title: Molecular Pathology of Oesophageal Tumours
Creators: name: Lam, Alfred
Publisher: name: Griffith University
Year: 2006
Subjects: subject: Oesophageal tumours
subject: Hong Kong Chinese
subject: squamous cell carcinoma
subject: mucoepidermoid carcinoma
subject: adenosquamous carcinoma
subject: basaloid squamous carcinoma
subject: sarcomatoid carcinoma
subject: glomerulonephritis

description: Oesophageal tumours are very common worldwide. This thesis aims to delineate the clinicopathological features and molecular biology of oesophageal tumours in Hong Kong Chinese. Over a 30-year study period, oesophageal tumours were obtained in the pathology files of the Queen Mary Hospital, Hong Kong. The tumours were prevalent in males and had a modal peak occurrence in the 7th decade. Patients often presented at an advanced stages. At autopsy, the prevalence of incidental oesophageal cancers and early-stage cancers were low. Many histological subtypes of oesophageal cancers were noted and were different from the Western populations. The most common histological subtype was squamous cell carcinoma, often moderately-differentiated. Besides the classical squamous cell carcinomas, variants like mucoepidermoid carcinoma/adenosquamous carcinoma, basaloid squamous carcinoma and sarcomatoid carcinoma were noted. The prognosis of squamous cell carcinoma with a mucin-secreting component (mucoepidermoid carcinoma and adenosquamous carcinoma) was not significantly different from that of patients with pure squamous cell carcinoma or adenocarcinoma. The glandular component of this group of tumours histochemically differentiated in the direction of oesophageal glands. Basaloid squamous cell carcinoma had distinctive clinicopathological features and its long-term prognosis was no worse than squamous cell carcinoma. Glomerulonephritis could be a para-neoplastic manifestation of basaloid squamous carcinoma of oesophagus. Sarcomatoid carcinomas were also found, and rarely double sarcomatoid carcinomas could be noted in the same patient. The other carcinomas noted in the oesophagus were small cell carcinoma and adenocarcinoma. Oesophageal small cell carcinoma was an aggressive tumour. The high proliferative index correlates with aggressive behaviour and high sensitivity to chemotherapy and radiotherapy. Oesophageal adenocarcinoma was uncommon in Hong Kong. On the other hand, intestinal metaplasia, known to be associated with adenocarcinoma, was prevalent at the gastroesophageal junction in Chinese patients undergoing endoscopy. The non-epithelial tumours in the oesophagus comprised melanoma and mesenchymal tumours. Melanoma of the oesophagus was an aggressive tumour. All patients with the tumour had short survival. Mesenchymal tumours consisted of leiomyoma, undifferentiated stromal tumour and autonomic nerve tumour. Intramural metastasis and multiple tumours were frequently observed in oesophageal cancer. This implies that wide excision with wide margins should be considered for local control of the disease. Pre-operative chemotherapy was commonly employed for the treatment of oesophageal cancer. High-grade nuclear pleomorphism in oesophageal carcinomas was correlated to chemo-responsiveness of the tumour. Four cancer cell lines were established from patients with oesophageal squamous cell carcinomas. These newly established cell lines serve as a useful model for studying the molecular pathogenesis, and testing new therapeutic reagents for oesophageal squamous cell carcinoma. Proliferative activity, as defined by the MIB-1 labelling index, was related to tumour differentiation in oesophageal squamous cell carcinoma. The activity was high in poorly-differentiated squamous cell carcinoma, basaloid squamous carcinoma and small cell carcinoma of the oesophagus. MIB-1 labelling index was found to be valuable as an independent prognostic marker in addition to tumour stage and size. Image analysis could assist h~ counting of the proliferative activity. Human papilloma virus was detected in a small proportion of oesophageal squamous cell carcinomas. There was no correlation between the prevalence of HPV and p53 mutation in these tumours. Epstein Barr virus was not detected in squamous cell carcinomas and mesenchymal tumours. The pattern of expression of cytokeratins in oesophageal carcinomas is different from that in normal oesophageal epithelia and varies with differentiation. Cancer-related genes studied in oesophageal cancers were p53, p21, c-erbB-2, PTEN and telomerase activity. p53 mutations were common in oesophageal squamous cell carcinomas and small cell carcinomas. The distribution of p53 mutations in oesophageal cancers suggests that the gene has complex exogenous and endogenous interactions. p53 mutations also appear to play a role in predicting the survival of patients with stage III oesophageal squamous cell carcinomas. The pattern of p21 and p53 expression predicts an aggressive clinical course of oesophageal squamous cell carcinomas. c-erbB-2 (Her-2) oncoprotein was expressed in a portion of oesophageal squamous cell carcinomas and precursor lesions. This suggests that c-erbB-2 activation plays a certain role, mostly probably during the early stages, in carcinogenesis. PTEN/MMAC1 mutations were not detected in oesophageal squamous cell carcinoma. Telomerase activation was common in small cell carcinoma and basaloid squamous cell carcinoma of the oesophagus. The level of telomerase activity had a prognostic role in oesophageal cancer, suggesting a possible therapeutic role of anti-telomerase treatment for this aggressive tumour. Multiple genetic mutations in oesophageal squamous cell carcinomas could be mapped by gene arrays and comparative genomic hybridization. These different newly discovered genetic alterations were analysed both in laboratory and in relationship with the clinical prognosis. Multiple mutations could be detected in dysplasia as well as carcinoma. The techniques identify the roles of some new cancer-related genes like Fra-1, Neogenin, Id-i, CDC2SB and MET in oesophageal squamous cell carcinomas. Chromosomal aberrations were common in oesophageal squamous cell carcinoma. Gain in l2p was found to be indicative of aggressive behaviour and poor prognosis. In summary, identification of the different histological types of oesophageal tumours and their characteristic molecular profiles is essential for both in-depth research and clinical management.