| 1. |
- Borgfeldt, Christer, et al.
(author)
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Dedifferentiation of serous ovarian cancer from cystic to solid tumors is associated with increased expression of mRNA for urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor (PAI-1)
- 2001
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 92:4, s. 497-502
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Journal article (peer-reviewed)abstract
- The plasminogen activating system is involved in tumor growth and metastasis by degradation of extracellular matrix, and modulation of cell adhesion and migration. Benign and well-differentiated malignant ovarian tumors present as cystic lesions with preserved glandular morphology, whereas poorly differentiated tumors and metastases are solid with characteristic absence of glandular morphology. We analyzed the mRNAs for urokinase plasminogen activator (uPA), its receptor (uPAR), and inhibitor (PAI-1) in serous ovarian tumors by in situ hybridization and by densitometric scanning of Northern blots prepared from tissue extracts. The mRNA expressing cells in the in situ hybridization sections were evaluated and counted by two different observers. The number of mRNA expressing cells for uPA, uPAR and PAI-1 were all significantly increased in solid as compared with cystic malignant tumors. The increased expression of all three mRNA species was mainly located in the stroma of poorly differentiated tumors and metastases. Apart from being expressed in the stroma of these tumors, uPAR mRNA was also expressed by tumor cells located along the stromal/epithelial boarder. In addition, the tumor tissue content of uPA, uPAR and PAI-1 mRNAs as measured by Northern blots were higher in the solid as compared with the cystic tumors. Increased expression of uPA, uPAR and PAI-1 genes in the solid tumors suggest a correlation with a more aggressive phenotype.
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| 2. |
- Måsbäck, Anna, et al.
(author)
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Clinical and histopathological features of malignant melanoma in germline CDKN2A mutation families
- 2002
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In: Melanoma Research. - 0960-8931. ; 12:6, s. 549-557
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Journal article (peer-reviewed)abstract
- Primary cutaneous malignant melanomas (CMMs) from 26 individuals belonging to nine families with an identified CDKN2A mutation were clinically and histopathologically compared with 78 matched CMM controls and with a population-based series of CMMs (n=667). All tumours were histopathologically re-examined. CDKN2A-associated cases were significantly less invasive compared with the matched controls, with an adjusted odds ratio (adjOR) of 2.9 and a 95% confidence interval (CI) of 1.0-8.1 (P=0.04). According to the odds ratio (OR) values, CDKN2A-associated cases seemed to have tumours more often located on the head and neck (adjOR 2.9, 95% CI 0.6-13.7), with less inflammation (adjOR 0.7, 95% CI 0.3-1.8) and regression (adjOR 0.6, 95% CI 0.2-1.8) but more frequent histological ulceration (adjOR 1.9, 95% CI 0.6-5.8). In comparison with the population-based material, CDKN2A-associated cases were significantly younger at diagnosis (crude OR 3.5, 95% CI 1.6-7.5, divided at 50 years) and had less regressive reaction in their tumours (crude OR 0.355 95% CI 0.2-0.8). No significant differences were seen for tumour thickness between the different groups. On multivariate analysis, the overall survival was significantly worse for thicker tumours and older age (P=0.04 for both). To our knowledge this is the first description of the histopathological features of CMMs from families with mutations in the CDKN2A gene.
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| 3. |
- Måsbäck, Anna
(author)
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Malignant Melanoma in southern Sweden; Histopathology, Prognosis and Aetiology
- 2002
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Doctoral thesis (other academic/artistic)abstract
- The purpose was to study the prognostic and aetiologic risk factors for melanoma in correlation to histopathology. Paper 1-3: Thin tumours (<0.8 mm), tumours with inflammation and median age at diagnosis were signifcantly increasing in 711 CMM patients during the period 1965-89. No difference was found in median thickness. Factors that significantly improved prognosis were; thin tumour thickness, absence of ulceration, female gender, tumour location on extremities, young age and moderate/much tumour inflammation. Correlations between different factors were found, e.g. tumour localisation predominating on the back in males and on the legs in females. LMM (Lentiginous Malignant Melanoma) was seen in combination of old age and facial tumour site. Further there was a relation between thicker tumours and deeper invasion, nodular type (NM), ulceration and older age. Tumours with inflammation were related to thinner tumours, younger age, male sex, location on non-extremities and absence of naevus cells. Paper 4: In a case-control study including 366 CMM patients, a history of melanoma in the family was significantly related to thin tumours (<0.8 mm), tumour site on the trunk and non-significantly associated to younger age at diagnosis. Further the risk for developing SSM-type was significantly increased with the tendency to freckle, raised naevi, propensity to sunburn and decreased with out-door occupation. The NM-type was associated with the presence of raised naevi on the forearm and to sunburn. Absence of naevus cells in the tumour had a significant correlation to sunburn and the presence of raised naevi. Paper 5: From families with CDKN2A-mutation 26 CMM patients were identified and matched with each 3 controls. The invasive level according to Clark was significantly lower among cases compared to controls. No significant differences were seen for tumour thickness. Compared to a population-based material (n=667), cases were significantly younger at diagnosis (median age 42 vs. 61 years) and had less regressive reaction in their tumours.
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| 4. |
- Måsbäck, Anna, et al.
(author)
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Prognostic factors in invasive cutaneous malignant melanoma: a population-based study and review
- 2001
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In: Melanoma Research. - 0960-8931. ; 11:5, s. 435-445
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Journal article (peer-reviewed)abstract
- A population-based study from Sweden identified 711 patients with cutaneous malignant melanoma diagnosed in 1965, 1975, 1985 and 1989. Prognostic factors were evaluated and a review of the literature was performed. On univariate analysis, thick tumours (> 0.8 mm) (odds ratio [OR] 1.8, 95% confidence interval [CI] 1.6-2.1), increasing Clark level (OR 1.8, 95% CI 1.6-2.0), ulceration (OR 1.8, 95% CI 1.6-2.0), nodular melanoma (OR 1.5, 95% CI 1.3-1.6) and increasing age (continuous variable, P < 0.0001) were associated with a shorter survival. Location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-0.9) were associated with improved survival. On multivariate analysis, thick tumours (> 0.8 mm) (OR 1.5, 95% CI 1.2-1.7) and ulceration (OR 1.4, 95% CI 1.2-1.6) were independently related to a poor prognosis, while location on extremities (OR 0.8, 95% CI 0.7-0.9), inflammation (OR 0.8, 95% CI 0.7-0.9) and female gender (OR 0.8, 95% CI 0.8-1.0) were associated with improved survival. No difference in mean tumour thickness was seen over time, but there was a significant increase in the percentage of thin melanomas (< 0.8 mm) in 1985 (P = 0.01) and 1989 (P = 0.002) compared with 1965. The incidence of melanomas with inflammation increased significantly (P = 0.04), as did age at diagnosis (P = 0.005).
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