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E Kumpulainen

Publications and source records attributed to E Kumpulainen.

At least 19 recordsLinked to original sources

CD44 expression and its relationship with MMP-9, clinicopathological factors and survival in oral squamous cell carcinoma.

We investigated the expression of CD44 and MMP-9 in primary oral squamous cell carcinoma (OSCC) and evaluated their association with each other and clinicopathological factors as well as their prognostic value during long term follow up. Histological samples from 138 OSCC patients were immunohistochemically stained for the expression of CD44 and MMP-9. The staining results were compared with conventional prognostic factors and their impacts to patients' prognosis were also studied with survival analyses. Irregular staining of CD44 in tumour cells was associated with poor tumour differentiation (p=0.003), higher clinical stage (III-IV) (p=0.049), and the presence of T3-4 tumour stage (p=0.03). Strong stromal MMP-9 staining intensity was correlated with poor tumour differentiation (p=0.03). In univariate survival analysis irregular staining of CD44 in tumour cells was related to poor disease free and overall survival (p=0.001 and p<0.001, respectively). In multivariate analysis CD44 staining was a significant independent predictor for overall (p=0.03) and disease free survival (p=0.003). MMP-9 expression showed no statistical significance in survival analyses. Strong stromal staining intensity of MMP-9 correlated with irregular staining of CD44 in tumour cells, but had no prognostic significance in the present cohort. However, irregular staining of CD44 predicted more advanced disease and shortened survival of the patients.

Adolescent↗

Reduced expression of hyaluronan is a strong indicator of poor survival in oral squamous cell carcinoma.

Several malignant tumours accumulate hyaluronan (HA), a matrix component suggested to promote cancer cell growth and migration. The expression and prognostic value of HA was analysed in a cohort of 151 oral squamous cell carcinoma (SCC) patients with adequate archival tumour material and follow-up data. The tumour samples were stained using a biotinylated HA-specific probe. Normal squamous epithelium showed a strong and homogeneously distributed staining for HA. The most superficial layers were HA-negative. In moderate (n=11) and high grade (n=16) dysplasias an irregular HA staining was observed around invasive cancer. Malignant transformation in oral squamous cell epithelium changed the staining toward irregular with focal reduction of HA. The well (n=92) or moderately differentiated (n=47) carcinomas had a strong HA staining intensity. In poorly differentiated tumours (n=12) the HA staining was weaker and mainly intracellular. The stromal tissue showed usually moderate (n=69) or strong (n=67) HA staining intensity with no statistically significant correlation with the degree of tumour differentiation. At the end of the follow-up (median 52 months) 66 (43%) patients had died because of an oral SCC. A significant difference in overall survival (OS) and disease free survival (DFS) (P=0.0002 and 0.0020, respectively) was noticed between the patients with the different epithelial staining patterns for HA. The reduction of HA staining was associated with poor survival. In Cox's multivariate analysis HA staining was a significant independent predictor of OS (P=0.011) and DFS (P=0.013). These results suggest that HA is a prognostic marker in oral squamous cell carcinoma.

Adolescent↗

Bleomycin, vincristine, lomustine and dacarbazine (BOLD) in combination with recombinant interferon alpha-2b for metastatic uveal melanoma.

This EORTC multicentre study analysed the efficacy and tolerability in patients with metastatic uveal melanoma of BOLD chemotherapy in combination with recombinant interferon alpha-2b. The dose of bleomycin was 15 mg on days 2 and 5, of vincristine 1 mg/m(2) on days 1 and 4, of lomustine 80 mg on day 1, and of dacarbazine (DTIC) 200 mg/m(2) on days 1-5, given every 4 weeks for a minimum of two cycles. Subcutaneous (s.c.) interferon alpha-2b at a dose of 3 x 10(6) IU was initiated on day 8 of the first cycle, and continued at a dose of 6 x 10(6) IU three times per week after 6 weeks. A median of two cycles were administered to 24 patients (median age 60.5 years). None achieved an objective response (0%; 95% Confidence Interval (CI): 0-14), 2 (8.3%) remained stable, 20 showed progression, and 2 (8.3%) were invaluable. The median progression-free survival was 1.9 months (95% CI: 1.8-3.4) and overall survival 10.6 months (95% CI: 6.9-16.4). Overall survival improved with increasingly favourable pretreatment characteristics (median, 14.7 versus 6.9 versus 6.0 months for Helsinki University Central Hospital (HUCH) Working Formulation stages IVBa, IVBb and IVBc, respectively; P=0.018). Grade 3 alopecia and neurotoxicity occurred in 13% of the patients. This multicentre study did not confirm earlier reports that BOLD with human leucocyte or recombinant interferon would induce at least 15% objective responses in metastatic uveal melanoma.

