 years, 10 to 19 years, 20 to 29 years, and 30 to 39 years. The malignant tumors were classified into subgroups according to the pathological classification. The clinicopathologic features of patients with carcinomas and sarcomas were reviewed in depth. Four hundred sixty-three (22%) of 2,080 young patients had malignant tumors detected at autopsies. The male-to-female ratio was 1.5. The two most common malignant tumors were malignant lymphoid tumors and carcinomas, accounting for 49.9% and 29.8%, respectively, of all malignant tumors. In children (ages 1-9 years), 78.9% of malignant tumors found were malignant lymphoid tumors and neuroendocrine tumors. In teenagers (ages 10-19 years), malignant lymphoid tumors were the most important group of malignant tumor, accounting for 69% of malignant tumors in this age group. Carcinomas and malignant lymphoid tumors were seen in more than 80% of malignancies in young adults (ages 20-39). Overall, carcinomas and sarcomas were noted in 29.8% and 4.1%, respectively, of young patients with malignant tumors. The common primary sites of carcinomas were liver, stomach, lung, and nasopharynx. Sarcomas were more common in females (11 females, seven males), and rhabdomyosarcoma was the most common sarcoma found. Compared with other malignant tumors, carcinomas were less often diagnosed before death. In conclusion, malignant tumor is a common cause of death in young patients. Different types of malignant tumors were seen in various groups of young patients.

Adolescent↗

Carotid artery aneurysm secondary to cystic medial necrosis.

Carotid artery aneurysm secondary to cystic medial necrosis is a rare clinical entity. We report a 59-year-old Chinese male patient who presented with a pulsatile right neck swelling for 2 months. Partial resection of the aneurysm with primary anastomosis of the internal carotid artery was performed. Histopathological examination of the aneurysmal wall demonstrated cystic degeneration of the media with accumulation of glycosaminoglycan material, consistent with the features of cystic medial necrosis. The pathogenesis of carotid artery aneurysm secondary to cystic medial necrosis is discussed.

Aneurysm↗

Identification of differentially expressed genes in esophageal squamous cell carcinoma (ESCC) by cDNA expression array: overexpression of Fra-1, Neogenin, Id-1, and CDC25B genes in ESCC.

PURPOSE: This study aims to identify differentially expressed genes in esophageal squamous cell carcinoma (ESCC) through the use of a membrane-based cDNA array. EXPERIMENTAL DESIGN: Two newly established human ESCC cell lines (HKESC-1 and HKESC-2) and one corresponding to a morphologically normal, esophageal epithelium tissue specimen, prospectively collected from the HKESC-2-related patient, were screened in parallel using a cDNA expression array containing gene-specific fragments for 588 human genes spotted onto nylon membranes. RESULTS: The results of cDNA expression array showed that 53 genes were up-regulated 2-fold or higher and 8 genes were down-regulated 2-fold or higher in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of a subset of these differentially expressed genes gave results consistent with cDNA array findings. Four of the differentially expressed genes that belong to the categories of oncogenes/tumor suppressor genes (Fra-1 and Neogenin) and cell cycle-related genes (Id-1 and CDC25B) were studied more extensively for their protein expression by immunohistochemistry. The two ESCC cell lines and their corresponding primary tissues, 61 primary ESCC resected specimens and 16 matching, morphologically normal, esophageal epithelium tissues were analyzed. The immunostaining results showed that Fra-1, Neogenin, Id-1, and CDC25B were overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the microarray findings. The results of the clinical specimens showed that the Fra-1 gene was overexpressed in ESCC compared with normal esophageal epithelium in 53 of 61 cases (87%), Neogenin in 57 of 61 cases (93%), Id-1 in 57 of 61 cases (93%), and CDC25B in 48 of 61 cases (79%). Furthermore, the expression of Fra-1, Neogenin, and Id-1 in ESCC correlated with tumor differentiation. CONCLUSIONS: Overall, this study demonstrates that multiple genes are differentially expressed in ESCC and provides the first evidence that oncogenes Fra-1 and Neogenin and cell cycle-related genes Id-1 and CDC25B are overexpressed in ESCC.

