Abstract
Aptosis denotes a biochemically and morphologically distinct
chain of events leading to self-destruction of cell. It is pivotal
in the maintenance of tissue homeostasis and also plays a role in neoplasm.
In this work, the extent of apoptosis and apoptosis regulating proteins
and factors was studied in a total of 94 patients operated for lung
carcinoma, including 56 small cell lung carcinomas (SCLC) and 38
large cell lung carcinomas (LCLC). The extent of apoptosis was determined
by detecting and counting the relative and absolute numbers of apoptotic
cells and bodies using 3'- end labelling of the apoptotic
DNA. The extent of apoptosis in SCLC was compared with the cell proliferation
activity as determined by Ki-67 immunohistochemistry, with the volume
density of necrosis and with the occurrence of immunohistochemically
detectable p53 and bcl-2 proteins. In order to test the hypothesis
that increased apoptotic activity is connected with neuroendocrine differentiation
and with low differentiation degree in LCLC and that it is regulated
by bcl-2 family proteins, the extent of apoptosis and tumour necrosis
was analysed in relation to the expression of bcl-2 family proteins
bcl-2, mcl-1, bax and bak. Apoptosis, tumour infiltrating lymphocytes
(TILs), and angiogenesis are important factors that contribute to
tumour growth. In the present study immunohistochemical methods
were used to investigate the relationships of these factors and
their role in the prognosis of the patients with LCLC and SCLC.
A remarkably high apoptotic activity was detected in both
SCLC and LCLC. The mean apoptotic index in SCLC was 2.70 % and
in LCLC 2.49 %. Exceptionally high proliferation activity
and high percentage of tumour necrosis was seen in SCLC. 58 % of
SCLC showed more than 40 % of Ki-67 positive nuclei, and
tumour necrosis was seen in 83 % of the cases. P53 protein
accumulation was detected in 38 % and bcl-2 expression
in 50 % of SCLC. The extent of apoptosis in SCLC was inversely
related to tumour necrosis and p53 protein accumulation. In LCLC,
bcl-2 expression was detected in 40 % of the cases. It
was associated with neuroendocrine differentiation and predicted favourable
prognosis of the patients. A high number of T cells and macrophages
with a small number of B cells was detected in both SCLC and LCLC.
The occurrence of intratumoural cytotoxic CD8 cells was associated
with the occurrence of apoptotic bodies in SCLC. The increased number
of intratumoural T cells, CD8-positive cells and macrophages predicted
favourable prognosis of the patients with SCLC. In LCLC, an increased
number of B cells and macrophages, but not T cells, was associated
with better survival.
Iaddition to tumour cells, numerous apoptotic bodies could
also be found within alveolar macrophages within and close to tumour
tissue. In order to test whether such cells could be found in sputum
smears and if their presence could be utilised as a marker of malignancy
in tumour diagnosis, the occurrence of alveolar macrophages with
apoptotic bodies (AMWABs) was analysed in 84 sputum samples and
13 broncho-alveolar lavage (BAL) specimens from patients with and
without lung carcinoma. AMWABs could be found in cytological samples
of the patients with lung carcinoma. In sputum and BAL specimens,
enhanced apoptosis, as measured by an increased number of AMWABs
reflected and was indicative of malignancy. This was also true for
cytological specimens of the patients even when the actual malignant
cells were not found. Therefore the AMWABs served as a marker of
pulmonary malignancy.
| Identifer | oai:union.ndltd.org:oulo.fi/oai:oulu.fi:isbn951-42-5406-6 |
| Date | 30 September 1999 |
| Creators | Eerola, A.-K. (Anna-Kaisa) |
| Publisher | University of Oulu |
| Source Sets | University of Oulu |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/doctoralThesis, info:eu-repo/semantics/publishedVersion |
| Format | application/pdf |
| Rights | info:eu-repo/semantics/openAccess, © University of Oulu, 1999 |
| Relation | info:eu-repo/semantics/altIdentifier/pissn/0355-3221, info:eu-repo/semantics/altIdentifier/eissn/1796-2234 |
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