Adult↗

Supraglottic and glottic carcinomas. clinically and biologically distinct entities?

This study aimed to examine the clinical and biological differences in 198 patients with either T1-T2 local glottic or supraglottic squamous cell carcinomas. The patients with supraglottic cancer had a poorer prognosis, as well as more advanced and histologically aggressive tumours than the patients with glottic tumours. They also had lower levels of haemoglobin and a poorer nutritional and performance status. Expression of alpha-catenin, hyaluronan, CD44, p53, p21/WAF1 and bcl-2 in the primary tumour were not associated with the site of the laryngeal carcinoma. In supraglottic tumours, the rate of spontaneous apoptosis and mitotic indices were significantly higher than in glottic tumours. The results suggest that clinical parameters including the haemoglobin level of the patient together with the tumour cell kinetics (mitotic and apoptotic rates) may contribute to the aggressive nature of supraglottic carcinoma.

Adult↗

Serum adhesion molecules and interleukin-2 receptor as markers of tumour load and prognosis in advanced cutaneous melanoma.

Cell adhesion molecules are cell surface glycoproteins that may act as mediators in the metastatic process. Soluble interleukin-2 receptor (sIL-2R) is an immunological marker that may also serve as an indicator of tumour progression. Normal and neoplastic cells are capable of releasing these molecules into circulation. We evaluated the association between pretreatment serum levels of soluble intercellular adhesion molecule 1 (sICAM-1), vascular cell adhesion molecule 1 (sVCAM-1) and sIL-2R and metastases and survival in 50 patients with advanced melanoma. The patients with liver and/or bone metastases had significantly higher sICAM-1 levels than those with soft tissue and/or lung involvement (P=0.002). In addition, there was a trend towards higher sIL-2R levels in patients with more metastatic sites (P=0.07). In univariate analysis, the number of metastatic sites (P=0.0001, odds ratio (OR) 3.0, 95% confidence interval (CI): 1.7-5.3), the metastatic site (P=0.01, OR 2.3, 95% CI: 1.2-4.4) and the levels of sICAM-1 (P=0.011, OR 2.5, 95% CI: 1.2-5.0), sVCAM-1 (P=0.036, OR 2.1, 95% CI: 1.0-4.3) and sIL-2R (P=0.0016, OR 3.0, 95% CI: 1.5-6.0) were found to be statistically significant prognostic factors for survival. In multivariate analysis, the number of metastatic sites was the dominant prognostic indicator. After it was excluded from the analysis, the sIL-2R level and the metastatic site were found to be significant. It can be concluded, that high sICAM-1 levels suggest liver metastases and sIL-2R seems to serve as a marker of tumour load in metastatic melanoma. Furthermore, the sIL-2R level appears to add to clinical data predicting the patient's outcome.

Adult↗

The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography.

PURPOSE: We studied which, age of the patient or density of the breast accounts for the sensitivity of mammography and ultrasonography (US). Furthermore we studied whether the overall impression on the density of the breast or the density in tumour area accounts for the sensitivity of mammography and ultrasonography. MATERIALS AND METHODS: The material consisted of 572 consecutive histologically and 5 cytologically verified breast cancer cases. Mammography and US examinations were performed immediately before breast cancer operations and information on the findings were received from the original patient files and classified as malignant or benign. The density of breast parenchyma to fatty, mixed or dense in total breast and separately in tumour area was defined by a radiologist group from the original mammograms by comparing to model mammograms. The sensitivity (Se) of mammography and US was compared in 3 age groups (26-49, 50-59 and 60-92) and in the different density classes. RESULTS: Sensitivity of mammography increased by age (density-adjusted OR = 0.2, 95%, CI 0.1-0.5) in age group 26-49 compared to age group 60-92) and with fattiness of the breast (age-adjusted OR= 0.4, 95%, CI 0.1-1.0 for dense breast parenchyma in tumour area compared to fatty breast). Sensitivity of US was inversely related to age (density-adjusted OR = 2.3, 95%, CI 1.0-5.2 in age group 26-49 compared to age group 60-92) and directly related with fattiness of breast (age-adjusted OR = 0.5, 95%, CI 0.2-0.9 by dense breast parenchyma in tumour area compared to fatty breast). Density in the tumour area compared to total breast density was related only mariginally better sensitivity both of mammography (0.4 vs. 0.6) and of US (0.5 vs. 0.6). CONCLUSION: Sensitivity of both mammography and sensitivity of US are independently related both to the age of the patient and to the density of the breast. The effect of age is inverse and that of density parallel between mammography and US on sensitivity. The effect of overall breast density was close to the effect of density at the site of the tumour on the sensitivity of both mammography and US.