Carcinoma, Squamous Cell↗

Profiling of differentially expressed cancer-related genes in esophageal squamous cell carcinoma (ESCC) using human cancer cDNA arrays: overexpression of oncogene MET correlates with tumor differentiation in ESCC.

PURPOSE: To examine the global gene expression of cancer-related genes in esophageal squamous cell carcinoma (ESCC) through the use of Atlas Human Cancer Array membranes printed with 588 well-characterized human genes involved in cancer and tumor biology. EXPERIMENTAL DESIGN: Two human ESCC cell lines (HKESC-1 and HKESC-2) and one morphologically normal esophageal epithelium tissue specimen from the patient of which the HKESC-2 was derived were screened in parallel using cDNA expression arrays. The array results were additionally validated using semiquantitative PCR. The overexpression of oncogene MET was studied more extensively for its protein expression by immunohistochemistry in the two ESCC cell lines and their corresponding primary tissues and 61 primary ESCC resected specimens. Sixteen of these 61 ESCC cases also had available the corresponding morphologically normal esophageal epithelium tissues and were also analyzed for MET expression. The clinicopathological features associated with overexpression of the MET gene were also correlated. RESULTS: The results of cDNA arrays showed that 13 cancer-related genes were up-regulated > or =2-fold (CDC25B, cyclin D1, PCNA, MET, Jagged 2, Integrin alpha3, Integrin alpha6, Integrin beta4, Caveolin-2, Caveolin-1, MMP13, MMP14, and BIGH3) and 5 genes were down-regulated > or =2-fold (CK4, Bad, IGFBP2, CSPCP, and IL-1RA) in both ESCC cell lines at the mRNA level. Semiquantitative RT-PCR analysis of 9 of these differentially expressed genes, including the MET gene, gave results consistent with cDNA array findings. The immunostaining results of the expression of MET gene showed that MET was overexpressed in both ESCC cell lines and their corresponding primary tumors at the protein level, validating the cDNA arrays findings. The results of the clinical specimens showed that the MET gene was overexpressed in ESCC compared with normal esophageal epithelium in 56 of 61 cases (92%). Moreover, the overexpression of MET protein was more often seen in well/moderately differentiated than in poorly differentiated ESCC. CONCLUSIONS: Multiple cancer-related genes are differentially expressed in ESCC, the oncogene MET is overexpressed in ESCC compared with normal esophageal epithelium, and its protein overexpression correlates with tumor differentiation in ESCC.

Aged↗

The pancreatic renin-angiotensin system: does it play a role in endocrine oncology?

The characterization of a local renin-angiotensin system in the pancreas has attracted much attention because of its potential clinical applications. A pancreatic renin-angiotensin system may be present in humans and may interact with islet cells. Nevertheless, our knowledge of the renin-angiotensin system in the human pancreas is still in its infancy, especially in the field of endocrine oncology. Much of our knowledge stems from the study of the pancreas and pancreatic endocrine tumors of rodents. Thus, the direction of future research should be based on in-depth and collaborative efforts between researchers in the various disciplines in order to apply the newly acquired scientific knowledge to the patient.

Adenoma, Islet Cell↗

Establishment and characterization of HKESC-1, a new cancer cell line from human esophageal squamous cell carcinoma.

The establishment of an esophageal cancer cell line can facilitate the search for molecular mechanisms involved in esophageal carcinogenesis. A new human cancer cell line, HKESC-1, was established from a primary moderately-differentiated squamous cell carcinoma of the esophagus from a 47-year-old Hong Kong Chinese man. The pathological characteristics (morphology, immunohistochemical, and electron microscopic studies), the tumorigenecity in nude mice, the cytogenetic features, the DNA ploidy, and telomerase activity of the cell line were investigated. The HKESC-1 cells have been maintained continuously in vitro for more than 16 months and passaged over 96 times. HKESC-1 cells grow as a monolayer, with a doubling time of 46 hours. The HKESC-1 cells are of a squamous epithelial origin, as shown by their immunopositivity with the anti-cytokeratin antibodies and ultrastructural demonstration of tonofilaments and desmosomes. The HKESC-1 cells possess characteristics of malignancy because they are highly tumorigenic in nude mice and have strong telomerase activity. The HKESC-1 cells had an aneuploid DNA content, as demonstrated by flow cytometric analysis. Cytogenetic analysis revealed hyperdiploidy of greater than 50 in 80% of analyzable metaphases. Chromosome gains and losses were common, and loss of the Y chromosome was a consistent numerical aberration. Additionally, many structural chromosomal abnormalities were encountered, with frequent breakpoints at 1p32, 7p22, 7q34, and 20q13. This newly established cell line serves as a useful model for studying the molecular pathogenesis, and testing new therapeutic reagents for esophageal squamous cell carcinoma.

