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Tumour growth fraction and apoptosis in salivary gland acinic cell carcinomas: Prognostic implications of Ki-67 and bcl-2 expression and of in situ end labelling (TUNEL)
Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Reconstruction Centre, Department of ENT - Head and Neck Surgery UHL.
Department of Pathology and Laboratory Medicine, European Institute of Oncology, Milan University School of Medicine, Milan, Italy.
Linköping University, Department of Clinical and Experimental Medicine, Oto-Rhiono-Laryngology and Head & Neck Surgery . Linköping University, Faculty of Health Sciences.
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1997 (English)In: The Journal of Pathology, ISSN 0031-3025, Vol. 181, no 3, 323-329 p.Article in journal (Refereed) Published
Abstract [en]

bcl-2 protein and Ki-67 (MIB-1) were studied in 32 acinic cell carcinomas (ACCs), all with a minimum of 5 years' clinical follow-up. Tumour apoptosis was evaluated by TdT dUTP nick end labelling (TUNEL) and by morphological criteria. Five patients died of their disease. Patients with stage I tumours had significantly better survival compared with other stages (P<0·05). Patients with MIB-1-negative tumours had significantly better survival than patients with MIB-1-positive tumours (P=0·05). This study confirms a previous report that MIB-1 is an independent prognostic factor for survival in patients with ACC. Stage I tumours had high expression of bcl-2 protein, but there was no difference when compared with other stages. TUNEL positivity was most prevalent in stage I tumours, compared with stages II, III, and IV (P<0·05), probably indicating more apoptosis. This could imply a capacity of stage I tumours ('early tumours') for early selection of tumour cells for elimination by apoptosis. There was no significant difference between expression of bcl-2 and TUNEL, between these parameters and clinical outcome, or between any parameter and morphological subclassification. We conclude that MIB-1 has prognostic value in ACC. Clinical staging, bcl-2, and TUNEL are also potentially useful as prognostic markers.

Place, publisher, year, edition, pages
1997. Vol. 181, no 3, 323-329 p.
Keyword [en]
apoptosis, bcl-2, TUNEL, end labelling, salivary neoplasm, Ki-67
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-12804DOI: 10.1002/(SICI)1096-9896(199703)181:3<323::AID-PATH780>3.0.CO;2-KOAI: oai:DiVA.org:liu-12804DiVA: diva2:17089
Available from: 2007-11-28 Created: 2007-11-28 Last updated: 2009-08-18
In thesis
1. Head and Neck Cancer: Factors Affecting Tumour Growth
Open this publication in new window or tab >>Head and Neck Cancer: Factors Affecting Tumour Growth
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Head and neck cancer is the fifth most common cancer worldwide with an estimated annual global incidence of over 500 000 cases. These malignant tumours develop in the mucosal linings of the upper respiratory tract or in the salivary glands. The most common sites are in the oral cavity and larynx. Treatment modalities comprising surgery and chemoradiotherapy have improved significantly during the last 20 years, but not the long-term survival of patients. The aim of this thesis was to study the different factors affecting tumour growth in head and neck cancer that may have clinical implications in the future. Factors involving apoptosis, cell cycle activity, inflammation, and enzyme activity were of special interest.

The results of the thesis indicate that patients with malignant salivary gland tumours having the lowest level of actively replicating cells have the best prognosis. The largest amount of replicating cells in tongue cancer specimens was found in the peripheral areas of tumour nests. Metallothionein, a protein that can hinder apoptosis, was found in excess in the same areas, whereas apoptosis activity was considerably lower. Taken together, these results indicate that the most aggressive cancer cells are found in the peripheral areas of tumours where apoptosis may be hindered.

The expression of the death receptor Fas was higher in tongue cancer specimens than in normal mucosa. The expression of this receptor was studied further in two cell lines established from oral cancers. When a low dose of cisplatin was added to cell cultures, the Fas expression was enhanced in both cell lines and, furthermore, the Fas-induced apoptosis was increased in one of the cell lines. The results show that a common chemotherapeutic drug given in a low, less toxic dose may enhance receptor-mediated apoptosis of cancer cells.

Malignant solid tumours are often distinguished by an increased proteolytic activity resulting in invasive growth, neo-angiogenesis, and metastases. This activity is conducted by enzymes that are secreted from tumour cells, or from normal cells in the tumour microenvironment. The regulation of enzyme secretion may be mediated by cytokines, small signalling molecules also present in cancer tissue. The results of this thesis show that two cytokines can synergistically induce enzyme secretion (matrix metalloproteinase-1 and -9) from oral cancer cells. Cytokine tumour necrosis factor-alpha and hepatocyte growth factor added alone to cell cultures strongly stimulated secretion of these enzymes. Thus, the tested cytokines, which are commonly secreted by fibroblasts and immune cells, may promote tumour growth.

This thesis has contributed to an increased understanding of factors affecting tumour growth in head and neck cancer. The upcoming cancer therapies will be based on the increasing knowledge of these and other aberrant cellular mechanisms that may vary between different cancer forms.

Place, publisher, year, edition, pages
Institutionen för klinisk och experimentell medicin, 2007. 54 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1032
Keyword
Head and neck cancer, Chemoradiotherapy, Tumour, Malignant salivary, Metallothionein, Neo-angiogenesis, Metastases, Cytokine tumour necrosis factor-alpha, hepatocyte growth factor
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-10348 (URN)978-91-85895-31-1 (ISBN)
Public defence
2007-12-07, S. Entrén (Ingång 1), Universitetssjukhuset, Campus US, Linköpings universitet, Linköping, 13:00 (English)
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Available from: 2007-11-28 Created: 2007-11-28 Last updated: 2017-08-30

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Sundelin, KaarinaTytor, Maria

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Oto-Rhiono-Laryngology and Head & Neck Surgery Faculty of Health SciencesDepartment of ENT - Head and Neck Surgery UHL
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