PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 10651312

Thymidine phosphorylase expression in endometrial carcinomas.

E Sivridis·A Giatromanolaki·M I Koukourakis·R Bicknell·A L Harris·K C Gatter
View original source ↗Export metadata ↓

Abstract

Thymidine phosphorylase (TP) is a potent angiogenic molecule shown to induce endothelial cell migration and proliferation. We investigated the expression of TP in a series of 156 endometrial carcinomas, using immunohistochemical methods. Histopathological parameters of known prognostic significance and the molecular factors of p53, bcl-2 and angiogenesis were also assessed. Thymidine phosphorylase was expressed in cancer cells, stromal fibroblasts and myometrial cells. The pattern of TP staining was nuclear or mixed nuclear/cytoplasmic, and only exceptionally was purely cytoplasmic. An exclusively cytoplasmic staining was documented for the tumour-associated foamy macrophages. Cancer cell reactivity was rather limited; only 3.2% of endometrial carcinomas expressed TP in more than 50% of the neoplastic cell population and only 12% expressed the enzyme in more than 10% of the cancer cells. By contrast, TP reactivity was frequent in the fibroblasts of the tumour supporting stroma and the fibroblasts/myometrial cells at the invading tumour front, where approximately 1/3 of the cases expressed TP in more than 50% of the respective constituent cells. A high TP reactivity in the stromal fibroblasts was significantly associated with the presence of foamy macrophages and an intense lymphocytic response. A high TP reactivity at the invading tumour front was significantly associated with an intense lymphocytic response and the adverse prognostic parameters of high tumour grade, deep myometrial invasion, advanced stage of disease and the non-endometrioid carcinomas. There was no significant association of cancer cell TP reactivity with any of the parameters studied, including nuclear p53 accumulation, cytoplasmic/perinuclear bcl-2 expression, microvessel density (MVD) and prognosis. Similarly, no relationship was established between fibroblastic or fibroblastic/myometrial TP reactivity and MVD. It is concluded that TP is not a major angiogenic factor in endometrial carcinomas. However, a prominent TP activity at the invading tumour front, which is probably induced by cytokines of histiocytic and lymphocytic origin, may promote tumour invasion and progression.

Explore related subjects

Endometrial NeoplasmsFemaleFibroblastsHumansMacrophagesThymidine PhosphorylaseJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

E Sivridis, A Giatromanolaki, M I Koukourakis, R Bicknell, A L Harris, K C Gatter. 1999. Thymidine phosphorylase expression in endometrial carcinomas.. https://doi.org/10.1023/a%3A1006603709248

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2007

Molecular genetic defects in endometrial carcinomas: microsatellite instability, PTEN and beta-catenin (CTNNB1) genes mutations.

PURPOSE: The present study aims to assess the incidence of microsatellite instability (MSI) and mutations in the PTEN and beta-catenin (CTNNB1) genes in endometrial carcinomas and to analyze the detected defects in these factors in relation to each other and to the clinico-pathological features of tumors. MATERIALS AND METHODS: In a series of 56 endometrioid endometrial carcinomas, the status of MSI was determined using nine polymorphic markers, and mutations in all exons of the PTEN gene and in exon 3 of the CTNNB1 gene were evaluated by SSCP and sequencing methods. RESULTS: Microsatellite instability was found in 18 carcinomas (32.1%, MSI+); the remaining 38 tumors were microsatellite stable (MSI-). In 15 cases (26.8%), a loss of heterozygosity (LOH) at the studied microsatellite markers also occurred. In 29 carcinomas (51.8%), mutations were found in the PTEN gene and in nine tumors (16.1%) in the CTNNB1 gene. PTEN mutations occurred significantly more frequently in MSI+ than in MSI- tumors (77.8 vs. 39.5%, p = 0.007), but, except for one, none of them was attributable to MSI. In contrast, incidence of CTNNB1 mutations in MSI+ and MSI- tumors no significantly differed between themselves (16.7 vs. 15.8%, p = 0.760). Interestingly, mutations in the CTNNB1 gene most frequently coexisted with mutations in the PTEN gene (7/9, 77.8%). However, this finding requires future verification on a larger group of cases. The incidence of MSI and PTEN, but not CTNNB1 mutations, was significantly more common in poorly, than in well-to-moderately, differentiated tumors (G3 vs. G1 + G2; p = 0.042, 0.039 and 0.958, respectively). CONCLUSION: We conclude that most frequently occurring mutations in the PTEN gene may be a key event for the tumorigenesis of endometrioid endometrial carcinomas, while coexistence or absence of microsatellite instability or mutations in the CTNNB1 gene may reflect the heterogeneity of molecular mechanisms contributing to the development of these tumors.

Endometrial Neoplasms↗
PubMed2007

Physical activity and endometrial cancer risk: a review of the current evidence, biologic mechanisms and the quality of physical activity assessment methods.

OBJECTIVES: To (1) determine the nature of the association between physical activity and endometrial cancer risk; (2) assess the contribution of variation in the quality of physical activity measurement to inconsistencies in study results; and (3) review the biologic mechanisms that might mediate possible effects of physical activity on risk. METHODS: We reviewed and summarized all published epidemiologic studies examining physical activity and endometrial cancer risk, and evidence relating to possible biologic mechanisms. We assigned each study a quality score for physical activity measurement. RESULTS: Fourteen of the 18 studies showed a convincing or possible protective effect of physical activity on endometrial cancer risk, with an average relative risk reduction of around 30%. A dose-response relation was observed in 7 of 13 studies. The quality score was not related to the observed strength of association or the presence of a dose-response relation. There was epidemiologic and biologic evidence that vigorous activity, as well as light and moderate intensity activities, such as housework, gardening or walking for transportation, may reduce risk. CONCLUSIONS: Physical activity probably has a protective role in endometrial cancer development. More epidemiologic and biologic evidence is needed to make conclusive recommendations on optimal types, characteristics or time periods of physical activity.

Endometrial Neoplasms↗
PubMed2007

Immunoprofile of endocervical and endometrial stromal cells and its potential application in localization of tumor involvement.

To evaluate and compare the immunophenotype of endocervical and endometrial stromal cells and to asses its potential application in tumor localization. Paraffin sections of benign endocervix (n = 24), benign endometrium (n = 33), endocervical adenocarcinoma (n = 9), endometrial carcinoma (n = 13), and endometrial hyperplasia (n = 16) were stained with antibodies to CD10, Wilms Tumor-1, CD34, smooth muscle actin, and factor XIIIa by immunohistochemistry. In 16 cases, lower uterine segment was also available. Immunoreactivity of stromal cells was recorded as positive (>/=50% staining), focally positive (>/=5%-<50%) or negative (<5%). Endocervical stromal cells (ECSC) in either benign or malignant cervical epithelial lesions were predominantly CD34/CD10 (CD34 dominant immunophenotype). Endometrial stromal cells (EMSCs) in either benign or malignant epithelial lesions were primarily CD34/CD10 (CD10 dominant immunophenotype). Expression of Wilms Tumor-1 was decreased in EMSC of the EMCA when compared to their counterpart in endometrial hyperplasia. There was no differential expression of smooth muscle actin and factor XIIIa identified between ECSC and EMSC. The immunophenotypes of the ECSC and EMSC overlapped in the lower uterine segment. The functional status of the endometrium had no effect on the immunoprofile. The pattern of CD34 and CD10 immunostaining in stromal cells might be helpful in determining tumor involvement in uterine and cervical sites.

Endometrial Neoplasms↗