Animals↗

Coinfection of multiple strains of Epstein-Barr virus in immunocompetent normal individuals: reassessment of the viral carrier state.

This study reassesses the occurrence of Epstein-Barr virus (EBV) diversity and coinfection versus dominance of a single viral strain within immunocompetent normal carriers. Polymerase chain reaction analysis of several different polymorphic loci of the EBV genome was performed on collections of peripheral blood mononuclear cells and multiple lymphoid and epithelial tissues of the same individuals. Autopsy specimens from 15 individuals who died of causes unrelated to EBV infection served as normal viral carriers. Unexpectedly, coinfection of multiple distinct strains of EBV of the same type (usually type 1) and less frequently of both types 1 and 2 was found to be very high within individual viral carriers. These data indicate that coinfection with multiple EBV strains is much more prevalent in normal carriers than previously appreciated, which in turn has direct implications on EBV persistence, host-viral interaction and pathogenesis.

Carrier State↗

Adrenal pheochromocytoma remains a frequently overlooked diagnosis.

BACKGROUND: Adrenal pheochromocytoma is potentially lethal if undetected and is associated with long-term morbidity. METHODS: Records of patients (11 men, 18 women) with confirmed pheochromocytoma were studied with respect to clinicopathological features and outcome. RESULTS: Pheochromocytoma was diagnosed in 4 of 8,486 (0.05%) autopsies and accounted for 3 of the 4 immediate causes of death. Operative mortality occurred in 1 patient with undiagnosed tumor. Hypertensive-related complications occurred in 6 patients before diagnosis. Malignancy was documented in 7 patients with distant metastases (n = 4) or locally invasive tumors (n = 3). During a median follow-up of 4 years, 23 patients are alive and free of disease (79%). Four of the 6 patients (67%) who died had distant metastases compared with 2 of 23 patients (9%) without distant metastases (P = 0.04). Persistent hypertension and diabetes requiring treatment were present in 8 (35%) and 4 (17%) of 23 patients respectively. CONCLUSIONS: Fatal complications preceded diagnosis in a significant proportion of patients with pheochromocytoma. The presence of distant metastases was associated with poor survival.

Adolescent↗

A comparison of the prognostic significance of tumor diameter, length, width, thickness, area, volume, and clinicopathological features of oral tongue carcinoma.

BACKGROUND: The present study aims at evaluation of the prognostic value of tumor size including diameter, length, thickness, width, area, and volume in the prediction of nodal metastasis, local recurrence, and survival of oral tongue carcinoma. The results will have important implications for the management of patients. METHODS: Eighty-five glossectomy specimens of oral tongue carcinoma were serially sectioned in 3 mm thickness for the tumor size evaluation with computer image analyzer. RESULTS: Among all the tumor size parameters being evaluated, tumor thickness was the only significant factor for the prediction of local recurrence, nodal metastasis, and survival. With the use of 3 mm and 9 mm division, tumor of up to 3 mm thickness has 10% nodal metastasis, 0% local recurrence, and 100% 5-year actuarial disease-free survival; tumor thickness of more than 3 mm and up to 9 mm has 50% nodal metastasis, 11% local recurrence, and 77% 5-year actuarial disease free survival; tumor of more than 9 mm has 65% nodal metastasis, 26% local recurrence, and 60% 5-year actuarial disease-free survival. CONCLUSIONS: Tumor thickness should be considered in the management of patients with oral tongue carcinoma.