Adult↗

The visibility of cancer on previous mammograms in retrospective review.

AIM: To study how many tumours were visible in restrospect on mammograms originally reported as normal or benign in patients coming to surgery with proven breast cancer. The effect of making the pre--operative mammogram available was also assessed. MATERIALS AND METHODS: Three hundred and twenty initial mammograms of consecutive new breast cancer cases were analysed by a group of radiologists in the knowledge that all patients were later diagnosed with breast cancer. The films were read twice, first without and then with the later (pre-operative) mammograms available. The parenchymal density in the location of the tumour was classified as fatty, mixed or dense, and the tumours were classified as visible or not visible. The reasons for the invisibility of the tumour in the earlier examination were analysed. RESULTS: Fourteen per cent (45) of cancers were retrospectively visible in earlier mammograms without the pre-operative mammograms having been shown, and 29% (95) when pre-operative mammograms were shown. Breast parenchymal density decreased with age and the visibility of tumours increased with age. When considered simultaneously, the effect of age (over 55 vs under 55) was greater (OR = 2.9) than the effect of density (fatty vs others) (OR = 1.5). The most common reasons for non-detection were that the lesion was overlooked (55%), diagnosed as benign (33%) or was visible only in one projection (26%). Growing density was the most common (37%) feature of those lesions originally overlooked or regarded as benign. CONCLUSIONS: Tumours are commonly visible in retrospect, but few of them exhibit specific signs of cancer, and are recognized only if they grow or otherwise change. It is not possible to differentiate most of them from normal parenchymal densities. Saarenmaa, I. (2001). Clinical Radiology56, 40-43.

Adult↗

Validity of radiological examinations of patients with breast cancer in different age groups in a population based study.

By studying which radiological examinations had been performed before breast cancer operations the aim was to assess, how much benefit ultrasonography (US) and fine or core needle biopsy (FNAB, CNB) gave in addition to mammography, and whether the sensitivity of these examinations varied with the age of the patient. There were 659 consecutive histologically and six cytologically verified breast cancer cases included in the study. Information on mammography, US and FNAB findings were retrieved from the original patient files and classified as malignant or benign. The sensitivity (Se) of these was compared in three age groups (26-49, 50-59 and 60-92). Seventeen (3%) tumours had operations without any radiological examination and 73 (11%) without cytological or histological verification. The sensitivity of mammography (Se=0.92) was statistically significantly higher than the sensitivity of FNAB (Se=0.85, P=0.002) or US (Se=0.86, P=0.003). The sensitivity of mammography increased with age; US sensitivity was slightly higher amongst younger than older patients; the sensitivity of FNAB did not depend on the age of the patient. The sensitivity using a cutoff level of class 5 for mammography was higher (50% typical malignant findings) than for US (45%) or FNAB (30%). Among cases with benign mammographic finding (classes 1-2), the US finding was malignant (classes 3-5) in 4% and FNAB was malignant in 7%. Mammography is a reliable method of breast examination especially for women over 50 years of age. Ultrasonography is beneficial, particularly in younger women, but it is mainly performed as a complementary examination to a mammography and therefore could not be evaluated as an independent examination. FNAB and CNB results were not related to the age of the patient.

Journal Article↗

Merkel cell carcinoma of the auricle.

Merkel cell carcinoma is a rare, although increasingly recognized, malignant tumor of the skin. The most common site of occurrence is the head and neck (50%). Only five cases of this tumor on the auricle have been reported previously. We present a further such case. The incidence, clinical features, diagnosis, prognosis, and treatment of the Merkel cell carcinoma are discussed.

Aged↗

Serum matrix metalloproteinase-2 as a prognostic marker in advanced cutaneous melanoma.

The association was studied between serum concentration of matrix metalloproteinase-2 (MMP-2) and metastatic site, survival and disease progression in patients with advanced cutaneous melanoma. The patient population consisted of 50 patients who were treated with chemoimmunotherapy. The median baseline serum concentration of MMP-2 was 724 ng/ml (range 500-2,297 ng/ml). There were no significant differences in MMP-2 levels according to metastatic site. Baseline MMP-2 concentration did not have a prognostic value. The patients with levels below 800 ng/ml survived for 8.8 months and those with higher levels for 9.7 months. On serial measurements, median serum MMP-2 concentration at disease progression in 25 patients was significantly higher than before treatment. Only five samples at response were available, and the levels were not significantly different from baseline levels. In conclusion, serum MMP-2 is not a prognostic marker in advanced melanoma. It also appears to be of limited clinical value in monitoring.

Adult↗

The value of serum S-100beta and interleukins as tumour markers in advanced melanoma.

Recently serum S-100beta has shown promise as a tumour marker in melanoma; however, its use as a prognostic marker in the advanced stage needs to be confirmed. Interleukins (ILs) may mediate regression or progression of cancer. In order to study their relation to the metastatic profile and survival, we evaluated the association between pretreatment serum levels of S-100beta, IL-6, IL-10 and IL-12 and metastatic site and survival in 50 patients with advanced melanoma who were to receive chemoimmunotherapy. Patients with liver and/or bone metastases had significantly higher median concentrations of S-100beta, IL-6 and IL-10 than those with only skin, nodal and/or lung involvement. The differences in IL-12 levels were unremarkable. Using univariate analysis, the S-100beta level and metastatic profile were found to be statistically significant prognostic factors for survival. Using multivariate analysis the S-100beta level was the most powerful prognostic indicator, while the metastatic profile was found to be significant after exclusion of S-100beta. The findings suggest that elevated serum levels of S-100beta, IL-6 and IL-10 reflect concurrent liver or bone metastases in melanoma. S-100beta is also an independent prognostic marker. Pretreatment IL levels were not associated with outcome.

Adult↗

Irregular expression of hyaluronan and its CD44 receptor is associated with metastatic phenotype in laryngeal squamous cell carcinoma.

The distributions of hyaluronan (HA) and its CD44 receptor were studied in 24 normal, 27 dysplastic samples of laryngeal epithelium and in 172 squamous cell carcinomas (LSCC), using a specific probe prepared from cartilage proteoglycan (bHABC, biotinylated hyaluronan binding complex) and a monoclonal antibody (Hermes 3). HA and CD44 were expressed similarly in all normal and about 90% of dysplastic and neoplastic laryngeal epithelia. In the normal epithelium HA and CD44 were homogeneously distributed throughout the epithelium, whereas the most superficial layers were negative. This was in contrast to the picture in dysplastic epithelium and well-differentiated invasive carcinomas, which were entirely HA and CD44 positive. Local areas with a low signal for HA and CD44 were present in 11% and 22% of the samples with dysplasia, and in 27% and 28% of those with carcinoma, respectively. The presence of this staining irregularity was associated with poor differentiation of the carcinoma, a significantly elevated mitotic index and a high frequency of nodal spreading and metastases. Furthermore, the irregular staining showed a trend towards poor disease-free survival, suggesting that an altered metabolism of HA is a common feature in LSCC and is associated with an aggressive growth pattern.

Carcinoma, Squamous Cell↗

The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer.

An established biochemical index for monitoring therapy in patients with metastatic breast cancer was tested prospectively in a multicentre study. The index uses two serum tumour markers--carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR). 67 patients treated by either endocrine or chemotherapy had CA15-3, CEA and ESR measured at diagnosis of metastases and sequentially during therapy. Two markers, CA15-3 and CEA, were measured on a further 16 patients giving a total of 83 patients who were assessable for CA15-3 and CEA. Of the patients with CA15-3, CEA and ESR measured at diagnosis of metastases 84% (56/67) had elevation of 1 or more markers. During therapy the number with elevated marker(s) rose to 96% (64/67). Changes in the markers were in line with and often pre-dated therapeutic outcome as assessed by the International Union Against Cancer (UICC) criteria both for remission and progression. Patients without elevation of markers on diagnosis subsequently showed a rise in the marker(s) at or before documented disease progression by UICC. The 3 women in whom markers were at no time significantly elevated remain in remission. The results using CA15-3 and CEA were similar but 12% less patients were assessable. CA15-3 and CEA (with and without ESR) provide an objective method to guide therapy in patients with metastatic breast cancer.

Antigens, Tumor-Associated, Carbohydrate↗

Enhanced apoptosis correlates with poor survival in patients with laryngeal cancer but not with cell proliferation, bcl-2 or p53 expression.