Adolescent↗

Microsatellite alterations in squamous cell carcinoma of the head and neck - clustering of loss of heterozygosity in a distinct subset.

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in the carcinogenesis of many cancers, including squamous cell carcinoma of head and neck (SCCHN). However, microsatellite alterations have not been documented in SCCHN from Chinese patients. We investigated the frequency and clinical significance of LOH and MSI in 30 SCCHN from Hong Kong Chinese using polymerase chain reaction on 17 microsatellite markers on chromosomes 3p, 4q, 7q, 9p, 17p and 18q. LOH was present in nine tumours (30%) and MSI in four (13%). The incidence of LOH (7/13; 53.8%) in hypopharyngeal-laryngeal cancers was significantly higher than that (2/17; 11.8%) in the oral cancers (P=0.020). LOH was more often detected at the loci on chromosomes 7 and 9. Patients with tumours having LOH had slightly poorer outcome compared with those without, although the differences did not reach statistical significance. Our data show that the incidence of microsatellite alterations in SCCHN from Hong Kong Chinese is low. However, LOH may be one of the genetic mechanisms in the carcinogenesis of a subset of SCCHN (hypopharyngeal-laryngeal cancers).

Adolescent↗

Cyclin D1 expression in oral squamous cell carcinomas: clinicopathological relevance and correlation with p53 expression.

The aim of the present study is to study the relationship between cyclin D1 and the clinicopathological features of oral squamous cell carcinomas. The cyclin D1 and p53 expression in oral squamous cell carcinomas from 56 patients (45 men, 11 women) was studied by immunohistochemistry using monoclonal antibodies. The correlation between cyclin D1 and the clinicopathological features of the oral cancers was evaluated. Cyclin D1 expression was found in 63% of oral squamous cell carcinomas; it was often weak but was more frequently positive in high-grade lesions (P=0.019). The expression was positively correlated with p53 expression (P= 0.06). Radiation therapy did not alter the expression of either cyclin D1 or p53 proteins. Expression of these proteins was not related to the age, gender or survival of the patients, or to stages of the tumors. The cyclin D1 expression was more frequently seen in patients with squamous cell carcinomas of oropharynx, palate, floor of mouth and gingiva. To conclude, cyclin D1 was frequently expressed in oral squamous cell carcinomas. This expression was related to the grade of the tumors and was not similar in various regions in the oral cavity, which may indicate the different tumor biology of cancers from these regions.

Adult↗

Insular and anaplastic carcinoma of the thyroid: a 45-year comparative study at a single institution and a review of the significance of p53 and p21.

OBJECTIVE: To analyze the clinicopathologic features of a large cohort of patients with insular or anaplastic carcinomas treated at a single institution. SUMMARY BACKGROUND DATA: Insular and anaplastic carcinomas of the thyroid, although uncommon, have more aggressive clinical behavior than well-differentiated carcinomas of the thyroid. In the literature, the incidence and features of these carcinomas have not been fully characterized. METHODS: The authors reclassified 740 primary thyroid carcinomas diagnosed and treated between January 1, 1954, and December 30, 1998, to select those with features that met the histologic criteria of insular or anaplastic carcinoma. The clinicopathologic features of these carcinomas were studied and compared. The expression of p53 and p21 in these tumors was analyzed by immunohistochemistry. RESULTS: Twenty-two patients (5 men, 17 women) with insular carcinoma and 38 patients (7 men, 31 women) with anaplastic carcinoma were found. Patients with insular carcinomas were younger (mean age 45 vs. 70 years) and had smaller tumors than those with anaplastic carcinomas (mean diameter 5 vs. 8 cm). Insular carcinomas were commonly mislabeled as other histologic subtypes, whereas anaplastic carcinomas might be overdiagnosed on pathologic examination. A history of longstanding goiter (>10 years) was noted in 27% of patients with insular carcinoma and 24% of patients with anaplastic carcinomas. Concomitant well-differentiated carcinomas of the thyroid were noted in 59% of patients with insular carcinoma and 39% of patients with anaplastic carcinoma. In anaplastic carcinomas, 13% of patients had concomitant insular carcinoma. Calcification or bone was noted in the stroma of 23% of patients with insular carcinomas and 47% of those with anaplastic carcinomas. The 10-year survival rates for patients with insular carcinoma and anaplastic carcinoma were 42% and 3%, respectively. Distant metastases were seen in 32% of patients with insular carcinoma and in 47% of patients with anaplastic carcinomas. In both types of carcinomas, metastatic tumors were often seen in bone and lung. Distant metastases were noted in a variety of organs in anaplastic carcinomas. In insular carcinoma, neither p53 nor p21 expression was present. In anaplastic carcinoma, p53 and p21 expression was identified in 69% and 3%, respectively. Concomitant expression of p53 and p21 was noted in one tumor. CONCLUSIONS: Insular carcinoma and anaplastic carcinoma had distinctive clinicopathologic features, and recognition of these histologic variants is important for better management of these tumors in the future. p53 overexpression might have a role in dedifferentiation from insular carcinoma to anaplastic carcinoma.