The purpose of the current study was to analyse apoptosis and bcl-2 expression in laryngeal squamous cell carcinoma (SCC) with special reference to their prognostic significance, correlation with the clinical and pathological characteristics as well as cell proliferation and p53 accumulation. 172 patients with primary laryngeal SCC were followed-up for a median of 67 months. The volume corrected apoptotic (A/V) index was analysed using an in situ end labelling method (TUNEL) in 85 randomly selected patients. The expression of bcl-2 and p53 was analysed with monoclonal antibodies. The proliferative activity was measured both with Ki-67 (MIB-1) antibody and the volume corrected mitotic (M/V) index. The A/V index was not associated with p53 (P = 0.6) or bcl-2 (P = 0.6) expression or with proliferative parameters (P = 0.9 for M/V and P = 0.3 for MIB-1). The 10-year overall survival in patients with a high A/V index was poorer when compared with patients with a low index (47% versus 81%, P = 0.005), while accumulation of bcl-2 had no prognostic significance (P = 0.5). In Cox multivariate analysis of the whole cohort, stage (P < 0.0005) and histological grade (P = 0.04) were predictors of overall survival. In the subset of patients with an A/V index available, predictors of survival were stage (P = 0.05), A/V index (P = 0.02) and histological grade (P = 0.04). A high A/V index was an independent predictor of poor survival in laryngeal SCC. This effect was not associated with tumour cell proliferation. Accumulations of p53 and bcl-2 were not associated with apoptosis. Expression of bcl-2 lacks any prognostic significance in laryngeal SCC. We propose that assessment of the A/V index may help in selecting patients with poor prognosis.

Adult↗

Long-term mental health outcome of returning migrant children and adolescents.

We examined how remigration influences the prevalence of psychiatric symptoms among children and adolescents in the long term. We investigated depressive and behavioral symptoms in 320 Finnish children and adolescents who moved back from Sweden while of school-age during the years 1984-1985 and in a series of controls. The data were gathered in two phases, with questionnaires sent to the parents, children and teachers in 1986, and with further questionnaires sent to the parents and children in 1992. Depression was measured by means of the Children's Depression Inventory (CDI) (8) and behavioral symptoms with the Children's Behavioral Questionnaire, filled in by the teachers (14) in the first phase and by the parents (15) in the second. We compared prevalence of these psychiatric symptoms between the migrants and controls in groups divided by age and sex in the two phases and examined how depressiveness or behavioral disturbance shortly after migration served to predict later psychiatric symptoms. The following findings emerged: The boys who moved before puberty had more psychiatric symptoms than their controls in both phases, while the best-adapted group consisted of the girls who moved before puberty. Those migrant children who moved during puberty had more psychiatric symptoms than their controls only in the second phase. The depressive features and behavioral disturbances observed among the migrants during the first phase did not lead to disturbances in the second phase, whereas an association was found between psychiatric disturbances among the native controls in the first and second phases.

Adaptation, Psychological↗

p53 expression and cell proliferation as prognostic factors in laryngeal squamous cell carcinoma.

PURPOSE: To investigate the prognostic significance of p53 expression and proliferation markers in primary laryngeal squamous cell carcinoma. PATIENTS AND METHODS: Primary tumors for analyses were obtained from 103 patients, with complete follow-up data. All patients were treated between the years 1975 and 1990. The expression of p53 was analyzed with monoclonal D07 antibody and proliferative activity with Ki-67 (MIB-1) and PCNA (monoclonal 19A2) antibodies. Volume corrected mitotic (M/V) index and histological grade were determined in hematoxylin and cosin-stained slides. RESULTS: Sixty-eight percent of the tumors overexpressed p53. During a median follow-up of 62 months, 41 (40%) of patients relapsed. In univariate analysis site of the primary tumor, stage, p53 expression, histologic grade, and M/V index were significant predictors of disease-free survival. In multivariate analysis, only M/V index was a statistically significant predictor of disease-free survival. Overall survival was significantly better for those overexpressing p53 (10-year cumulative survival rate 68% v 44%, P = .004). In multivariate analysis, M/ V index (P = .02), p53 (P = .02), and stage (P = .007) were statistically significant predictors of overall survival. When this analysis includes stratification according to the type of treatment received, M/V index (P = .007), stage (P = .0002), and p53 (P = .006) were even more significant predictors of overall survival. No association between p53 status and proliferative activity was found. CONCLUSION: Overexpression of p53 is associated with favorable disease-free and overall survival in laryngeal squamous cell carcinoma. It may also have an independent prognostic value in laryngeal cancer. M/V index, p53 overexpression, and stage predict with significant accuracy the 10-year overall survival.

Adult↗