Adolescent↗

Odontogenic keratocysts: a clinicopathological study in Hong Kong Chinese.

OBJECTIVE: To analyze the clinicopathological features of odontogenic keratocysts in Chinese patients. STUDY DESIGN: Retrospective analysis. METHODS: The clinical records and pathological features of odontogenic keratocysts from 69 ethnic Hong Kong Chinese patients (40 male and 29 female patients) were reviewed. RESULTS: The male-to-female ratio was 1.4:1; patient age ranged from 6 to 69 years with a modal peak in the third decade (mean age, 28 y; median age, 23 y). The preoperative diagnosis was correct in 78% of the cases and the most common misdiagnosis was dentigerous cyst. Sixty-two percent of the cysts were found in the mandible, and 38% in the maxilla. Multiple cysts occurred in 9% (including three cases of basal cell nevus syndrome). Histologically, 82.6%, 5.8%, and 11.6% of the cysts were parakeratinized, orthokeratinized, and mixed types, respectively. Patients with multiple cysts all showed parakeratinization. The majority (80%) of the cysts were lined by epithelia with a thickness of five to eight cells. Surface corrugation, subepithelial split, suprabasal split, satellite microcysts, epithelial islands, significant inflammation, hyaline bodies, and dystrophic calcification were present in 10%, 81%, 25%, 38%, 42%, 46%, 7%, and 10% of cysts, respectively. The overall recurrence rate was 240%, with a median time for first recurrence of 19 months (range, 1 mo-22 y). Cysts showing orthokeratinization or mixed types of keratinization recurred less often than parakeratinized cysts. Recurrence had the same type of keratinization as the initial cyst. CONCLUSIONS: Pathological examination of keratocysts is important, because keratocysts have different clinicopathological features and carry a risk for clinical misdiagnosis.

Adolescent↗

Telomerase activity in pancreatic endocrine tumours: a potential marker for malignancy.

AIMS: Telomerase activation is known to be a common event in human cancer and may be a useful marker for malignancy. In general, the histological features of pancreatic endocrine tumours cannot be used to determine their malignant potential. The aim of this study was to investigate the role of testing telomerase activity in pancreatic endocrine tumours. METHODS: Prospectively collected fresh frozen tissue specimens from 10 patients with pancreatic endocrine tumours (nine insulinomas, one adrenocorticotrophin producing pancreatic endocrine tumour) were examined by a highly sensitive polymerase chain reaction (PCR) based telomerase repeat protocol (TRAP). RESULTS: Of the 10 pancreatic endocrine tumours, three had telomerase activity. The positive cases included two frankly malignant tumours with liver metastases and one pancreatic endocrine tumour occurring in the setting of multiple endocrine neoplasia type 1. The latter had an infiltrative border. Vascular and perineural tumour infiltration was noted. In the two malignant pancreatic endocrine tumours with liver metastases, telomerase activity was noted in the tumour and the adjacent morphologically non-neoplastic pancreas. CONCLUSION: To our knowledge, this is the first report of the role of telomerase activity in pancreatic endocrine tumours. Telomerase activity might be useful for distinguishing between benign and malignant pancreatic endocrine tumours.

Adult↗